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Scientia Pharmaceutica
Journal Prestige (SJR): 0.268
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  This is an Open Access Journal Open Access journal
ISSN (Print) 0036-8709 - ISSN (Online) 2218-0532
Published by MDPI Homepage  [246 journals]
  • Sci. Pharm., Vol. 90, Pages 57: A Narrative Review on the Bioactivity and
           Health Benefits of Alpha-Phellandrene

    • Authors: Subramanian Thangaleela, Bhagavathi Sundaram Sivamaruthi, Periyanaina Kesika, Tanawat Tiyajamorn, Muruganantham Bharathi, Chaiyavat Chaiyasut
      First page: 57
      Abstract: Aromatic essential oils play a significant role in pharmaceuticals, food additives, cosmetics, and perfumery. Essential oils mostly comprise aliphatic hydrocarbons, monoterpenoids, sesquiterpenoids and diterpenes. Plant extracts comprise a complex mixture of terpenes, terpenoids, aliphatic and phenol-derived aromatic components. Terpenes are a significant class of hydrocarbons with numerous health benefits. These biological functions of essential oil components are examined in vitro and in vivo studies. Some studies evaluated the properties and functions of α-phellandrene (α-PHE). Detailed evaluation to determine the functions of α-PHE over a spectrum of health care domains needs to be initiated. Its possible mechanism of action in a biological system could reveal the future opportunities and challenges in using α-PHE as a pharmaceutical candidate. The biological functions of α-PHE are reported, including anti-microbial, insecticidal, anti-inflammatory, anti-cancer, wound healing, analgesic, and neuronal responses. The present narrative review summarizes the synthesis, biotransformation, atmospheric emission, properties, and biological activities of α-PHE. The literature review suggests that extended pre-clinical studies are necessary to develop α-PHE-based adjuvant therapeutic approaches.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-09-27
      DOI: 10.3390/scipharm90040057
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 58: Retinoic Acid Potentiates the Therapeutic
           Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against
           Cisplatin-Induced Hepatotoxicity in Rats

    • Authors: Azzam, Hussein, Marghani, Barakat, Khedr, Heakel
      First page: 58
      Abstract: (1) Background: Hepatotoxicity is a common health problem, and oxidative stress plays a crucial role in its underlying mechanisms. We inspected the possible effect of retinoic acid (RA) in the potentiation of hepatoprotective effect of bone marrow mesenchymal stem cells (BM-MSCs) against Cisplatin (Cis)-induced hepatotoxicity. (2) Methods: 60 male Sprague Dawley rats (SD) were separated randomly and designated to six main equal groups as follows: (1) Control group, (2) Cis group (rats got Cis 7 mg/Kg i.p.), (3) Cis + vehicle group (as group 2, but rats received the (vehicle) culture media of BM-MSCs), (4) Cis as in group 2 + BM-MSCs (1x106), (5) Cis as for group 2 + RA 1 mg/Kg i.p., and (6) Cis and BM-MSCs as for group 3 + RA as for group 4. Liver injury was assessed by measuring liver enzymes (ALT, AST), while liver toxicity was evaluated by histopathological examination. Apoptotic marker caspase-3 protein was detected immunohistochemically. Real time PCR was performed to detect NADPH oxidase and TNF-α at transcription levels. Oxidative stress was investigated by colorimetric measurement of MDA, GSH and catalase. (3) Results: Contrary to the Cis group (p < 0.05), BM-MSCs/RA supplementation resulted in a substantial decrease in serum levels of hepatic impairment indicators such as ALT, AST and oxidative stress markers such as MDA, as well as an increase in hepatic GSH, Catalase, and a decrease in expression of TNF-α and downregulation of NADPH oxidase. The improvement after therapy with BM-MSCs/RA was confirmed by histopathological examination. Moreover, the downregulation of caspase-3 in liver tissue after BM-MSCs/RA treatment was validated by immunohistochemistry investigation. (4) Conclusions: BM-MSCs and RA attenuated Cis induced hepatotoxicity through downregulation of oxidative stress resulted in modulation of anti-inflammatory TNF-α and apoptosis caspase-3 indicating a promising role in hepatotoxicity.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-09-29
      DOI: 10.3390/scipharm90040058
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 59: Potential and Alternative Bioactive
           Compounds from Brown Agaricus bisporus Mushroom Extracts for Xerosis
           Treatment

    • Authors: Nichcha Nitthikan, Pimporn Leelapornpisid, Ornchuma Naksuriya, Nutjeera Intasai, Kanokwan Kiattisin
      First page: 59
      Abstract: This study aimed to investigate the ability of brown Agaricus bisporus extracts to enhance xerosis treatment via their biological activities, including their antioxidant, anti-aging, and anti-inflammation. Brown A. bisporus ethanol extract (EE) and brown A. bisporus water extract (WE) contained ergothioneine and gallic acid as their major compounds, as detected by HPLC, respectively. The WE exhibited the highest total polysaccharide content (734.04 ± 0.03 mg glucose/g extract) and total phenolic content (190.90 ± 0.07 mg gallic acid/g extract). The WE exhibited an inhibitory effect of 83.34 ± 18.66% on a collagenase enzyme, whereas the EE inhibited the elastase enzymes by 81.26 ± 4.37%. In addition, the EE also demonstrated strong activities against DPPH, with an IC50 0.30 ± 0.04 mg/mL, ABTS with a TEAC value of 8.06 ± 0.08 µM Trolox/g extract, and a FRAP assay with a FRAP value of 390.50 ± 0.32 mM FeSO4/g. In addition, all extracts were non-cytotoxic and could decrease the secretion of IL-6 and TNF-α in HaCaT cells. Therefore, brown A. bisporus extracts might be a potential natural raw material that can be further used in cosmeceutical products for xerosis treatment due to their good efficacy.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-05
      DOI: 10.3390/scipharm90040059
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 60: Green Synthesis of Silver Nanoparticles
           Using Bellevalia Flexuosa Leaves Extract

    • Authors: Nusaiba Al-Nemrawi, Fatima Hameedat, Tamam El-Elimat
      First page: 60
      Abstract: Silver nanoparticles (AgNPs) have broad biocidal activities, and are widely employed as an active ingredient in antiseptic, anti-viral, and anti-inflammatory preparations. Green-synthesizing AgNPs would be a rapid, cheap, and environmentally friendly method of synthesis. The methanolic extract of the leaves of Bellevalia flexuosa Boiss. (Asparagaceae) was used for the green synthesis of the AgNPs. The effects of the pH and the concentration of silver nitrate (AgNO3) on the synthesis of the AgNPs were investigated. The AgNPs produced above pH 10, and 1 mM of AgNO3 resulted in lower hydrodynamic diameters. Ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction proved the formation of the AgNPs, with a face-centered, cubed geometry. Scanning electron microscopy images showed colloidal and well-dispersed nanoparticles. In addition, the antibacterial activities of the prepared AgNPs were assessed by optical densities (ODs) against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus epidermidis) and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica). The broths of Gram-negative and Gram-positive bacteria that contained AgNPs, showed lower OD values compared to the controls. In conclusion, AgNPs were prepared using B. flexuosa methanolic extract, and showed antibacterial activity against the tested bacterial strains.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-06
      DOI: 10.3390/scipharm90040060
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 61: The Effect of Zinc Oxide Nanoparticles on
           Properties and Burn Wound Healing Activity of Thixotropic Xymedone Gels

    • Authors: Ilya Sheferov, Alyona Balakireva, Dmitry Panteleev, Irina Spitskaya, Sergey Orekhov, Oleg Kazantsev, Anna Solovyeva, Denis Novopoltsev, Nina Melnikova
      First page: 61
      Abstract: Zinc oxide nanoparticles (ZnO NPs) modified by oxopyrymidine alcohol, also known as xymedone (Xym), were obtained and studied using FTIR, UV-vis, and fluorescent spectroscopy, and SEM, BET, powder XRD, and DLS analysis. A formulation of thixotropic hydrophilic gels containing Carbopol-based Xym and ZnO NPs was developed. A vertical Franz cell with a cellulose acetate membrane was used as a model to investigate the passive diffusion of the gel components by AAS. The gel components—Xym and ZnO NPs—were shown to penetrate through acetyl cellulose membrane within 5–7 h depending on an initial amount, and its values were in the range of 56–77%. The penetration of modified ZnO NPs by Xym was more effective in contrast to ZnO NPs without modification. The burn wound healing activity of ZnO NPs–Xym gel was demonstrated on a thermal burn wound model on rats. SOD and GR activity was increased by 30–35% during ZnO NPs–Xym gel treatment, the burn area on 10 postburn day decreased by 10% in contrast to a positive control, Methyluracyl®® ointment.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-08
      DOI: 10.3390/scipharm90040061
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 62: Production of Bovine Collagen Hydrolysate
           with Antioxidant Activity; Optimized by Response Surface Methodology

    • Authors: Pakbin, Allahyari, Dibazar, Brück, Vahidi, Mahmoudi, Khanjari
      First page: 62
      Abstract: Antioxidants are widely used in pharmaceutical industries. Gelatin is a byproduct of the meat industry and its hydrolysates showed several functionalities, such as antioxidant activity. The purpose of this study was to describe and optimize the enzymatic hydrolysis conditions including time, temperature, pH, and enzyme/substrate ratio (E/S) to produce protein hydrolysate with antioxidant functionality from bovine gelatin by RSM; the scavenging activity was evaluated using the DPPH method. The model observed was fitted with desirable adequacy and sufficiency. We found that the antioxidant activity increased significantly (p < 0.05) with the increase in pH value, E/S ratio, and time of enzymatic process; however, the temperature had no significant (p < 0.05) effect on the antioxidant activity of the hydrolysate. The optimum hydrolysis conditions were observed at a temperature of 35.3 °C, pH of 8.0, and E/S ratio at 2.5 after 2 h hydrolysis by trypsin enzyme. The results showed that the hydrolysate under these conditions, optimized by RSM, could be more effective on antioxidant activity. Regarding the antioxidant potential, gelatin hydrolysate can be used as an antioxidant supplement in pharmaceutical industries.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-10
      DOI: 10.3390/scipharm90040062
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 63: Synthesis and Anticholinesterase
           Evaluation of Cassine, Spectaline and Analogues

    • Authors: Marcela C. R. Silva, Adriana F. L. Vilela, Carmen L. Cardoso, Ronaldo A. Pilli
      First page: 63
      Abstract: In this work, twelve analogues of piperidine alkaloids (-)-cassine and (-)-spectaline were synthesized, as well as the racemic forms of these natural products. The compounds were evaluated for their inhibition of electric eel acetylcholinesterase (AChEee) and human butyrylcholinesterase (BChEhu) by on-flow mass-spectrometry-based dual-enzyme assay, and the inhibition mechanisms for the most potent analogues were also determined. Our results showed a preference for BChEhu inhibition with compounds 10c (Ki = 5.24 μM), 12b (Ki = 17.4 μM), 13a (Ki = 13.2 μM) and 3 (Ki = 11.3 μM) displaying the best inhibitory activities.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-13
      DOI: 10.3390/scipharm90040063
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 64: GC-MS Analysis of the Phytochemical
           Constituents, Safety Assessment, Wound Healing and Anti-Inflammatory
           Activities of Cucurbita pepo Leaf Extract in Rats

    • Authors: Emmanuel Iroha Akubugwo, Okezie Emmanuel, Celestine Nwabu Ekweogu, Ositadinma Chinyere Ugbogu, Tochukwu Remigius Onuorah, Ozioma Glory Egeduzu, Eziuche Amadike Ugbogu
      First page: 64
      Abstract: In traditional medicine, Cucurbita pepo L. is used for the treatment of rheumatism, diabetes, inflammations, and wound injuries. This study was conducted to evaluate the phytochemical constituents, safety profile, wound healing, and anti-inflammatory activities of Cucurbita pepo leaf extract in rats. The phytochemical analysis of C. pepo extract was carried out using gas chromatography-mass spectrometry (GC-MS). In acute toxicity tests, the rats orally received a single dose of 5 g/kg extract of C. pepo. In a subacute toxicity study, the rats received 200, 400, and 800 mg/kg of the C. pepo extract via daily gavage for 14 days. Bioactive compounds 1-octen-3-ol, nonanal, trans-β-ionone, phytol, trans-farnesol, and squalene were identified. There were no toxic effects detected in any of the evaluated parameters, namely liver, kidney, haematological, lipid, and antioxidant enzymes. In wound healing, C. pepo extract showed greater % wound contraction and tensile strength, as well as reduced wound healing time (12 days) and epithelialization when compared to the control (normal saline) and povidone-iodine treated groups. Rats treated with C. pepo extract elicit anti-inflammatory activity. The findings of this study revealed that the C. pepo extract has wound healing and anti-inflammatory properties with a wide margin of safety.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-14
      DOI: 10.3390/scipharm90040064
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 65: Concepts for a New Rapid and Simple HPLC
           Method for Simultaneous Determination of Metoprolol and Meldonium in
           Pharmaceutical Dosage Forms

    • Authors: Marjan Piponski, Mariana Horyn, Kristina Grncaroska, Oleksandra Oleshchuk, Elena Petrovska, Stefan Angelevski, Tetyana Uglyar, Tetyana Kucher, Liliya Logoyda
      First page: 65
      Abstract: Simultaneous determination of the tandem of drugs, like meldonium and metoprolol, with enormous polarity differences between them, requires thorough research and careful selection of chromatographic conditions. The three different CN-cyano groups with link-based particle columns, LiChrospher CN, Waters Spherisorb CNRP, Zorbax CN SB stationary phases, were tested, in an isocratic elution system, with a running mobile phase containing various concepts of composition contents. They were first with buffering salts which included acetonitrile and ammonium phosphate in one group, and then without buffering salts but with diluted acids, composed of acetonitrile and diluted acids as the second group. We can conclude that the most optimal concepts, in terms of expressiveness and environmental friendliness, were concepts using of column Zorbax CN SB (4.6 mm i.d.× 250 mm, 5 μm) and mobile phase ACN—0.15% NH4H2PO4 (50:50 and 60:40, v/v). There are very poor available data about ideas and usable information about the development of methods for simultaneous determination of these two active substances with polarity differences between them. We suggest that our work offered detailed and successful solutions for the mentioned aim using less sophisticated equipment for quality control and a lab for routine manufacturing control.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-17
      DOI: 10.3390/scipharm90040065
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 66: Orally Administered Prosochit®-Based
           Nanoparticles of Insulin Ameliorates Alloxan-Induced Diabetes in Rats

