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- Taste-masking methods in multiparticulate dosage forms with a focus on
poorly soluble drugs
Abstract: In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these methods often led to inconsistent dosing, resulting in under- or overdosing. To address this problem and promote adherence, numerous initiatives, and regulatory frameworks have been developed to develop more child-friendly dosage forms. In recent years, multiparticulate dosage forms such as mini-tablets, pellets, and granules have gained popularity. However, a major challenge that persists is effectively masking the bitter taste of drugs in such formulations. This review therefore provides a brief overview of the current state of the art in taste masking techniques, with a particular focus on taste masking by film coating. Methods for evaluating the effectiveness of taste masking are also discussed and commented on. Another important issue that arises frequently in this area is achieving sufficient dissolution of poorly water-soluble drugs. Since the simultaneous combination of sufficient dissolution and taste masking is particularly challenging, the second objective of this review is to provide a critical summary of studies dealing with multiparticulate formulations that are tackling both of these issues.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Sedative load and anticholinergic burden among older adults in Slovenia
over a decade: Potential for optimization of pharmacotherapy
Abstract: This study investigates the 10-year trend in the sedative and anticholinergic burden among older adults in Slovenia, with the aim of identifying opportunities to optimize pharmacotherapy in this population. A retrospective drug utilization analysis was conducted based on a national anonymized database of dispensed prescriptions from 2009 to 2019. The study employed the sedative load model and the anticholinergic cognitive burden scale to assess the sedative and anti cholinergic burden, respectively. The findings indicate that in 2019, 45.6 % and 40.8 % of older adults (≥ 65 years) used sedative and anticholinergic medications, respectively. A high sedative load and a clinically significant anticholinergic burden were observed in a considerable proportion of older adults (13.2 % and 11.2 %, respectively, in 2019). The age-standardized prevalence of sedative load and anti-cholinergic burden significantly decreased over the 10-year study period by 5.6 % and 1.7 %, respectively (absolute difference), while the prevalence of clinically significant anticholinergic burden remained stable. Notably, the age groups 85–89 years and above 90 years had an increase in the proportion of individuals with a clinically significant anticholinergic burden over the years. These results emphasize the need for targeted interventions, particularly in the oldest age groups, to promote safe and effective medication use among older adults.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Lyophilised protein formulations as a patient-centric dosage form: A
contribution toward sustainability paradigm
Abstract: At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising the development of patient-specific delivery systems and thus the provision of efficient and sustainable drugs. Protein drugs for subcutaneous administration, by allowing less frequent application, represent one of the most important parts of the pharmaceutical field, but their development is inevitably faced with obstacles in providing protein stability and suitable formulation viscosity. To gain further knowledge and fill the gaps in the already constructed data platform for the development of monoclonal antibody formulations, we designed a study that examines small model proteins, i.e., bovine serum albumin. The main aim of the presented work is to evaluate the effect of protein concentrations on critical quality attributes of both, pre-lyophilised liquid formulations, and lyophilised products. Through the study, the hypothesis that increasing protein concentration leads to higher viscosity and higher reconstitution time without affecting the stability of the protein was confirmed. The most important finding is that sucrose plays a key role in the lyophilisation of investigated protein, nevertheless, it can be predicted that, to ensure the beneficial effect of mannitol, its amount has to prevail over the amount of sucrose.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Lipid-based systems with precipitation inhibitors as formulation approach
to improve the drug bioavailability and/or lower its dose: a review
Abstract: Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the “spring and parachute” strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug’s bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (m/m). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Determination of remifentanil in neonatal dried blood spots by liquid
chromatography-tandem mass spectrometry
Abstract: Remifentanil is an ultra-short-acting synthetic opioid-class analgesic which might be increasingly used “off-label” as pain management during labour. Side effects in parturients during labour, and in the infant at birth are of particular concern, especially respiratory depression which is concentration-dependent, and can occur at levels as low as 3–5 ng mL–1. The safety of such use, particularly in newborns due to remifentanil placental transfer, has not been fully demonstrated yet, partly due to the lack of a suitable non-invasive analytical method. The aim of our work was to develop a sensitive method to monitor the levels of remifentanil in neonates by a non-invasive sampling of umbi lical cord blood to support efficacy and safety trials. The presented LC-MS method is sensitive enough to reliably quantify remifentanil in just 20 µL of blood at only 0.3 ng mL–1. The dried blood spot sample preparation included solvent extraction with subsequent solid-phase extraction. The method was validated in terms of accuracy, precision, recovery, matrix effect, and stability, and was successfully applied to a small pilot study. The estimated arterial blood concentrations at the time of delivery ranged from 0.2 to 0.3, and up to 0.9 ng mL–1 in neonatal, and maternal samples, respectively.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Population pharmacokinetics of ramipril in patients with chronic heart