    • Authors: Emmanuel O. Olorunsola, Koofreh G. Davies, Enomfon B. Essien, Mfonobong F. Alozie, Musiliu O. Adedokun, Fakhrul Ahsan
      First page: 66
      Abstract: This work was aimed to assess the antidiabetic effect of orally administered Prosochit®-based nanoparticles of insulin in an animal model. Five batches of insulin-loaded nanoparticles were prepared as dry water-in-oil-in-water emulsions using different emulsifiers (prosopis gum, Prosochit® 201, Prosochit® 101, Prosochit® 102, and chitosan) for the outer emulsion. Unloaded Prosochit® 101-based nanoparticles were also formulated. The morphology and size distribution of the nanoparticles were studied using a scanning electron microscope and Zetasizer. Forty alloxan-induced diabetic Wistar rats were divided into eight groups. The different groups were administered daily with different formulations (unloaded nanoparticles, the 5 loaded nanoparticles equivalent to 50 IU insulin per kg, purified water, and Actrapid) for 14 days. Blood glucose level was monitored and determined over 24 h. Fasting blood sugar was also taken on days 3, 5, 7, and 14. A graph of the percent blood glucose level relative to time 0 h was plotted against time. The particles showed a water-in-oil-in-water constitution. Both the drug-loaded and the unloaded Prosochit®-based nanoparticles were of nano dimension. There was a significant difference (p < 0.0001) in the antidiabetic effects of all insulin-loaded nanoparticles compared with the negative control. There was no significant difference across the insulin-loaded nanoparticles of prosopis gum, Prosochit® 201, Prosochit® 102, and chitosan while the insulin-loaded Prosochit® 101 nanoparticles showed the best activity, which is comparable to subcutaneous insulin, reducing blood glucose levels to 32.20 ± 3.79%. All the oral Prosochit®-based insulin nanoparticles are characterized by appreciable antidiabetic activity with the activity of Prosochit® 101-based nanoformulation being comparable to that of the subcutaneous insulin.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-17
      DOI: 10.3390/scipharm90040066
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 67: Modification of Taxifolin Properties by
           Spray Drying

    • Authors: Amir Taldaev, Roman P. Terekhov, Irina A. Selivanova, Denis I. Pankov, Maria N. Anurova, Irina Yu. Markovina, Zhaoqing Cong, Siqi Ma, Zhengqi Dong, Feifei Yang, Yonghong Liao
      First page: 67
      Abstract: Taxifolin is known as an active pharmaceutical ingredient (API) and food supplement due to its high antioxidant activity, multiple pharmacological effects, and good safety profile. Previously, taxifolin spheres (TS) were obtained from industrially produced API taxifolin in Russia (RT). In our work, we perform a pharmaceutical analysis of this new taxifolin material versus RT. TS is an amorphous material; however, it is stable without the polymer carrier, as confirmed by Fourier transform infrared spectroscopy. Both RT and TS demonstrate high safety profiles and are assigned to Class 1 of the Biopharmaceutical Classification System based on the results of experiments with MDCK cells. The water solubility of the new taxifolin form was 2.225 times higher compared with RT. Hausner ratios for RT and TS were 1.421 and 1.219, respectively, while Carr indices were 29.63% and 19.00%, respectively. Additionally, TS demonstrated sustained release from tablets compared with RT: the half-life values of tablets were 14.56 min and 20.63 min for RT and TS, respectively. Thus, TS may be a promising object for developing oral antiseptics in the form of orally dispersed tablets with sustained release patterns because of its anti-inflammatory, -protozoal, and -viral activities.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-24
      DOI: 10.3390/scipharm90040067
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 68: Fabrication of Hydroxypropyl
           Methylcellulose Orodispersible Film Loaded Mirtazapine Using a Syringe
           Extrusion 3D Printer

    • Authors: Tanpong Chaiwarit, Niphattha Aodsab, Pimonnart Promyos, Pattaraporn Panraksa, Suruk Udomsom, Pensak Jantrawut
      First page: 68
      Abstract: Depression is a mental illness causing a continuous negative feeling and loss of interest and affects physical and mental health. Mirtazapine (MTZ) is an effective medicine for treating depression, but patients lack compliance. However, transforming a pharmaceutical dosage form to an orodispersible film (ODF) could resolve this issue. This study aims to fabricate ODF-loading mirtazapine, using a syringe extrusion 3D printer, and compare its properties with the solvent-casting method. The ODFs were prepared by dissolving the mirtazapine in a hydroxypropyl methylcellulose E15 solution, and then fabricated by a 3D printer or casting. The 3D printing was accurate and precise in fabricating the ODFs. The SEM micrographs showed that the mirtazapine-printed ODF (3D-MTZ) was porous, with crystals of mirtazapine on the film’s surface. The 3D-MTZ exhibited better mechanical properties than the mirtazapine-casted ODF (C-MTZ), due to the 3D-printing process. The disintegration time of the 3D-MTZ in a simulated salivary fluid, pH 6.8 at 37 °C, was 24.38 s, which is faster than the C-MTZ (46.75 s). The in vitro dissolution study, in 0.1 N HCl at 37 °C, found the 3D-MTZ quickly released the drug by more than 80% in 5 min. This study manifested that 3D-printing technology can potentially be applied for the fabrication of ODF-containing mirtazapine.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-26
      DOI: 10.3390/scipharm90040068
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 69: Ethanolic Extract of Ocimum sanctum Linn.
           Inhibits Cell Migration of Human Lung Adenocarcinoma Cells (A549) by
           Downregulation of Integrin αvβ3, α5β1, and VEGF

    • Authors: Ulayatul Kustiati, Suleyman Ergün, Srikanth Karnati, Dwi Aris Agung Nugrahaningsih, Dwi Liliek Kusindarta, Hevi Wihadmadyatami
      First page: 69
      Abstract: Adenocarcinoma lung cancer is a type of non-small cell lung carcinoma (NSCLC), which accounts for 85% of lung cancer incidence globally. The therapies that are being applied, both conventional therapies and antibody-based treatments, are still found to have side effects. Several previous studies have demonstrated the ability of the ethanolic extract of Ocimum sanctum Linn. (EEOS) as an ethnomedicine with anti-tumor properties. The aim of this study was to determine the effect of Ocimum sanctum Linn. ethanolic extract in inhibiting the proliferation, angiogenesis, and migration of A549 cells (NSCLC). The adhesion as well as the migration assay was performed. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of αvβ3 integrins, α5β1 integrins, and VEGF. The cells were divided into the following treatment groups: control (non-treated/NT), positive control (AP3/inhibitor β3 80 µg/mL), cisplatin (9 µg/mL), and EEOS at concentrations of 50, 70, 100, and 200 µg/mL. The results showed that EEOS inhibits the adhesion ability and migration of A549 cells, with an optimal concentration of 200 µg/mL. ELISA testing showed that the group of A549 cells given EEOS 200 µg/mL presented a decrease in the optimal expression of integrin α5β1, integrin αvβ3, and VEGF.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-10-31
      DOI: 10.3390/scipharm90040069
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 70: Anti-Sporotrichotic Activity, Lambert-W
           Inhibition Kinetics and 3D Structural Characterization of Sporothrix
           schenckii Catalase as Target of Glucosinolates from Moringa oleifera

    • Authors: Erick Sierra-Campos, Mónica A. Valdez-Solana, Estela Ruiz-Baca, Erica K. Ventura-García, Claudia I. Avitia-Domínguez, Miguel Aguilera-Ortiz, Alfredo Téllez-Valencia
      First page: 70
      Abstract: Most human fungal infections exhibit significant defensive oxidative stress responses, which contribute to their pathogenicity. An important component of these reactions is the activation of catalase for detoxification. To discover new antifungal chemicals, the antifungal activity of methanol extracts of Moringa oleifera from two commercial products (Akuanandi and Mas Lait) was investigated. The methanolic extracts’ activity against Sporothrix schenckii was determined using an assay for minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC). The MIC concentrations varied between 0.5 μg/mL and 8 μg/mL. Akuanandi extract had the lowest MIC (0.5 μg/mL) and MLC (1 μg/mL) values. M. oleifera methanolic extracts were tested for catalase inhibition. The Ki values of the M. oleifera extract against S. schenckii catalase (SsCAT) was found to be 0.7 μg/mL for MOE-AK and 0.08 μg/mL for MOE-ML. Catalase’s 3D structure in SsCAT is unknown. The homology of SsCAT was modeled with an in silico study using a 3D structure from SWISS MODEL and validation the predicted 3D structure was carried out using PROCHECK and MolProbity. Docking simulations were used to analyze protein interactions using Pymol, PoseView, and PLIP. The results revealed that M. oleifera glucosinolates interacts with SsCAT. A molecular interaction analysis revealed two inhibitor compounds (glucosinalbin and glucomoringin) with high binding affinity to key allosteric-site residues. The binding energies revealed that glucosinalbin and glucomoringin bind with high affinity to SsCAT (docking energy values: −9.8 and −9.0 kcal/mol, respectively). The findings of this study suggest that glucosinolates derived from M. oleifera could be used instead of synthetic fungicides to control S. schenckii infections. We hope that the findings of this work will be valuable for developing and testing novel natural anti-sporothrix therapeutic agents in the future.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-11-04
      DOI: 10.3390/scipharm90040070
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 71: Enhancement of the Solubility and
           Dissolution Rate of Telmisartan by Surface Solid Dispersions Employing
           Superdisintegrants, Hydrophilic Polymers and Combined Carriers

    • Authors: Reem A. Aldeeb, Mohamed Farid El-Miligi, Mohamed El-Nabarawi, Randa Tag, Hany M. S. Amin, A. A. Taha
      First page: 71
      Abstract: Telmisartan (Tel) is a potent antihypertensive drug with a very poor aqueous solubility, especially in pH ranging from 3 to 9 (i.e., biological fluids) that results in poor bioavailability. Our aim was to improve Tel solubility and dissolution rates without the need for expensive multistep procedures, and without inclusion of alkalinizers. This study adopted the use of surface solid dispersions (SSDs) employing superdisintegrants, hydrophilic polymers and combined carriers including a superdisintegrant with a hydrophilic polymer. Tel-SSDs were formulated using thesolvent evaporation method. Compatibility between Tel and different carriers was examined via FT-IR. Tel-SSDs were evaluated optically and thermally to reveal a complete loss of the crystalline nature of the drug. Both drug content and percentage yield were calculated to judge the efficiency of the preparation technique used. Saturation, aqueous solubility, and dissolutions rates were determined. Dissolution profiles were studied using model dependent and independent approaches and were subjected to the pair-wise procedure using the DDsolver software program. Effect of aging was studied by comparing the drug content and dissolution profiles of freshly prepared SSDs with aged samples. All Tel-SSDs showed acceptable physical properties. Tel-SSDs showed pertinent enhancement related to the carrier used. Combined surface solid dispersions employing superdisintegrant croscarmellose sodium with either hydrophilic polymer PEG 4000 or Poloxamer 407 gave remarkable enhancement in solubility and dissolution rates of Tel where more than 90% of the drug was released within 20 min. The effect of aging results proved a non-significant difference in the drug content and dissolution profiles between fresh and aged samples. Formulation of Tel SSDs using combined carriers proved to be effective in enhancing the aqueous solubility and dissolution rates of Tel, as well as showing good stability upon aging.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-11-04
      DOI: 10.3390/scipharm90040071
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 72: Uptake of Cationic PAMAM-PLGA
           Nanoparticles by the Nasal Mucosa

    • Authors: Mohammed A. Albarki, Maureen D. Donovan
      First page: 72
      Abstract: Nanoparticles provide promising advantages in advanced delivery systems for enhanced drug delivery and targeting. The use of a biodegradable polymer such as PLGA (poly lactic-co-glycolic acid) promotes improved nanoparticle safety and, to some extent, provides the ability to modify nanoparticle surface properties. This study compared the effect of altering the surface charge on the translocation of PLGA nanoparticles across excised nasal mucosal tissues. Nanoparticles (average diameter of 60–100 nm) loaded with Nile Red (lipophilic fluorescent dye) were fabricated using a nanoprecipitation method. The effects of nanoparticle surface charge were investigated by comparing the transfer of untreated nanoparticles (negatively charged) and positively charged PLGA nanoparticles, which were modified using PAMAM dendrimer (polyamidoamine, 5th generation). All nanoparticles were able to be transferred in measurable quantities into both nasal respiratory and olfactory mucosae within 30 min. The total nanoparticle uptake was less than 5% of the nanoparticle mass exposed to the tissue surface. The cationic nanoparticles showed a significantly lower transfer into the mucosal tissues where the amount of nanoparticles transferred was 1.8–4-fold lower compared to the untreated negatively charged nanoparticles. The modification of the nanoparticle surface charge can alter the nanoparticle interaction with the nasal epithelial surface, which can result in decreasing the nanoparticle transfer into the nasal mucosa.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-11-25
      DOI: 10.3390/scipharm90040072
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 73: Effect of Aqueous Extracts of Quercus
           resinosa on the Mechanical Behavior of Bigels

    • Authors: José Alberto Gallegos-Infante, María del Pilar Galindo-Galindo, Martha Rocío Moreno-Jiménez, Nuria Elizabeth Rocha-Guzmán, Rubén Francisco González-Laredo
      First page: 73
      Abstract: Quercus resinosa leaves are rich in polyphenol compounds, however, they are unstable to several chemical and physical factors that limit their activity. Several methods have been developed to solve such problems, among which bigels can be mentioned and obtained using hydrogels and oleogels. The mechanical characterization of this type of materials is by using rheological methods. Although the use of these methods is well documented, the Carreau-Yasuda model has been little used to evaluate the effect of polyphenols on the mechanical behavior of bigels. Therefore, bigels were obtained from hydrogels (guar gum/xanthan gum, 0.5/0.5% w/v) and oleogels (sesame oil/sorbitan monostearate 10% w/w). Micrographs, linear viscoelasticity range, frequency sweep, and single shear tests were performed. The data were analyzed using ANOVA and Tukey test (p < 0.05); micrographs showed linear relationship between polyphenols concentration and droplet size. Liquid fraction of bigels showed a pseudoplastic behavior, while the parameters of Carreau-Yasuda model showed that the highest value of the complex viscosity at zero shear was at the lowest concentration of extract; the relaxation time presented the lowest value at higher concentrations of extracts. These results indicate that the presence of polyphenols modifyes the mechanical behavior of bigels.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-11-28
      DOI: 10.3390/scipharm90040073
      Issue No: Vol. 90, No. 4 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 39: A Narrative Review of the Potential Roles
           of Lipid-Based Vesicles (Vesiculosomes) in Burn Management

    • Authors: Bazigha K. Abdul Rasool, Nema Al Mahri, Nora Alburaimi, Fatima Abdallah, Anfal Saeed Bin Shamma
      First page: 39
      Abstract: Burn injuries can have a lasting effect on people’s quality of life, as they negatively impact their physical and mental health. Then, they are likely to suffer psychological problems as a result. A serious problem is that deep burns are more challenging to treat due to their slow healing rate and susceptibility to microbial infection. Conventional topical medications used for burn treatment are sometimes ineffective because they cannot optimize their ability of transcutaneous absorption at the targeted site and accelerate healing. However, nanotechnology offers excellent prospects for developing current medical wound therapies and is capable of addressing issues such as low drug stability, water solubility, permeability, and bioavailability. The current review focuses on lipid-based vesicles (vesiculosomes) as an example of advanced delivery systems, showing their potential clinical applications in burn wound management. Vesiculosomes may help overcome impediments including the low bioavailability of active agents, offering the controlled release of drugs, increased drug stability, fewer side effects, and reduced dosing frequency, which will ultimately improve therapeutic efficacy and patient compliance. We discuss the application of various types of vesiculosomes such as liposomes, niosomes, ethosomes, cubosomes, transfersomes, and phytosomes in burn healing therapy, as these demonstrate superior skin penetration compared to conventional burn topical treatment. We also highlight their noteworthy uses in the formulation of natural products and discuss the current status as well as future perspectives of these carriers in burn management. Furthermore, the burn treatment options currently available in the market are also summarized.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-06-29
      DOI: 10.3390/scipharm90030039
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 40: Colorectal Cancer Chemoprevention by
           S-Allyl Cysteine–Caffeic Acid Hybrids: In Vitro Biological Activity
           and In Silico Studies

    • Authors: Angie Herrera-Ramirez, Andres F. Yepes-Pérez, Jorge Quintero-Saumeth, Gustavo Moreno-Quintero, Tonny W. Naranjo, Wilson Cardona-Galeano
      First page: 40
      Abstract: Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed at late stages, when the tumor has disseminated to other organs. Moreover, it is common to observe that malignant cells may acquire resistance to conventional chemotherapies through different mechanisms, including reducing drug activation or accumulation (by enhancing efflux), inducing alterations in molecular targets, and inhibiting the DNA damage response, among other strategies. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) that exhibited selective cytotoxicity against SW480 cells, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated the possible mechanisms of these molecules in greater depth, to identify whether they could be valuable therapeutic scaffolds in the search for new molecules with chemopreventive potential for the treatment of CRC. Both compounds reduced ROS formation, which could be related to antioxidant effects. Further evaluations showed that SAC-CAFA-MET induces cell death independent of caspases and the tumor-suppressor protein p53, but probably mediated by the negative regulation of the pro-apoptotic Bcl-2. In addition, the lack of activation of caspase-8 and the positive regulation of caspase-3 induced by SAC-CAFA-PENT suggest that this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathways. Furthermore, the downregulation of IL-6 by SAC-CAFA-PENT suggests that it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which SAC-CAFA-PENT elicits apoptosis in SW480human colorectal adenocarcinoma cells. Meanwhile, density functional theory (DFT) calculations suggest that both hybrids would produce effects in the modulation of ROS in SW480 cells via the hydrogen atom transfer (HAT) pathway. The present work notes that SAC-CAFA-MET and SAC-CAFA-PENT could be potential candidates for further investigations in the search for potential chemopreventive agents.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-06-30
      DOI: 10.3390/scipharm90030040
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 41: Emerging Approach for the Application of
           Hibiscus sabdariffa Extract Ointment in the Superficial Burn Care

    • Authors: Rania Khalil, Galal Yahya, Walied S. Abdo, Ghada S. El-Tanbouly, Dina Johar, Mahmoud Saad Abdel-Halim, Hanan Eissa, Calin Magheru, Sameh Saber, Simona Cavalu
      First page: 41
      Abstract: Wound healing comprises organized events involving tissue repair and regeneration. The discovery of toll-like receptors (TLRs) sheds recent light on the mechanisms involved in initiating inflammatory responses throughout the healing cascades. Hibiscus sabdariffa (HS) components may exhibit a wound healing action, owing to their antioxidant and anti-inflammatory activities. This study was designed to investigate the early effects of HS loaded in an ointment base on wound healing, antioxidant, antimicrobial effects, burning intensity, and histopathological features on the rat burn model in comparison to the standard treatment, Iruxol® ointment. A burn injury model was used to evaluate the wound healing potency of the preparation. Rats were treated with ointments three times on the day of the induction of the burn. Findings revealed that the strong antioxidant properties of the HS-loaded ointment augmented the skin healing potential by stimulating biomarkers required for skin regeneration. HS repressed the burning-induced inflammation by the effective reduction in the levels of tumor necrosis factor α (TNF-α) and IL-6 through TLR4 protein inhibition. Topical HS downregulates transforming growth factor-beta (TGF-β) levels. HS extract possesses a potential bactericidal activity against highly resistant clinical isolates of Pseudomonas aeruginosa. Overall, this study proclaims that HS-loaded topical preparations could be a valuable product that serves as adjuvants to accelerate burn wound healing through inactivating the TLR4 pathway.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-06-30
      DOI: 10.3390/scipharm90030041
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 42: Sitagliptin Potentiates the
           Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary
           Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation,
           Angiogenesis, and Apoptosis

    • Authors: Mohamed M. Salama, Randa A. Zaghloul, Rania M. Khalil, Mamdouh M. El-Shishtawy
      First page: 42
      Abstract: Sitagliptin (STG) is a highly selective dipeptidyl peptidase-4 inhibitor recently used in the treatment of type 2 diabetes. The current study aimed to investigate the anti-neoplastic effect of STG alone and in combination with Doxorubicin (Dox), a known chemotherapeutic agent but with ominous side effects. After intramuscular inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice were divided into tumor-bearing control, STG-treated, Dox-treated, and a combination of STG and Dox-treated groups. The results showed a significant reduction in the tumor growth of the treated animals in comparison with those of the positive control group with a more prominent effect in the co-treated group. Where, the anti-proliferative and apoptotic effect of STG, and its chemo-sensitizing ability, when used in combination with Dox, was mediated by modulation of oxidative stress (MDA and GSH), attenuation of tumor inflammation (IL-6 and IL-1β), and angiogenesis (VEGF), suppressing proliferation (β-catenin and cyclin-D1) and enhancement of apoptosis (survivin, p53, caspase 3). Thus, in conclusion, STG as adjunctive therapy for Dox could be a strategy for the treatment of breast cancer patients, by their ability in hindering cell proliferation and minimizing the associated oxidative and inflammatory adverse reactions.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-07-07
      DOI: 10.3390/scipharm90030042
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 43: Bimodal Release Two-In-One Clonazepam
           Matrix Lozenge Tablets for Managing Anxiety-Related Disorders:
           Formulation, Optimization and In Vivo Evaluation

    • Authors: Eman Gomaa, Sami El Deeb, Adel Ehab Ibrahim, Mennatullah M. Faisal
      First page: 43
      Abstract: Clonazepam (CLZ), an antipsychotic drug reported for its efficiency in managing anxiety-related disorders, is being marketed only as conventional tablets. Some patients have abstention to swallow the conventional tablets; therefore, the proposed study was aimed at developing a buccal lozenge tablet by direct compression of two types of optimized granules. Conazepam’s water solubility was first enhanced by a solid dispersion technique for a fast and better dissolution of type 1 granules, while the impact of gelling polymers was investigated on controlled-release type 2 granules. The optimized formulae met the acceptable pharmacopeial limits for tablets’ evaluation. A differential scanning calorimetry study revealed the compatibility between the drug and used excipients. All formulae gave a burst release of CLZ in the first hour of investigation, followed by a sustained release over 24 h. The formula that showed the highest prolonged in vitro release (99.0 + 0.1%), following the Higuchi diffusion model (R2 = 0.99), was then selected for further study. The formula succeeded in controlling the induced stress in a rat model with a significant impact on the behavioral tests throughout the experiment. The results were further confirmed by a pharmacokinetic study that showed a significant increase in Cmax, Tmax, and AUC (1.5, 2, and 3.9 folds), respectively, compared to oral suspension. The newly proposed delivery system has proven a better efficacy with a reduced dosing frequency.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-07-21
      DOI: 10.3390/scipharm90030043
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 44: Ruellia tuberosa Ethyl Acetate Leaf
           Extract Induces Apoptosis and Cell Cycle Arrest in Human Breast Cancer
           Cell Line, MCF-7

    • Authors: Fui Fui Lem, Bo Eng Cheong, Peik Lin Teoh
      First page: 44
      Abstract: Ruellia tuberosa L. has been previously shown to possess antioxidant and antiproliferative activities on cancer cells but its underlying mechanisms are largely unknown. This study aimed to elucidate the mode of action underlying this inhibitory effect on MCF-7 using ethyl acetate extract obtained after liquid-liquid partition of methanol crude extract. Antiproliferative effect of R. tuberosa ethyl acetate leaf extract (RTEAL) was evaluated using MTT assay. Its ability to induce apoptosis was assessed by DNA ladder formation, JC-1, Annexin V, and methylene blue staining assays. Perturbation of cell cycle progression was determined using flow cytometry. RTEAL was found to selectively inhibit the proliferation of MCF-7 cells with the IC50 value of 28 µg/mL. Morphological changes such as nuclear fragmentation and chromatin condensation were observed although DNA laddering was undetected in agarose gel. RTEAL-induced apoptotic pathways by inhibiting the expression of anti-apoptotic BCL-2 while upregulating pro-apoptotic BAX, caspase 7 and caspase 8. RTEAL also caused cell cycle arrests at the S and G2/M phase and dysregulation of cell cycle regulators. These findings collectively demonstrate that RTEAL extract inhibited cell growth by inducing apoptosis and cell cycle arrest, suggesting its therapeutic potential against breast cancer.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-07-25
      DOI: 10.3390/scipharm90030044
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 45: Apoptosis Induction Associated with
           Enhanced ER Stress Response and Up-Regulation of c-Jun/p38 MAPK Proteins
           in Human Cervical Cancer Cells by Colocasia esculenta var. aquatilis Hassk
           Extract

    • Authors: Natharika Chomlamay, Watcharaporn Poorahong, Sukanda Innajak, Ramida Watanapokasin
      First page: 45
      Abstract: Colocasia esculenta var. Aquatilis Hassk, elephant ear (CF-EE) has been widely used as traditional food and medicine. It also shows other therapeutic properties, such as antimicrobial and anti-cancer activity. In this study, we aim to investigate the effect of CF-EE extract on apoptosis induction associated with ER stress in cervical cancer HeLa cells. Cell viability was determined by MTT assay. Assessments of nuclear morphological changes, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) production were conducted by hoeshst33342, JC-1, and DCFH-DA fluorescence staining, respectively. Sub-G1 DNA content was analyzed by flow cytometry, and protein expression was determined by Western blotting. The results demonstrate that CF-EE extract suppressed HeLa cell growth and induced nuclear condensation and apoptotic bodies. There was also a loss of mitochondrial membrane potential and increased apoptosis marker protein expression, including Bax, cleaved-caspase-7, and cleaved-PARP. In addition, the results show that CF-EE extract induced ROS, increased ER stress proteins (GRP78 and CHOP), enhanced p38 and c-Jun phosphorylation, and inhibited Akt expression in HeLa cells. In summary, CF-EE extract induced apoptotic cell death-associated ROS-induced ER stress and the MAPK/AKT signaling pathway. Therefore, CF-EE extract has anticancer therapeutic potential for cervical cancer treatment in the future.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-07-25
      DOI: 10.3390/scipharm90030045
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 46: Synthesis and Evaluation of
           (1,4-Disubstituted)-1,2,3-triazoles as Estrogen Receptor Beta Agonists

    • Authors: Edward A. Wetzel, Grace C. Corriero, Sandra Brown-Ford, Daniel S. Sem, William A. Donaldson
      First page: 46
      Abstract: Estrogen receptors (ER) are nuclear hormone receptors which are responsible for sex hormone signaling in women. A series of (1,4-disubstituted)-1,2,3-triazoles 5–21 were prepared by reaction of azidophenols with terminal alkynes under Fokin reaction conditions. The products were purified by column chromatography or recrystallization and characterized by NMR and HRMS. The compounds were tested for binding to ERβ via a ligand displacement assay, and 1-(4-hydroxyphenyl)-α-phenyl-1,2,3-triazole-4-ethanol (21) was found to be the most potent analog (EC50 = 1.59 μM). Molecular docking of 5–21 within the ligand binding pocket of ERβ (pdb 2jj3) was performed and the docking scores exhibited a general qualitative trend consistent with the measured EC50 values.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-08-01
      DOI: 10.3390/scipharm90030046
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 47: 2D-QSAR and CoMFA Models for
           Antitubercular Activity of Scalarane-Type Sesterterpenes