failure: A real-world longitudinal study
Abstract: In patients with chronic heart failure (CHF), the use of angiotensin-converting enzyme inhibitors, including ramipril, is recommended to reduce the risk of heart failure worsening, hospitalisation, and death. Our aim was to investigate the influence of body composition on the pharmacokinetics of ramipril and its active metabolite ramiprilat and to evaluate the changes in pharmacokinetics after prolonged therapy. Twenty-three patients with CHF who were on regular therapy with ramipril participated at the first study visit ( median age 77 years, 65 % male, and 70 % New York Heart Association Class II); 19 patients attended the second study visit and the median time between the two visits was 8 months. Pharmacokinetics were assessed using a nonlinear mixed-effects parent-metabolite model comprising two compartments for ramipril and one compartment for ramiprilat. The influence of body size and composition was best described by an allometric relationship with fat-free mass. In addition, ramipril clearance was related to patient age and daily ramipril dose, while clearance of ramiprilat was influenced by glome rular filtration rate and daily ramipril dose. There were no clinically relevant changes in the pharmacokinetics of ramipril and ramiprilat between the study visits. Due to the relatively stable pharmacokinetics of ramipril, regular outpatient visits at 6-month intervals seem appropriate to evaluate ramipril therapy.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Forecasting the effect of water gastric emptying patterns on model drug
release in an glass-bead flow-through system
Abstract: Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an in vitro glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Clinical application of hempseed or flaxseed oil-based lyotropic liquid
crystals: Evaluation of their impact on skin barrier function
Abstract: The principal function of skin is to form an effective barrier between the human body and its environment. Impaired barrier function represents a precondition for the development of skin diseases such as atopic dermatitis (AD), which is the most common inflammatory skin disease characterized by skin barrier dysfunction. AD significantly affects patients’ quality of life, thus, there is a growing interest in the development of novel delivery systems that would improve therapeutic outcomes. Herein, eight novel lyotropic liquid crystals (LCCs) were investigated for the first time in a double-blind, interventional, before-after, single-group trial with healthy adult subjects and a twice-daily application regimen. LCCs consisted of constituents with skin regenerative properties and exhibited lamellar micro-structure, especially suitable for dermal application. The short- and long-term effects of LCCs on TEWL, SC hydration, erythema index, melanin index, and tolerability were determined and compared with baseline. LCCs with the highest oil content and lecithin/Tween 80 mixture stood out by providing a remarkable 2-fold reduction in TEWL values and showing the most distinctive decrease in skin erythema levels in both the short- and long-term exposure. Therefore, they exhibit great potential for clinical use as novel delivery systems for AD treatment, capable of repairing skin barrier function.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Deprescribing: An umbrella review
Abstract: This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with deprescribing intervention trials (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with medication cessation trials (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with deprescribing intervention trials. Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of medication cessation trials, a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- The potential of three-dimensional printing for pediatric oral solid
dosage forms
Abstract: Pediatric patients often require individualized dosing of medicine due to their unique pharmacokinetic and developmental characteristics. Current methods for tailoring the dose of pediatric medications, such as tablet splitting or compounding liquid formulations, have limitations in terms of dosing accuracy and palatability. This paper explores the potential of 3D printing as a solution to address the challenges and provide tailored doses of medication for each pediatric patient. The technological overview of 3D printing is discussed, highlighting various 3D printing technologies and their suitability for pharmaceutical applications. Several individualization options with the potential to improve adherence are discussed, such as individualized dosage, custom release kinetics, tablet shape, and palatability. To integrate the preparation of 3D printed medication at the point of care, a decentralized manufacturing model is proposed. In this setup, pharmaceutical companies would routinely provide materials and instructions for 3D printing, while specialized compounding centers or hospital pharmacies perform the printing of medication. In addition, clinical opportunities of 3D printing for dose-finding trials are emphasized. On the other hand, current challenges in adequate dosing, regulatory compliance, adherence to quality standards, and maintenance of intellectual property need to be addressed for 3D printing to close the gap in personalized oral medication.