    • Authors: Suriyan Thengyai, Yuewei Guo, Khanit Suwanborirux, Heinz Berner, Helmut Spreitzer, Peter Wolschann, Supa Hannongbua, Anuchit Plubrukarn
      First page: 47
      Abstract: A series of scalarane sesterterpenes were prepared using heteronemin (1) as a primary precursor. Combined with the scalarane derivatives obtained from natural sources, a total of 22 antitubercular scalaranes were used to build QSAR models based in the 2D-QSAR and CoMFA approaches. Both models indicated the influences of substitutions in the vicinity of C-12 and C-16 of the scalaranes. A 2D-QSAR model suggested the necessity of hydrophilic functionalities on the peripherals with hydrophobic cores, and the lowering steric repulsion to improve the potential energy. This was complemented by the pictorial CoMFA model, which indicated the importance of the positive electrostatic with shortened steric extension crowning over C-12 and the lengthy negative functionalities extended from C-16.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-08-15
      DOI: 10.3390/scipharm90030047
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 48: Uncovering Streptomyces-Derived Compounds
           as Cosmeceuticals for the Development of Improved Skin Photoprotection
           Products: An In Silico Approach to Explore Multi-Targeted Agents

    • Authors: Jeysson Sánchez-Suárez, Luisa Villamil, Luis Díaz, Ericsson Coy-Barrera
      First page: 48
      Abstract: The search for novel photoprotective substances has become a challenge in cosmeceutical research. Streptomyces-derived compounds can serve as a promising source of photoprotective agents to formulate skin photoprotection products, such as sunscreens. This study aimed to identify specialized metabolites with the potential to modulate UV-induced cellular damage in the skin by identifying potential multi-target-directed ligands. Using a combination of ligand- and target-based virtual screening approaches, a public compound library comprising 6524 Streptomyces-derived specialized metabolites was studied for their photoprotective capability. The compounds were initially filtered by safety features and then examined for their ability to interact with key targets in the photodamage pathway by molecular docking. A set of 50 commercially available UV filters was used as the benchmark. The protein–ligand stability of selected Streptomyces-derived compounds was also studied by molecular dynamics (MD) simulations. From the compound library, 1981 compounds were found to meet the safety criteria for topically applied products, such as low skin permeability and low or non-toxicity-alerting substructures. A total of 34 compounds had promising binding scores against crucial targets involved in UV-induced photodamage, such as serotonin-receptor subtype 5-HT2A, platelet-activating factor receptor, IL-1 receptor type 1, epidermal growth factor receptor, and cyclooxygenase-2. Among these compounds, aspergilazine A and phaeochromycin F showed the highest ranked interactions with four of the five targets and triggered complex stabilization over time. Additionally, the predicted UV-absorbing profiles also suggest a UV-filtering effect. Streptomyces is an encouraging biological source of compounds for developing topical products. After in silico protein–ligand interactions, binding mode and stabilization of aspergilazine A and phaeochromycin F led to the discovery of potential candidates as photodamage multi-target inhibitors. Therefore, they can be further explored for the formulation of skin photoprotection products.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-08-16
      DOI: 10.3390/scipharm90030048
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 49: Effects of Origanum vulgare and
           Scutellaria baicalensis on the Physiological Activity and Biochemical
           Parameters of the Blood in Rats on a High-Fat Diet

    • Authors: Maryna Lieshchova, Viktor Brygadyrenko
      First page: 49
      Abstract: The pharmacological effects of medicinal plants play a primary role in the mild correction of body weight in humans and animals, reducing the accumulation of fat in their bodies during a state of obesity. Origanum vulgare L. and Scutellaria baicalensis Georgi are widely used as food additives and medicinal plants, but their comprehensive physiological evaluation in model animals in a state of obesity has not been carried out. In a 30-day laboratory experiment on male rats which had developed obesity through a hypercaloric diet, the effects of adding the dry crushed grass O. vulgare or dry crushed roots of S. baicalensis to their feed was evaluated. During the experiment, the rats fed with O. vulgare increased in body weight to only 105.5% of their initial weight, while the body weight of the control group increased to 111.5%, and that of animals fed on S. baicalensis increased to 124.0% of their initial body weight. The average daily increase in the rats’ body weight when O. vulgare was added to their diet decreased to 205 mg/day, and when S. baicalensis was added, on the contrary, it increased to 1417 mg/day, compared to 700 mg/day among the control group. Under the influence of O. vulgare, the lipid metabolism of the rats normalized: the atherogenic index decreased to 33.7%, compared with the values of the control group, due to an increase in the concentration of high-density lipoproteins from cholesterol. The concentration of triglycerides decreased, and the concentration of glucose decreased. The roots of S. baicalensis being added into the diet of rats increased the activity of alkaline phosphatase and decreased the concentration of urea. The atherogenic index also decreased (by up to 35.5% in the control group) and the concentration of high-density lipoprotein cholesterol increased, while the concentrations of triglycerides and glucose decreased. The physical activity of the rats showed a slight tendency to decrease when both O. vulgare and S. baicalensis were added to their diet. Both plant species contributed to a decrease in the emotional status of animals, which was most pronounced when the O. vulgare grass was added to the feed. The results of the study demonstrate the potential of the use of O. vulgare and S. baicalensis as herbal supplementations for the correction of hyperlipidemia and type-2 diabetes mellitus in overweight patients.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-08-18
      DOI: 10.3390/scipharm90030049
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 50: Antidepressant Effect of Neuropeptide Y in
           Models of Acute and Chronic Stress

    • Authors: Nika Andriushchenko, Kira Nebogina, Yana Zorkina, Olga Abramova, Eugene Zubkov, Aleksandra Ochneva, Valeria Ushakova, Konstantin Pavlov, Olga Gurina, Vladimir Chekhonin, Anna Morozova
      First page: 50
      Abstract: The search for potential effective antidepressants with minimal side effects is necessary. Peptides are possible applicants for this role. We investigated the antidepressant effect of neuropeptide Y (NY), alone and in combination with clomipramine, in models of acute and chronic stress induced by ultrasound of variable frequencies. Rats were divided into the following groups: the control group, stress group, and stress groups with intranasal administration of NY (100 μg/kg) or clomipramine (7.5 mg/kg), or their combination. Rat behavior was evaluated using a sucrose preference test and forced swimming test in an acute stress model, and a sucrose preference test, forced swimming test, social interaction test, open field test, and Morris water maze test in a chronic stress model. The results of our experiment demonstrated a protective effect of intranasal NY in a model of acute stress, which was comparable to the antidepressant effect of clomipramine. When the same dose was chronically administered, NY also demonstrated an antidepressant action, although expressed in a lesser degree than clomipramine. The combination of NY and clomipramine was much less effective in the chronic stress paradigm compared to the separated drug administration, but was just as effective in the acute stress paradigm. Until now, there was no convincing evidence for the efficacy of the chronic administration of neuropeptide Y; we demonstrated its effectiveness in the animal model of depressive-like behavior. However, our hypothesis that neuropeptide Y can enhance the effect of a classical antidepressant was not confirmed.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-08-23
      DOI: 10.3390/scipharm90030050
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 51: Melt Fusion Techniques for Solubility
           Enhancement: A Comparison of Hot Melt Extrusion and KinetiSol®
           Technologies

    • Authors: Srinivas Ajjarapu, Srikanth Banda, Pratap Basim, Narendar Dudhipala
      First page: 51
      Abstract: A successful candidate for oral drug delivery needs to possess adequate solubility and dissolution rate to elicit its therapeutic action. Extensive research is being carried out to enhance the solubility of poorly soluble drugs through a number of techniques involving polymeric and non-polymeric approaches. Non-polymeric approaches such as micronization and nanocrystals are successful in improving the apparent solubility of drugs, but the sustenance of solubility is not always possible. Amorphous solid dispersions (ASDs) lead to solubility enhancement as well as the maintenance of solubility with the assistance of polymers, thereby improving bioavailability. Spray drying, hot melt extrusion (HME), and KinetiSol® technologies are some of the techniques capable of manufacturing ASDs. Each of these techniques has its own advantages and disadvantages in terms of processing challenges and applicability in preparing ASDs. The latter two technologies are similar in being fusion and non-solvent techniques to improve solubility. This review compares both HME and KinetiSol® techniques regarding mechanism, equipment design, formulation, and process parameters involved and scalability.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-08-24
      DOI: 10.3390/scipharm90030051
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 52: New Quinazolin-4(3H)-one Derivatives
           Incorporating Hydrazone and Pyrazole Scaffolds as Antimicrobial Agents
           Targeting DNA Gyraze Enzyme

    • Authors: Eman M. Mohi El-Deen, Eman S. Nossier, Eman A. Karam
      First page: 52
      Abstract: The present work includes the synthesis of a new series of quinazolin-4(3H)-one compounds (4a–f, 5a–d) as antimicrobial agents. The starting compound, 2-hydrazinylquinazolin-4(3H)-one (2), was synthesized and treated with different carbonyl compounds to afford the hydrazone derivatives 4a–f. In addition, the hydrazone derivatives 4a–d were treated with a DMF/POCl3 mixture to give the formyl-pyrazole derivatives 5a–d. All the target compounds were evaluated as antimicrobial agents against four bacterial and four fungal strains. The majority of the tested compounds showed potent antimicrobial activity compared with the reference antibiotics. The most potent antimicrobial activity was shown by 5a with MIC values in the range (1–16) μg/mL. In addition, the most potent compounds against E. coli were evaluated for their inhibitory activity against E. coli DNA gyrase, whereas the target compounds 4a, 5a, 5c, and 5d showed the most potent inhibition to the target enzyme with IC50 values ranging from 3.19 to 4.17 µM. Furthermore, molecular docking studies were performed for the most active compounds against the target E. coli DNA gyrase to determine their binding affinity within the enzyme’s active site. Moreover, ADME evaluations of these compounds predicted their high oral bioavailability and good GI absorption.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-08-26
      DOI: 10.3390/scipharm90030052
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 53: Development of HPLC Method for
           Simultaneous Determination of Ibuprofen and Chlorpheniramine Maleate

    • Authors: Hasan Aldewachi, Thamer A. Omar
      First page: 53
      Abstract: One of the most prevalent over-the-counter cold and cough medications is the chlorpheniramine maleate (CPM)–ibuprofen (IBF) combination. A reversed-phase high-performance liquid chromatography (RP-HPLC) method was effectively optimized and developed for the simultaneous detection of chlorpheniramine maleate and ibuprofen in a pharmaceutical formulation. The mobile phase for the RP-HPLC method was an isocratic combination of acetonitrile and 0.01 M acetate buffer at pH 3.8 (55:45; v/v) on an Eclipse Plus C18 reversed phase column. An ultraviolet (UV) detector with a wavelength of 225 nm was used to detect the analytes at a flow rate of 1.0 mL/min. CPM and IBF were satisfactorily eluted, with mean retention times of 2.09 and 6.27 min, respectively. The approach was shown to be linear (R2 > 0.9998 for CPM and 0.9992 for IBF), precise (% RSD 3.02% for CPM and 3.48% for IBF), accurate (% recoveries 97.7–98.9% for CPM and 101–104.5% for IBF), specific, easy to use, sensitive, quick, and robust. Limits of detection (LODs) were found to be 10 and 27 μg/mL for CPM and IBF, respectively. Without interference from excipients, the validated method could be utilized in regular quality control analysis of various dosage combinations of hard gelatin capsules containing CPM and IBF.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-08-30
      DOI: 10.3390/scipharm90030053
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 54: Molecularly-Imprinted SERS: A Potential
           Method for Bioanalysis

    • Authors: Hilda Aprilia Wisnuwardhani, Slamet Ibrahim, Rino R. Mukti, Sophi Damayanti
      First page: 54
      Abstract: The most challenging step in developing bioanalytical methods is finding the best sample preparation method. The matrix interference effect of biological sample become a reason of that. Molecularly imprinted SERS become a potential analytical method to be developed to answer this challenge. In this article, we review recent progress in MIP SERS application particularly in bioanalysis. Begin with the explanation about molecular imprinting technique and component, SERS principle, the combination of MIP SERS, and follow by various application of MIP SERS for analysis. Finally, the conclusion and future perspective were also discussed.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-09-07
      DOI: 10.3390/scipharm90030054
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 55: LC-HRMS-Based Profiling: Antibacterial and
           Lipase Inhibitory Activities of Some Medicinal Plants for the Remedy of
           Obesity

    • Authors: Basanta Kumar Sapkota, Karan Khadayat, Babita Aryal, Jyoti Bashyal, Shankar Jaisi, Niranjan Parajuli
      First page: 55
      Abstract: Globally, obesity is a serious health concern that causes numerous diseases, including type 2 diabetes, hypertension, cardiovascular diseases, etc. Medicinal plants have been used to aid in weight loss since ancient times. Thus, this research is focused on the exploration of pancreatic lipase inhibitory activity and secondary metabolite profiling of Bergenia ciliata, Mimosa pudica, and Phyllanthus emblica, selected based on an ethnobotanical survey. The lipase inhibition was investigated using 4-nitrophenyl butyrate (p-NPB) as a substrate. To uncover further therapeutic potentials of these medicinal plants, antimicrobial activity and minimum inhibitory concentration (MIC) of the extracts were also determined. The ethyl acetate plant extracts showed higher antimicrobial activity against Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Shigella sonnei. The MIC of ethyl acetate extracts of medicinal plants considered in this study ranges from 1.56 to 6.25 mg/mL. The hexane fraction of Mimosa pudica and Phyllanthus emblica showed a higher lipase inhibitory activity as compared to others, with IC50 values of 0.49 ± 0.02 and 2.45 ± 0.003 mg/mL, respectively. In the case of Bergenia ciliata, the methanolic extract inhibited lipase more effectively than others, with an IC50 value of 1.55 ± 0.02 mg/mL (IC50 value of orlistat was 179.70 ± 3.60 µg/mL). A mass spectrometry analysis of various solvent/solvent partition fractions (extracts) revealed 29 major secondary metabolites. The research offers a multitude of evidence for using medicinal plants as antiobesity and antimicrobial agents.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-09-08
      DOI: 10.3390/scipharm90030055
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 56: Evaluation of
           5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone
           (Les-6222) as Potential Anticonvulsant Agent

    • Authors: Mariia Mishchenko, Sergiy Shtrygol’, Andrii Lozynskyi, Mykhailo Hoidyk, Dmytro Khyluk, Tatyana Gorbach, Roman Lesyk
      First page: 56
      Abstract: It was determined that the studied 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone (Les-6222) affects the cyclooxygenase pathway of the arachidonic acid cascade, the markers of damage to neurons on models of PTZ kindling. In the model of chronic epileptogenesis in mice (pentylenetetrazole kindling), a 4-thiazolidinone derivative showed high anticonvulsant activity, which is weaker than the effect of sodium valproate and higher than Celecoxib. The mentioned compound has a pronounced anti-inflammatory effect in the brain on the background of the PTZ kindling, reliably inhibiting COX-1 and COX-2. The predominant inhibition of COX-2 by 44.5% indicates this enzyme’s high selectivity of Les-6222. According to the molecular docking study results, the studied compound revealed the properties of COX-1/COX-2 inhibitor and especially 5-LOX/FLAP. The decreasing content of 8-isoprostane in the brain of mice of the Les-6222 group indicates a beneficial effect on cell membranes in the background of oxidative stress during the long-term administration of PTZ. In addition, Les-6222 significantly decreased the content of neuron-specific enolase, indicating neuroprotective properties in the background of chronic epileptogenesis. The obtained results experimentally substantiate the feasibility of further developing Les-6222 as a promising anticonvulsant agent.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-09-19
      DOI: 10.3390/scipharm90030056
      Issue No: Vol. 90, No. 3 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 22: Cinnamaldehyde Relieves Induced
           Hepatocellular Carcinoma in Rat Model via Targeting Wnt/β-Catenin
           Pathway

    • Authors: Al Shaima G. Abd El Salam, Yara A. Samra, Mamdouh M. El-Shishtawy
      First page: 22
      Abstract: Cinnamaldehyde (CA) is a natural compound that has promising biological activity. The current study investigates the antitumor activity of CA in thioacetamide induced hepatocellular carcinoma (HCC) in rats through targeting the Wnt/β-catenin pathway and evaluates the capability of CA to relieve hepatocytes oxidative stress in the HCC-rat model. After 16 weeks of HCC induction by thioacetamide (TAA), rats were treated for 7 consecutive weeks with CA daily; i.p. injection, Alpha-fetoprotein (AFP) level, necroinflammatory score and fibrosis percentage were measured to assess HCC development. The Wnt/β-catenin pathway was evaluated by measuring the hepatic protein level of Wnt-3a, β-catenin, cyclin D, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF). Furthermore, hepatocytes’ oxidative stress was assessed by measuring hepatic GSH and MDA contents. Results showed that CA was significantly inhibiting the Wnt/β-catenin pathway through the downregulation of hepatic Wnt-3a, β-catenin, cyclin D, MMP-9, and VEGF. Moreover, CA ameliorates hepatocytes’ oxidative stress via lowering hepatic MDA content and rising hepatic GSH content. Thus, in conclusion, CA is a promising treatment for HCC. It not only has an effective antitumor activity but also ameliorates hepatocytes’ oxidative stress.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-03-31
      DOI: 10.3390/scipharm90020022
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 23: Enhanced Antibacterial Activity of
           Brevibacillus sp. SPR19 by Atmospheric and Room Temperature Plasma
           Mutagenesis (ARTP)

    • Authors: Nuttapon Songnaka, Mudtorlep Nisoa, Apichart Atipairin, Thamonwan Wanganuttara, Thapanee Chinnawong
      First page: 23
      Abstract: Antibiotic resistance is a major health concern worldwide. In our previous study, some bacterial isolates exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). However, the production of antibacterial substances by native microorganisms is limited by biosynthetic genes. This study aimed to improve the antibacterial activity of SPR19 using atmospheric and room temperature plasma mutagenesis (ARTP). The results showed that SPR19 belonged to the Brevibacillus genus. The growth curves and production kinetics of antibacterial substances were investigated. Argon-based ARTP was applied to SPR19, and the 469 mutants were preliminarily screened using agar overlay method. The remaining 25 mutants were confirmed by agar well diffusion assay against S. aureus TISTR 517 and MRSA isolates 142, 1096, and 2468. M285 exhibited the highest activity compared to the wild-type strain (10.34–13.59%) and this mutant was stable to produce the active substances throughout 15 generations consistently. The antibacterial substances from M285 were tolerant to various conditions (heat, enzyme, surfactant, and pH) while retaining more than 90% of their activities. Therefore, Brevibacillus sp. SPR19 is a potential source of antibacterial substances. ARTP mutagenesis is a powerful method for strain improvement that can be utilized to treat MRSA infection in the future.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-04-06
      DOI: 10.3390/scipharm90020023
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 24: Repurposing of Four Drugs as
           Anti-SARS-CoV-2 Agents and Their Interactions with Protein Targets

    • Authors: Luis C. Vesga, Camilo A. Ruiz-Hernández, Jeimmy J. Alvarez-Jacome, Jonny E. Duque, Bladimiro Rincon-Orozco, Stelia C. Mendez-Sanchez
      First page: 24
      Abstract: Although there are existing vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), new COVID-19 cases are increasing due to low immunization coverage and the emergence of new variants. For this reason, new drugs to treat and prevent severe COVID-19 are needed. Here, we provide four different FDA-approved drugs against SARS-CoV-2 proteins involved in the entry and replication process, aiming to identify potential drugs to treat COVID-19. We use the main protease (Mpro), the spike glycoprotein (S protein), and RNA-dependent RNA polymerase (RdRp) as protein targets for anti- SARS-CoV-2 drugs. In our constructed database, we selected different drugs against each target (Mpro, S protein, and RdRp) based on their common interactions with relevant residues involved in viral entry at the host cell and replication. Furthermore, their stability inside the binding pocket, as well as their predicted binding-free energy, allow us to provide new insight into the possible drug repurposing of viomycin (interacting with Mpro) due to its interactions with key residues, such as Asn 143, Glu 166, and Gln 189 at the same time as hesperidin (interacting with the S protein) is interacting with residues Tyr 449, Ser 494, and Thr 500, keeping inside the predicted binding pocket, as well as interacting with residues in different variants of concern. Finally, we also suggest nystatin and elvitegravir (interacting with RdRp) as possible drugs due to their stability within the predicted pocket along the simulation and their interaction with key residues, such as Asp 760, Asp 761, and Asp 618. Altogether our results provide new knowledge about the possible mechanism of the inhibition of viomycin, hesperidin, elvitegravir, and nystatin to inhibit the viral life cycle of SARS-CoV-2 and some of its variants of concern (VOC). Additionally, some iodide-based contrast agents were also found to bind the S protein strongly, i.e., iohexol (−58.99 Kcal/mol), iotrolan (−76.19 Kcal/mol), and ioxilan (−62.37 Kcal/mol). Despite the information we report here as the possible strong interaction between these contrast agents and the SARS-CoV-2′s S protein, Mpro, and RdRp, we believe that further investigation, including chemical modifications in their structures, are needed for COVID-19 treatment.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-04-14
      DOI: 10.3390/scipharm90020024
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 25: Compounding in Ukraine: Assessment of the
           Risks for the Ointment’s Quality by the FMECA Method

    • Authors: Lesia Savchenko, Yuri Pidpruzhnykov, Roman Lesyk, Liudas Ivanauskas, Alla Kotvitska, Victoriya Georgiyants
      First page: 25
      Abstract: The level of compounded medicines (CM) quality has always been questioned in different countries. This problem has been resolved by the introduction of quality assurance system (QAS) standards. One of its main areas of significance is the risks assessment process, which is especially important for the compounding pharmacy according to the requirements of different international documents. Since ointments constitute a large part of CM, quantity assessment of risks for their quality by the FMECA method has been completed. During the first step of the research, 42 potential deviations of compounded ointments (CO) quality were identified. Via the questioning of compounding pharmacies specialists in different regions of Ukraine by a pre-developed ten-point scale, the severity of deviations consequence, their occurrence probability, and detecting possibility were determined followed by the calculation of the priority risk number (PRN) value. The Pareto analysis showed that nine possible CO quality defects represented 21% of their total number. Defects related to the composition or technology of ointments (29%) and their compliance with microbiological purity requirements (23%) had the largest percentage contribution to the total PRN value. It was also found that the deviations consequence had the most serious impact on the CO quality, due to their direct influence on patient health.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-04-19
      DOI: 10.3390/scipharm90020025
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 26: Binding of GS-461203 and Its Halogen
           Derivatives to HCV Genotype 2a RNA Polymerase Drug Resistance Mutants

    • Authors: Muhammad Arba, Setyanto Tri Wahyudi, Muhammad Sulaiman Zubair, Dylan Brunt, Mursalin Singh, Chun Wu
      First page: 26
      Abstract: Hepatitis C Virus (HCV) is reported to develop GS-461203 resistance because of multiple mutations within the RNA-dependent RNA Polymerase (RdRp) of HCV. The lack of a high-resolution structure of these RdRp mutants in complex with GS-461203 hinders efforts to understand the drug resistance. Here we decipher the binding differences of GS-461203 in the wild type and mutated systems T179A or M289L of HCV RdRp Genotype 2a using homology modeling, molecular docking, and molecular dynamics simulation. Key residues responsible for GS-461203 binding were identified to be Arg48, Arg158, Asp318, Asp319, and Asp220, and that mutations T179A or M289L have caused conformational changes of GS-461203 in the RdRp active site. The affinities of GS-461203 were reduced in T179A system, but it became slightly stronger in the M289L system. Furthermore, we designed two new analogues of GS-461203 which encouragingly induced more stable interactions than GS-461203, and thus resulted in much better binding energies. This present study reveals how a single mutation, T179A or M289L, will modulate GS-461203 binding in HCV RdRp Genotype 2a, while introducing two novel analogues to overcome the drug resistance which may be good candidate for further experimental verification.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-04-21
      DOI: 10.3390/scipharm90020026
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 27: Purification of Andrographolide Methanolic
           Extract Using Molecularly Imprinted Polymer Prepared by Precipitation
           Polymerization

    • Authors: Wiwin Winingsih, Slamet Ibrahim, Sophi Damayanti
      First page: 27
      Abstract: Molecularly Imprinted Polymer (MIP) has a specific cavity in which the conformity of shape, size, and functionalities corresponds with its template molecule and has been widely used in separation processes. Therefore, this study aims to examine the application of MIP for the purification of andrographolide. The MIP was synthesized by precipitation polymerization using methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) as the functional monomer and cross-linker, andrographolide as a template, and acetonitrile:toluene (3:1) as porogen solvent. The results showed that the binding capacity of Synthesized MIP was 1.2486 mg/g, while the particle size was 295.5 nm with a polydispersity index of 0.064. Furthermore, the imprinting and selectivity factors were 1.148 and 12.37, respectively. The purification process by MIP increased the purity from 55.37 ± 0.69 to 94.94% ± 0.34, while the isolate characterization showed that purified andrographolide had a similar character compared to the standard.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-04-26
      DOI: 10.3390/scipharm90020027
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 28: Preclinical Safety Profile of an Oral
           Naringenin/Hesperidin Dosage Form by In Vivo Toxicological Tests

    • Authors: Carla Georgina Cicero-Sarmiento, Rolffy Ortiz-Andrade, Jesús Alfredo Araujo-León, Maira Rubí Segura-Campos, Priscila Vazquez-Garcia, Héctor Rubio-Zapata, Efrén Hernández-Baltazar, Victor Yañez-Pérez, Amanda Sánchez-Recillas, Juan Carlos Sánchez-Salgado, Emanuel Hernández-Núñez, Durcy Ruiz-Ciau
      First page: 28
      Abstract: We developed a naringenin–hesperidin molar mixture (MIX–160) with proven antihyperglycemic and vasorelaxant activity in preclinical studies. A solid dosage form was manufactured to improve the bioavailability properties. In the current study, we sought to evaluate the oral preclinical toxicity of the MIX–160 dosage form, which showed no mortality or significant changes in the body weight, food consumption and tissue/organ mass in rats. Three daily oral doses (50, 300 and 2000 mg/kg of MIX–160) were assayed for 28 days. The results showed no structural abnormalities in the histological analysis and no significant changes (p > 0.05) in the liver biochemical markers (total bilirubin, AST and ALT) compared to the control group. The above findings showed that the MIX–160 dosage form did not exhibit relevant toxic effects, which suggests its potential safety as a drug candidate for clinical studies.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-02
      DOI: 10.3390/scipharm90020028
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 29: Gossypol from Gossypium spp. Inhibits
           Helicobacter pylori Clinical Strains and Urease Enzyme Activity:
           Bioactivity and Safety Assessments

    • Authors: Miroslava Šudomová, Sherif T. S. Hassan
      First page: 29
      Abstract: This study investigates the inhibitory activities of gossypol, a natural polyphenolic compound from Gossypium spp., against Helicobacter pylori (HP) clinical strains and a urease enzyme that plays a key role in the pathogenesis of HP. Gossypol was detected to exhibit a bacteriostatic action against all the HP strains tested with minimum inhibitory concentration (MIC) values ranging from 3.51 to 4.14 µg/mL. The activity of HP urease (HPU) was efficiently impeded by gossypol with a 50% inhibitory concentration (IC50) value of 3.3 µM using an Electrospray Ionization–Mass Spectrometry (ESI-MS)-based method. The in vitro cytotoxicity assay showed no significant cytotoxic properties of gossypol against human gastric epithelial cells. Additionally, molecular docking studies were performed to assess the binding mode and the molecular interactions of gossypol with HPU with a binding affinity value of −8.1 kcal/mol compared with an HPU–acetohydroxamic acid (a standard urease inhibitor) docking complex (–6.1 kcal/mol). The overall results reveal that gossypol might help fight against HP infection by two mechanisms of action: inhibition of the growth of HP and inhibition of urease.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-05
      DOI: 10.3390/scipharm90020029
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 30: Cinnamomum bejolghota Extract Inhibits
           Colorectal Cancer Cell Metastasis and TGF-β1-Induced
           

    • Authors: Athicha Kittiwattanokhun, Sukanda Innajak, Etsu Tashiro, Masaya Imoto, Ramida Watanapokasin
      First page: 30
      Abstract: Cinnamomum bejolghota, used in Thai traditional medicine remedies, has several biological activities including antimicrobial, antifungal, and anticancer. In colorectal cancer, epithelial-mesenchymal transition (EMT) is an initial step of cancer metastasis. Thus, this study investigated the effects of C. bejolghota bark extract (CBE) on colorectal cancer cell metastasis and transforming growth factor-β1 (TGF-β1) induced EMT in LoVo cells. The results showed that CBE could reduce cell migration, invasion, and adhesion of LoVo cells in a dose-dependent manner. In addition, our studies also showed that CBE could reverse TGF-β1-induced morphological changes as well as increase an epithelial marker, E-cadherin, while the expression of the mesenchymal marker, N-cadherin, was decreased in TGF-β1-treated LoVo cells. MMP-2 expression was effectively decreased but TIMP-1 and TIMP-2 expression was increased by the CBE treatment in LoVo cells. CBE also inhibited Smad2/3 phosphorylation and nuclear translocation as well as decreased the expression of Snail, Slug, and TCF8/ZEB1 transcription factors in LoVo cells. Moreover, CBE could inhibit TGF-β1-induced Smad-independent signaling pathway by decreased phosphorylation of ERK1/2, p38, and Akt. These findings suggest that CBE inhibited TGF-β1-induced EMT in LoVo cells via both Smad-dependent and Smad-independent pathways. Therefore, CBE may function as an alternative therapeutic treatment for colorectal cancer metastasis.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-09
      DOI: 10.3390/scipharm90020030
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 31: Antifungal and Modulatory Activity of
           Lemon Balm (Lippia alba (MILL.) N. E. BROWN) Essential Oil

    • Authors: Gleilton Sales, Suelen Medeiros, Igor Soares, Tiago Sampaio, Mary Bandeira, Nádia Nogueira, Maria Queiroz
      First page: 31
      Abstract: Fungal diseases and the progressive development of resistance are a challenge. In this context, Lippia alba (lemon balm) is a species used in folk medicine, being described with antimicrobial potential. The aim of this study was to determine the antifungal activity and modulating effect of the essential oil of Lippia alba (Mill.) N.E. Brown leaves (LaEO). The antifungal activity of LaEO on eight Candida strains was determined by minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC), minimum biofilm inhibition concentration (MBIC), minimum biofilm eradication concentration (MBEC) and time-kill. The checkerboard technique was used to determine the modulating effect of LaEO on antifungal activity. The results indicate the presence of 11 constituents, with a predominance of carvone (58.15%) and limonene (25.37%). LaEO was able to inhibit the growth of all tested microorganisms, with MIC and MLC ranging from 0.078 to 1.25 mg/mL and MBIC and MBEC ranging from 0.156 to 5 mg/mL. The time-kill assay showed that LaEO was able to eliminate the strains after two hours of exposure and the best association was observed for the combination of LaEO and ketoconazole. The results of the study indicate that LaEO has excellent antifungal activity with potential biotechnological application.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-11
      DOI: 10.3390/scipharm90020031
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 32: Comparison of the Purity and Impurity of
           Glucagon-for-Injection Products under Various Stability Conditions

    • Authors: Zhongli Bao, Ya-Chi Cheng, Mary Ziping Luo, Jack Yongfeng Zhang
      First page: 32
      Abstract: Glucagon is a polypeptide hormone that serves as an essential therapeutic agent in the emergency treatment of hypoglycemia. Recently, the first generic glucagon for injection was approved. However, unlike its brand name counterpart, which is produced via recombinant DNA, the generic glucagon is produced using a chemical synthesis method. Regardless of its origin, impurities may occur in both glucagon drug products. While these impurities may greatly compromise the safety and efficacy of the glucagon drug products, studies accessing the impurities of glucagon for injection are limited. This manuscript analyzed the stability and impurities of a generic and brand glucagon for injection, including desamido and non-desamido impurities, under various storage and temperature conditions using an ultra-performance liquid chromatography method. The glucagon products were analyzed after 6 and 24 months of storage under room temperatures (20–25 °C). In addition, the products were also assessed after 6 months of storage under high temperatures (40 °C). Under each stability storage condition, three lots of the synthetic glucagon were evaluated by UPLC with at least one lot of the recombinant glucagon for comparison. A total of 37 peaks were identified (except for the solvent peaks, which appeared at retention times less than 1.5 min) from the synthetic and recombinant glucagon lots. It was found that the number of impurities observed in the synthetic glucagon were lower than the referenced recombinant glucagon across all stability conditions. Throughout all tested conditions, the synthetic glucagon for injection had an averaged purity of 92.8–99.3%, while the referenced recombinant drug had an averaged purity of 70.3–91.7%. Based on the study results, it can be concluded that the impurity profile for the synthetic glucagon for injection has a comparable and even lower level of impurities than the recombinant version under all stability conditions.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-17
      DOI: 10.3390/scipharm90020032
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 33: Quality and In Vivo Assessment of a Fulvic
           Acid Complex: A Validation Study

    • Authors: Rahmuddin Khan, Pooja Jain, Foziyah Zakir, Mohd Aqil, Sameer Alshehri, Mohd Aamir Mirza, Zeenat Iqbal
      First page: 33
      Abstract: The present work aimed to re-assess the bioavailability enhancement potential of fulvic acid (FA). Carbamazepine (CBZ) and peat were used as a model drug and FA source, respectively. Our group has already evaluated the bioavailability enhancement potential of a less commercially viable source of FA, i.e., shilajit. In the present work, the phase solubility of CBZ was analyzed with varying concentrations of peat-sourced FA (2–12% w/v). The prepared complex (CBZ-FA) was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Dissolution, pharmacokinetic, and pharmacodynamic studies were also carried out. The results showed the presence of an interaction between the drug and FA within the complex, which led to 98.99 ± 2.0% enhancement in drug solubility. The results also showed 79.23 ± 2.1% dissolution of the complexed drug over 60 min and 69.32 ± 2.2% permeation from the intestinal gut sac over 90 min, which led to a significant enhancement of bioavailability and a reduction in the duration of epileptic seizures. Thus, this study re-authenticates our earlier results and suggests switching the FA source (shilajit to peat) for commercial product development.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-19
      DOI: 10.3390/scipharm90020033
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 34: Quality by Design: A Suitable Methodology
           in Industrial Pharmacy for Costa Rican Universities

    • Authors: Luis Castillo-Henríquez, Brayan Murillo-Castillo, Lexi Chaves-Siles, Juan José Mora-Román, Nils Ramírez-Arguedas, Édgar Hernández-Mora, José Vega-Baudrit
      First page: 34
      Abstract: This review aims to present the Quality by Design (QbD) model as a suitable methodology to perform research in the academic Costa Rican institutions that teach Pharmacy. Pubmed, Science Direct, and Google Scholar databases were screened for original research papers and review papers published not more than ten years ago. Institutional repositories from the different universities were reviewed as well. The QbD model stands out as a great methodology for carrying out research projects regarding Pharmaceutical Sciences, but especially for Industrial Pharmacy, where it has contributed in terms of formulation development, manufacturing, and quality control. Academic research based on this model enables the training and development of practical, scientific, and leadership skills in Industrial Pharmacy students. The generated knowledge can be shared in classrooms, which represents an ideal environment to communicate research results and to foster collaborative work between researchers, professors, and students. Moreover, research performed through a QbD approach increases the confidence shown by the industrial sector and health regulatory authorities in the quality of the research, products, and knowledge that are developed and created in an Academy. As a result, the implementation of the model has allowed the creation, transfer, and materialization of knowledge from the Costa Rican Academy to different local pharmaceutical industries.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-19
      DOI: 10.3390/scipharm90020034
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 35: Concepts for New Rapid Simple HPLC Method
           for Quantification of Fosfomycin Trometamol in Pharmaceutical Dosage Forms
           with Direct UV Detection

    • Authors: Marjan Piponski, Tanja Bakovska Stoimenova, Tetiana Melnyk, Sergiy Kovalenko, Elena Lazarevska Todevska, Marjan Velkovski, Sami El Deeb, Yuriy Mysula, Liliya Logoyda
      First page: 35
      Abstract: Two different concepts for developing direct HPLC-UV methods for quantifying fosfomycin trometamol were developed without any derivatization and modification of the analyte. In the first concept, without the use of alkylamines as ion-pairs in the mobile phase, by using cyanopropyl CN and a strong anion-exchanger column, we investigated the possibility of their highly polar and anion-exchanging forces and mechanisms to retain, separate and detect trometamol without the help of additional agents or modifiers. In the second concept, the most frequent reversed-phase C18 columns with different characteristics and vendors were tested in combination with different length-based alkylamines with 3–10 C atoms in their chains. In our research, we found that the ion-pairing of fosfomycin with 6–10 C-atom-based alkyl-length of aliphatic chains manifested the most appropriate strength of interactions between alkyl-paired trometamol molecules and octadecylsilane or C18 bonded RP column to achieve optimal retention, selectivity and peak shape on chromatograms, with the possibility for the fine-tuning of elution time. The simplicity of our method concept omits the need for expensive and sophisticated columns like HILIC, C30 graphite carbon, and mixed-mode-based columns for easier retaining, separation, and determination of fosfomycin, and for its quantification purposes, especially in high-throughput analyses in regular quality-control laboratories.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-24
      DOI: 10.3390/scipharm90020035
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 36: Optimized Methods for Analytical and
           Functional Comparison of Biosimilar mAb Drugs: A Case Study for Avastin,
           Mvasi, and Zirabev

    • Authors: Büşra Gürel, Eda Çapkın, Ayhan Parlar, Aylin Özkan, Meltem Çorbacıoğlu, Duygu Emine Dağlikoca, Meral Yüce
      First page: 36
      Abstract: Bevacizumab is a humanized therapeutic monoclonal antibody used to reduce angiogenesis, a hallmark of cancer, by binding to VEGF-A. Many pharmaceutical companies have developed biosimilars of Bevacizumab in the last decade. The official reports provided by the FDA and EMA summarize the analytical performance of biosimilars as compared to the originators without giving detailed analytical procedures. In the current study, several key methods were optimized and reported for analytical and functional comparison of bevacizumab originators (Avastin, Altuzan) and approved commercial biosimilars (Zirabev and Mvasi). This case study presents a comparative analysis of a set of biosimilars under optimized analytical conditions for the first time in the literature. The chemical structure of all products was analyzed at intact protein and peptide levels by high-resolution mass spectrometry; the major glycoforms and posttranslational modifications, including oxidation, deamidation, N-terminal PyroGlu addition, and C-terminal Lys clipping, were compared. The SPR technique was used to reveal antigen and some receptor binding kinetics of all products, and the ELISA technique was used for C1q binding affinity analysis. Finally, the inhibition performance of the samples was evaluated by an MTS-based proliferation assay in vitro. Major glycoforms were similar, with minor differences among the samples. Posttranslational modifications, except C-terminal Lys, were determined similarly, while unclipped Lys percentage was higher in Zirabev. The binding kinetics for VEGF, FcRn, FcγRIa, and C1q were similar or in the value range of originators. The anti-proliferative effect of Zirabev was slightly higher than the originators and Mvasi. The analysis of biosimilars under the same conditions could provide a new aspect to the literature in terms of the applied analytical techniques. Further studies in this field would be helpful to better understand the inter-comparability of the biosimilars.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-05-31
      DOI: 10.3390/scipharm90020036
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 37: Ex Vivo and In Vivo Study of Some
           Isoquinoline Precursors

    • Authors: Miglena Milusheva, Vera Gledacheva, Margarita Batmazyan, Stoyanka Nikolova, Iliyana Stefanova, Darinka Dimitrova, Kremena Saracheva, Desislav Tomov, Veneta Chaova-Gizdakova
      First page: 37
      Abstract: This article concerns the synthesis and biological activities of some N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides as isoquinoline precursors and compounds with smooth muscle (SM) relaxant activity. Aim: find the biological activity of N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides and compare it with papaverine, an isoquinoline alkaloid that has been known as a brain and coronary vasodilator and SM relaxant. Materials and methods: In silico simulation with the PASS online program predicts SM relaxant activity for the compounds. The amides were tested on the isolated gastric SM preparations (SMPs) from rats to determine their effects on spontaneous contractile activity (CA) compared with papaverine. The in vivo effect on the learning and memory processes of rats was also assessed. Results: the data from the isometric measurements showed that one of the compounds caused ex vivo relaxation in circular SM tissues isolated from the stomach (corpus) of male Wistar rats. Conclusion: We found that the compound’s SM relaxation uses the papaverine pathway. It also has an improving effect on the cognitive functions of learning and memory processes in rats.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-06-13
      DOI: 10.3390/scipharm90020037
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 38: In Vitro and In Silico Antistaphylococcal
           Activity of Indole Alkaloids Isolated from Tabernaemontana cymosa Jacq
           (Apocynaceae)

    • Authors: Yina Pájaro-González, Julián Cabrera-Barraza, Geraldine Martelo-Ramírez, Andrés F. Oliveros-Díaz, Juan Urrego-Álvarez, Wiston Quiñones-Fletcher, Fredyc Díaz-Castillo
      First page: 38
      Abstract: The species of the genus Tabernaemontana have a long tradition of use in different pathologies of infectious origins; the antibacterial, antifungal, and antiviral effects related to the control of the pathologies where the species of this genus are used, have been attributed to the indole monoterpene alkaloids, mainly those of the iboga type. There are more than 1000 alkaloids isolated from different species of Tabernaemontana and other genera of the Apocynaceae family, several of which lack studies related to antibacterial activity. In the present study, four monoterpene indole alkaloids were isolated from the seeds of the species Tabernaemontana cymosa Jacq, namely voacangine (1), voacangine-7-hydroxyindolenine (2), 3-oxovoacangine (3), and rupicoline (4), which were tested in an in vitro antibacterial activity study against the bacteria S. aureus, sensitive and resistant to methicillin, and classified by the World Health Organization as critical for the investigation of new antibiotics. Of the four alkaloids tested, only voacangine was active against S. aureus, with an MIC of 50 µg/mL. In addition, an in silico study was carried out between the four isolated alkaloids and some proteins of this bacterium, finding that voacangine also showed binding to proteins involved in cell wall synthesis, mainly PBP2 and PBP2a.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-06-14
      DOI: 10.3390/scipharm90020038
      Issue No: Vol. 90, No. 2 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 5: A New Practice to Monitor the Fabrication
           Process of Fab-Targeting Ligands from Bevacizumab by LC-MS: Preparation
           and Analytical Characterization

    • Authors: Franck Marquet, Valentina D’Atri, Davy Guillarme, Gerrit Borchard
      First page: 5
      Abstract: The objective of this study was to qualitatively evaluate a Fab-targeting ligand preparation containing free thiol groups in the hinge region by using bevacizumab as a model. The evaluation focused on the purification of fragments through a nonaffinity-based process using a centrifugal ultrafiltration technique and mild reduction conditions for the intact production of F(ab’) fragments with specific inter-heavy-chain disulfide bonds cleavage. Under these conditions, F(ab’) fragments with a defined chemical composition were successfully obtained via proteolytic digestion followed by a controlled reduction reaction process maintaining the integrity of the binding sites. The ultrafiltration purification technique appears to be suitable for the removal of the digestive enzyme but inefficient for the removal of Fc fragments, thus requiring additional processing. A suitable analytical strategy was developed, allowing us to demonstrate the reformation of disulfide bridges between the two reduced cysteines within F(ab’) fragments.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-01-04
      DOI: 10.3390/scipharm90010005
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 6: Dehydroepiandrosterone (DHEA) Improves the
           Metabolic and Haemostatic Disturbances in Rats with Male Hypogonadism

    • Authors: Sally M. Safwat, Abdelaziz M. Hussein, Elsayed A. Eid, Mohamed S. Serria, Basem H. Elesawy, Hussein F. Sakr
      First page: 6
      Abstract: Objectives: The current work was designed to study the effect of dehydroepiandrosterone (DHEA) on glucose homeostasis, liver functions and hemostatic disturbances in a rat model of bilateral orchidectomy (ORCH). Methods: 32 male rats (n = 8) were randomly assigned into 4 groups; (i) control (sham operated) group; were normal rats in which all surgical procedures were done without ORCH, (ii) Control + DHEA group: as control group but rats were treated with DHEA for 12 weeks, (iii) orchiectomized (ORCH) group: rats had bilateral orchidectomy and (iv) ORCH + DHEA group: orchiectomized rats treated with DHEA for 12 weeks. Four weeks after ORCH, DHEA treatment began and lasted for twelve weeks. By the end of the experiment, the parameters of glucose homeostasis, lipid profile, liver enzymes, bleeding and clotting times (B.T. and C.T.), prothrombin time (P.T.), activated partial thromboplastin time (aPTT), platelet count and aggregation, von-Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor (PAI-1), fibrin degradation products (FDP), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelin-1 were measured. Results: ORCH caused significant deteriorations in the parameters of glucose homeostasis, lipid profile, and liver functions (p < 0.05). In addition, lower androgenicity-induced by ORCH caused a significant rise in PAI-1, fibrinogen, FDPs, ET-1 (p < 0.01) with significant shortening of bleeding and clotting times. DHEA replacement therapy significantly decreased glucose, insulin, PAI-1, fibrinogen, ICAM-1, and VCAM-1 when compared to ORCH rats. Conclusion: DHEA ameliorated the metabolic, hepatic, hypercoagulable, and hypofibrinolysis disturbances induced by ORCH.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-01-20
      DOI: 10.3390/scipharm90010006
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 7: Antineoplastic Activity of Water-Soluble
           Form of Novel Kinase Inhibitor
           1-(4-Chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione
           immobilized on Polymeric Poly(PEGMA-co-DMM) Carrier

    • Authors: Nataliya Finiuk, Olga Klyuchivska, Nataliya Mitina, Halyna Kuznietsova, Kateryna Volianiuk, Alexander Zaichenko, Volodymyr Rybalchenko, Rostyslav Stoika
      First page: 7
      Abstract: The maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione (MI-1) was synthesized as inhibitor of several protein kinases, however, its application is hindered by its poor water solubility. In this study, the mechanisms of the antineoplastic action of MI-1 and its MI-1/M5 complex with M5 carrier (poly (PEGMA-co-DMM)) towards human colon carcinoma HCT116 cells were investigated by using the MTT and clonogenic assays, DNA intercalation with methyl green replacement, alkaline DNA comet assay, and Western-blot analysis. MI-1 compound and its MI-1/M5 complex possessed high toxicity towards colon (HCT116), cervical (HeLa) carcinoma cells and melanoma (SK-MEL-28) cells with GI50 value in a range of 0.75–7.22 µg/mL, and demonstrated high selectivity index (SI ˃ 6.9). The p53 status of colon cancer cells did not affect the sensitivity of these cells to the treatment with MI-1 and its MI-1/M5 complex. M5 polymer possessed low toxicity towards studied cells. The MI-1, MI-1/M5, and M5 only slightly inhibited growth of the pseudo-normal HaCaT and Balb/c 3T3 cell lines (GI50 ˃ 50 μg/mL). The MI-1 and its MI-1/M5 complex induced mitochondria-dependent pathway of apoptosis, damage of the DNA, and morphological changes in HCT116 cells, and affected the G2/M transition checkpoint. The MI-1 intercalated into the DNA molecule, while such capability of MI-1/M5 complex and M5 polymer was much lower. Thus, poly (PEGMA-co-DMM) might be a promising carrier for delivery of the maleimide derivative, MI-1, a novel kinase inhibitor, through improving its solubility in aqueous media and enhancing its antiproliferative action towards human tumor cells. Studies are in progress on the treatment of Nemeth-Kellner lymphoma (NK/Ly)-bearing mice with the MI-1 and MI-1/M5 complex.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-01-21
      DOI: 10.3390/scipharm90010007
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 8: Pharmacokinetic Study of Mucoadhesive
           Itopride Hydrochloride In Situ Nasal Gel Formulations in a Comparative In
           Vivo Study and Histopathological Safety Evaluation

    • Authors: Maha A. Marzouk, Dina A. Osman, Amany I. Abd El-Fattah, Reem A. Aldeeb
      First page: 8
      Abstract: Hepatic first-pass metabolism has been a major cause of reduced bioavailability for many drugs. Using the nasal route as an alternative route to deliver drugs to the systemic circulation provided the solution to this problem. One of the drugs which are highly affected by first-pass metabolism is itopride hydrochloride (ITO HCl). It is a prokinetic agent used for the treatment of various gastrointestinal motility disorders, mainly gastroesophageal reflux. The objective of this study was to determine the pharmacokinetic parameters of selected mucoadhesive in situ nasal gel formulations (F1 and F17) of itopride hydrochloride (ITO HCl) and to evaluate their safety after topical application on the nasal mucosa. The tested formulations contained 18% w/v poloxamer 407 with 0.5% w/v of HPMC K4M (F1), or with 0.5% w/v MC (F17). A randomized cross-over study was done on six rabbits after administration of F1, F17, and commercial oral tablets (Ganaton®). Plasma levels were assessed using high-performance liquid chromatography (HPLC) to compare the nasal gel formulations with the conventional oral tablets. Histopathological study of the nasal mucosa was performed in rats after nasal application of both in situ gel formulas. The in vivo pharmacokinetic profiles of in situ nasal gel formulas F1 and F17 provided showed improvement in Cmax, Ke, t1/2, AUC0–24, AUC24–inf, AUC0–inf, AUMC24–inf, AUMC0–inf, MRT, Vd, and Cmax/AUC0–24 values over commercial tablets (p < 0.05). No statistically significant difference was found between both nasal gel formulas (F1 and F17). The percentage relative bioavailability of ITO HCl nasal in situ gel F1 and F17 was found to be 171.22% and 178.91%, respectively, in comparison with the commercial tablet. Histopathological study of the nasal mucosa revealed the safety of nasal in situ gel formulations to the nasal mucosa after 14 days of application. The study showed that the formulation of itopride hydrochloride as a mucoadhesive in situ nasal gel has enhanced the drug bioavailability due to avoidance of first-pass metabolism. The study points to the potential of mucoadhesive nasal in situ gel in terms of safety and efficiency.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-01-21
      DOI: 10.3390/scipharm90010008
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 9: Acknowledgment to Reviewers of Scientia
           Pharmaceutica in 2021

    • Authors: Scientia Pharmaceutica Editorial Office Scientia Pharmaceutica Editorial Office
      First page: 9
      Abstract: Rigorous peer-reviews are the basis of high-quality academic publishing [...]
      Citation: Scientia Pharmaceutica
      PubDate: 2022-01-27
      DOI: 10.3390/scipharm90010009
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 10: Antioxidant Activity, Sun Protection
           Activity, and Phytochemical Profile of Ethanolic Extracts of Daemonorops
           acehensis Resin and Its Phytosomes

    • Authors: Rita Kartika Sari, Yanico Hadi Prayogo, Salman Arib Rozan, Mohamad Rafi, Ietje Wientarsih
      First page: 10
      Abstract: Daemonorops (Indonesian: jernang) resin is one of Indonesia’s leading non-timber forest products and can be developed as a source of natural antioxidants and sun protection. This study aimed to select promising solvents for extracting a Daemonorops acehensis resin and phytosome formulation with high antioxidant capacities and sun protection factor (SPF) values. Jernang resin was extracted using a water–ethanol mixture in five different ratios. The promising extract was then mixed with soy lecithin in three different formulations. A promising extract and phytosome were then selected based on their antioxidant capacities and sun protection factor (SPF) values. A liquid chromatography mass spectrometry/mass spectrometry (LC–MS/MS) analysis was also performed on five extracts to identify the components in the extracts that might be responsible for the biological activity. The results showed that the ethanol solvent variation and phytosome formulation influenced the antioxidant capacity and SPF value. A hundred-percent ethanolic extract and F1 phytosome exhibited the highest antioxidant capacities and SPF values. A qualitative analysis revealed the various classes of compounds in the extract and phytosome. A flavylium chromophore, dracorhodin, dominated the resin extract and was presumed to be the marker compound responsible for their antioxidant capabilities and SPF values. These findings are important for manufacturing sunscreens containing active compounds of bioactive natural resins.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-02-03
      DOI: 10.3390/scipharm90010010
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 11: Proof-of-Concept Preclinical Use of
           Drosophila melanogaster in the Initial Screening of Immunomodulators

    • Authors: Firzan Nainu, Muh. Akbar Bahar, Sartini Sartini, Reski Amalia Rosa, Nur Rahmah, Reski Amelia Kamri, Nur Rahma Rumata, Risfah Yulianty, Elly Wahyudin
      First page: 11
      Abstract: Drug discovery is a complex process, and the use of a comprehensive approach is deemed necessary to discover new chemical entities with novel mechanisms of action. This research was carried out to determine whether Drosophila melanogaster can serve as an appropriate model organism in the initial screening of drug candidates with immunomodulatory activities. To test this, we performed phenotypic assay and molecular analysis to investigate the immunomodulatory activities of aspirin, dexamethasone, curcumin, and epigallocatechin gallate (EGCG), that have been reported to yield such effects in the mammalian model system. In vivo survival analysis demonstrated that all drugs/compounds were relatively safe at the tested concentrations. In the infection assay, curcumin and EGCG showed a protective signature to bacterial infection in flies lacking Toll-mediated immune responses. Furthermore, dexamethasone and aspirin, drugs with immunosuppressive activity, could improve the survival of PGRP-LBΔ mutant flies with hyperactivated immune system. These phenotypes were supported by RT-qPCR-based molecular analysis, revealing that drugs/compounds used in this study could modulate the expression level of genes related to the immune system. In conclusion, while curcumin and EGCG could promote the improvement of fly survival against infection, aspirin and dexamethasone were able to suppress overactivation of immune responses in D. melanogaster. These results are in line with the ones observed in the mammalian model system, further emphasizing the notion that flies would serve as a prospective model organism in the initial screening of drug candidates for their immunomodulatory activities prior to further checking in the mammalian animal models. In the end, this will reduce the use of mammalian animal models for preliminary experiments in an effort to discover/repurpose drugs with immunomodulatory activity.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-02-08
      DOI: 10.3390/scipharm90010011
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 12: Repurposing of Anti-Malarial Drug
           Quinacrine for Cancer Treatment: A Review

    • Authors: Makhan Kumar, Angshuman Sarkar
      First page: 12
      Abstract: Quinacrine (QC), a synthetic drug belonging to the 9-aminoacridine family, has been used extensively to treat malaria and multiple ailments over the past several decades. Following its discovery in the 1920s and extensive use for the treatment of malaria for nearly two decades, numerous studies have explored its antineoplastic potential in both preclinical and clinical settings. Multiple studies spanning over seven decades have examined a wide range of QC anticancer activities across various types of cancers, along with the underlying mechanisms. Many of these mechanisms, including activation of the p53 signaling cascade and simultaneous NF-κB signaling inhibition, have been reported in various studies, bringing QC to a unique polypharmacological category drug possessing the potential to treat a wide variety of diseases, including cancer. This article summarizes most of the research conducted over several decades to uncover new molecular mechanisms activated or inactivated and directly correlate with antineoplastic activity QC.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-02-08
      DOI: 10.3390/scipharm90010012
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 13: Amphiphilic Alkylated Pectin Hydrogels for
           Enhanced Topical Delivery of Fusidic Acid: Formulation and In Vitro
           Investigation

    • Authors: Mohammad F. Bostanudin
      First page: 13
      Abstract: Hydrogels constructed of amphiphilically modified polysaccharides have attracted a lot of interest because of their potential to augment drug diffusion over the skin. This research describes the synthesis of amphiphilic alkylated pectin via glycidyl tert-butyl ether modification (alkylation degree 15.7%), which was characterized using spectroscopic and thermal analysis techniques and then formulated into hydrogels for the study of their potential in regulating fusidic acid diffusion topically. The hydrogels were formulated by the ionic interaction of negatively charged pectin and positively charged crosslinker CaCl2, with a reported fusidic acid loading degree of 93–95%. Hydrogels made of alkylated pectin showed a lower swelling percentage than that of native pectin, resulting in a slower fusidic acid release. The influence of pH on the swelling percentage and drug release was also investigated, with results revealing that greater pH enhanced swelling percentage and drug release. The in vitro interactions with HaCaT cells revealed negligible cytotoxicity under application-relevant settings. Utilizing Franz diffusion cells, the alkylated pectin hydrogels caused fusidic acid to penetrate the Strat-M® membrane at a 1.5-fold higher rate than the native pectin hydrogels. Overall, the in vitro results showed that alkylated pectin hydrogels have a lot of promise for topical distribution, which needs further investigation.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-02-14
      DOI: 10.3390/scipharm90010013
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 14: Systematic Review on the Effectiveness of
           Essential and Carrier Oils as Skin Penetration Enhancers in Pharmaceutical
           Formulations

    • Authors: Bahjat Alhasso, Muhammad Usman Ghori, Barbara R. Conway
      First page: 14
      Abstract: Oils, including essential oils and their constituents, are widely reported to have penetration enhancement activity and have been incorporated into a wide range of pharmaceutical formulations. This study sought to determine if there is an evidence base for the selection of appropriate oils for particular applications and compare their effectiveness across different formulation types. A systematic review of the data sources, consisting of Google Scholar, EMBASE, PubMed, Medline, and Scopus, was carried out and, following screening and quality assessment, 112 articles were included within the analysis. The research was classified according to the active pharmaceutical ingredient, dosage form, in vitro/in vivo study, carrier material(s), penetration enhancers as essential oils, and other chemical enhancers. The review identified four groups of oils used in the formulation of skin preparations; in order of popularity, these are terpene-type essential oils (63%), fatty acid-containing essential oils (29%) and, finally, 8% of essential oils comprising Vitamin E derivatives and miscellaneous essential oils. It was concluded that terpene essential oils may have benefits over the fatty acid-containing oils, and their incorporation into advanced pharmaceutical formulations such as nanoemulsions, microemulsions, vesicular systems, and transdermal patches makes them an attractive proposition to enhance drug permeation through the skin.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-02-19
      DOI: 10.3390/scipharm90010014
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 15: Formulation Optimization of Extemporaneous
           Oral Liquids Containing Naloxone and Propranolol for Pediatric Use

    • Authors: Maria Attebäck, Bengt Hedin, Sofia Mattsson
      First page: 15
      Abstract: There is a need to develop dosage forms suitable for children to improve drug treatment. Extemporaneous compounding of drugs for children is one way to meet these needs. However, excipients generally considered as safe in adults may not be appropriate in dosage forms intended for children. The aim was to optimize the composition of two pediatric liquid preparations by substituting paraben as a microbiological preservative and ethanol as a solubilizer, with excipients more suitable for pediatric use. The oral liquids were Naloxone 1 mg/mL and Propranolol 10 mg/mL. Twelve different formulations were tested with propranolol and naloxone, respectively, during the screening process to select appropriate formulations. Sodium benzoate and glycerol were used as a preservative and solubilizer, respectively, and different pH of the formulations were evaluated. The formulations were characterized according to dispensed dose (dosing accuracy), viscosity and osmolality. The optimized formulations from the screening process were tested with two amounts of sodium benzoate and microbiological assays were performed. These formulations were shown to have satisfactory preservative properties and dosing accuracy. The results showed that the oral liquids could be prepared without the addition of solubilizer and with lower osmolality (naloxone), thus reducing the risk of gastrointestinal side effects.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-02-22
      DOI: 10.3390/scipharm90010015
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 16: Compatibility of Different Formulations in
           TrichoConceptTM Vehicles for Hair Treatments

    • Authors: Hudson Polonini, Sarah Taylor, Clark Zander
      First page: 16
      Abstract: The wide variety of potential pathogeneses for alopecia and the wide variety of active pharmaceutical ingredients (APIs) to treat and manage those pathogeneses highlight the importance of the development of stable and effective topical treatments. Topical options for alopecia on the market remain limited and oral products may result in unwanted systemic adverse effects. This study is meant to fill the gap by determining compatibility in terms of beyond-use date (BUD) of APIs with theoretical or demonstrated benefits for topical use for alopecia. The compatibility of seven formulations was tested: F1 = clobetasol 0.05% in TrichoWashTM; F2 = ketoconazole 2% in TrichoWashTM; F3 = spironolactone 1% in TrichoWashTM; F4 = latanoprost 0.1% in TrichoCreamTM; F5 = pyridoxine HCl 0.5%, vitamin A acetate 1%, and vitamin E succinate 12.1 IU in TrichoCondTM; F6 = Caffeine 2%, menthol 1%, and pyridoxine HCl 0.5% in TrichoWashTM; F7 = Latanoprost 0.1%, minoxidil 5%, and finasteride 0.25% in TrichoSolTM. All formulations presented a BUD of 6 months, except for F4 and F7, which showed compatibility for 3 months. This validates the compatibility of the APIs with the TrichotechTM vehicles, and that they are highly convenient for compounding pharmacies.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-02-25
      DOI: 10.3390/scipharm90010016
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 17: Evaluation of Liposome-Loaded Microbubbles
           as a Theranostic Tool in a Murine Collagen-Induced Arthritis Model

    • Authors: Joke Deprez, Silke Roovers, Guillaume Lajoinie, Heleen Dewitte, Tine Decruy, Julie Coudenys, Benedicte Descamps, Christian Vanhove, Michel Versluis, Dirk Elewaut, Peggy Jacques, Stefaan C. De Smedt, Ine Lentacker
      First page: 17
      Abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe inflammation of the synovial tissue. Here, we assess the feasibility of liposome-loaded microbubbles as theranostic agents in a murine arthritis model. First, contrast-enhanced ultrasound (CEUS) was used to quantify neovascularization in this model since CEUS is well-established for RA diagnosis in humans. Next, the potential of liposome-loaded microbubbles and ultrasound (US) to selectively enhance liposome delivery to the synovium was evaluated with in vivo fluorescence imaging. This procedure is made very challenging by the presence of hard joints and by the limited lifetime of the microbubbles. The inflamed knee joints were exposed to therapeutic US after intravenous injection of liposome-loaded microbubbles. Loaded microbubbles were found to be quickly captured by the liver. This resulted in fast clearance of attached liposomes while free and long-circulating liposomes were able to accumulate over time in the inflamed joints. Our observations show that murine arthritis models are not well-suited for evaluating the potential of microbubble-mediated drug delivery in joints given: (i) restricted microbubble passage in murine synovial vasculature and (ii) limited control over the exact ultrasound conditions in situ given the much shorter length scale of the murine joints as compared to the therapeutic wavelength.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-02-28
      DOI: 10.3390/scipharm90010017
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 18: Purple Corn Silk Extract Attenuates
           UVB-Induced Inflammation in Human Keratinocyte Cells

    • Authors: Watcharaporn Poorahong, Sukanda Innajak, Malyn Ungsurungsie, Ramida Watanapokasin
      First page: 18
      Abstract: UVB is a causative factor for severe skin damage, such as cell aging, death, and inflammation. UVB easily permeates into the epidermis layer of human skin, which is mainly composed of keratinocyte cells. In previous results, we found that purple corn silk (PCS) extract showed the potential to inhibit keratinocyte damages of UVB-treated cells. Thus, in this study, we aimed to evaluate the preventive effects of PCS extract against the inflammation of UVB-induced keratinocyte cells using the HaCaT cell line. HaCaT cells were treated with PCS extract at various concentrations for 1 h, then exposed to 25 mJ/cm2 UVB before subsequent experiments. Fragmented DNA was observed using flow cytometry. The inflammatory response was investigated through NF-κB activity by immunofluorescence staining and related protein expression by Western blotting. The results demonstrated that PCS extract decreased the sub-G1 DNA content. Interestingly, PCS extract attenuated NF-κB activity via suppressed NF-κB nuclear translocation and protein expression. Moreover, PCS extract remarkably decreased c-Jun phosphorylation and decreased proinflammatory cytokines, along with iNOS and COX-2 levels in UVB-treated cells compared to the UVB-control group. This finding exhibited that PCS extract minimized inflammation in keratinocyte cells induced by UVB radiation.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-03-01
      DOI: 10.3390/scipharm90010018
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 19: Application of Quality by Design Approach
           to the Pharmaceutical Development of Anticancer Crude Extracts of Crocus
           sativus Perianth

    • Authors: Olha Mykhailenko, Liudas Ivanauskas, Ivan Bezruk, Vilma Petrikaitė, Victoriya Georgiyants
      First page: 19
      Abstract: The application of the Quality by Design (QbD) concept to extracts obtained from Crocus sativus perianth with potential anticancer activity will ensure the safety, efficiency, and quality control of the entire technological process, as well as determine the critical factors affecting the quality of extracts. Potentially critical points of the production of the plant extracts, including the cultivation and processing of the plant materials, the extraction process, and the choice of solvents, were identified using the Ishikawa diagram and FMEA risk assessment methods as well as the corrective actions proposed. The Herbal Chemical Marker Ranking System (HerbMars) approach was used to justify the Q-markers choice of Crocus, which takes into account bioavailability, pharmacological activity, and the presence of the selected standard. An experimental design (DoE) was used to assess the influence of potentially critical factors on the efficiency of the compound extraction from raw materials with water or ethanol. The presence of 16 compounds in Crocus perianth was determined by HPLC and their quantitative assessment was established. Selected compounds (ferulic acid, mangiferin, crocin, rutin, isoquercitrin) can be used for the quality control of Crocus perianth. In addition, the stigmas from the Volyn region met the requirements of ISO 3632 for saffron as a spice (category I). The cytotoxic activity against melanoma (IGR39) and triple-negative breast cancer (MDA-MB-231) cell lines of the hydroethanolic extract of C. sativus perianth was significantly more pronounced than the water extract, probably due to the chemical composition of the constituent components. The results show that the QbD approach is a powerful tool for process development for the production of quality herbal drugs.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-03-03
      DOI: 10.3390/scipharm90010019
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 20: Nanocarrier Systems in Taste Masking

    • Authors: Nasr Eldin Hussein Nasr, Aliaa Nabil ElMeshad, Ahmed Roshdy Fares
      First page: 20
      Abstract: Taste is the most crucial organoleptic parameter affecting patient compliance in the case of drugs with poor palatability. Taste masking is a major challenge for the development of orally ingested active pharmaceutical constituents in the pharmaceutical industry. Numerous conventional taste-masking techniques have been extensively studied. In parallel, affecting the drug solubility or release is a major concern of conventional taste-masking techniques. Recently, many nanocarrier systems have been introduced, claiming the advantage of effective taste masking without affecting either the drug solubility or its release. In this review, we will present new techniques for taste masking, including taste-masking techniques utilizing nanocarrier systems such as liposomes, polymeric and solid lipid nanoparticles, polymeric micelles, submicron lipid emulsions, and nanogels. We will chiefly highlight the composition of these systems and their applications in designing oral therapeutic delivery systems successful in masking the taste of bitter molecules.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-03-04
      DOI: 10.3390/scipharm90010020
      Issue No: Vol. 90, No. 1 (2022)
       
  • Sci. Pharm., Vol. 90, Pages 21: Temperature and pH-Dependent Behaviors of
           mAb Drugs: A Case Study for Trastuzumab

    • Authors: Fatma Sert, Defne Hız, Mert Gülmez, Selen Ezgi Cankurtaran, Cemre Irmak Kayalan, Hasan Kurt, Meral Yüce
      First page: 21
      Abstract: The distortions in the high-order structure of therapeutic monoclonal antibodies (mAbs) under different environmental conditions acutely affect mAb stability, resulting in altered safety, efficacy, and shelf-life profiles. The overall stability of mAbs depends on many factors, and it requires complementary techniques for an in-depth analysis. The stability of mAbs can be characterized by differential centrifugal sedimentation (DCS), differential scanning calorimetry (DSC), differential scanning fluorimetry (DSF), and size exclusion chromatography (SEC) techniques. In this report, temperature-ramped dynamic light scattering (DLS), and circular dichroism (CD) spectroscopy were employed as complementary tools to show how temperature and pH affect the aggregation of a model mAb, trastuzumab, in solution. The results showed that the aggregation onset temperature of trastuzumab defined by DLS was 75 °C, which decreases the amount of β-sheets and causes a slight increase in helix structures. Moreover, the melting temperature of trastuzumab was determined to be between 80–83 °C by temperature-ramped CD spectrophotometry, which is in line with the Tm of trastuzumab’s Fab region tested with DSC. Thus, unfolding and aggregation of trastuzumab start simultaneously at 75 °C, and unfolding triggers the aggregation. The temperature-ramped CD and DLS methods are robust tools to determine the thermal behavior of biosimilars in various solution conditions. Their complementary usage provides solid scientific background for regulatory applications and a better understanding of mAb instability and its relationship with structural changes.
      Citation: Scientia Pharmaceutica
      PubDate: 2022-03-21
      DOI: 10.3390/scipharm90010021
      Issue No: Vol. 90, No. 1 (2022)
       
 
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