PubDate: Thu, 30 May 2024 00:00:00 GMT
- Comparative effects of pravastatin and rosuvastatin on carbohydrate
metabolism in an experimental diabetic rat model
Abstract: Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg−1 day−1 doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg−1 day−1 reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg−1 day−1, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg−1 day−1, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg−1 day−1, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg−1 day−1 dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg−1 day−1 is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- A comprehensive overview of selective and novel fibroblast growth factor
receptor inhibitors as a potential anticancer modality
Abstract: The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- Furanocoumarin compounds isolated from potentiate irinotecan anticancer
activity against colorectal cancer cells
Abstract: Although the anticancer activity of Dorstenia foetida was already observed, the chemical entity responsible for this activity remained unidentified. In this study, the cytotoxic activity of two furanocoumarin compounds, i.e., 5-methoxy--3-(3-methyl-2,3-dihydroxybutyl)-psoralen (1) and 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate (2) isolated from ethyl acetate fraction of D. foetida (whole plant) was investigated in several cancer cell lines including HN22, MDA-MB-231, HCT116, and HT29. The results revealed that compound 2 exhibited cytotoxic activity, particularly against colorectal cancer cell lines HCT116 and HT29. The interplay between compound 2 and irinotecan (Iri) showed synergism against HCT116, which was analyzed by CompuSyn software. The simulation revealed that, at the molar ratio of Iri:2 of 1:40, the concentration predicted to achieve a 90 % inhibitory effect when used in the combination would be ~28- and ~4-fold lower than the concentration of compound 2 and Iri, resp., when used individually. Finally, the percentage of apoptotic cells in the HCT116 line treated with the combination was markedly higher than in the cells treated with the individual agent (60 % apoptotic cells for the combination compared to 17 and 45 % for Iri and compound 2 monotherapy, resp). In conclusion, our results identified compound 2 as a plant-derived compound exhibiting anticancer properties that can act synergistically with Iri and warranted further research to assess the potential of this synergism for colorectal cancer treatment.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- Chemical composition and potential antioxidant, anti-inflammatory, and
analgesic efficacy of L.
Abstract: This study aims to assess the chemical composition of the aqueous extract of Cistus albidus L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti--inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in C. albidus seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect in vivo, and albumin denaturation to evaluate the anti-inflammatory effect in vitro. The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic effi cacy in vivo.Chemical analysis was performed by UPLC-MS/MS to quantify several phenolic compounds including catechin (1,627.6 mg kg−1), quercitrin (1,235.8 mg kg–1) and gallic acid (628. 2 mg kg−1). The ICP analysis revealed that potassium and calcium were the main inorganic components in the seeds and leaves of C. albidus. The hydroethanolic extract of the leaves showed the highest content of polyphenols/flavonoids, whereas the highest value of proantho cyanidins was detected in the aqueous extract of the seeds. All extracts showed potent antioxidant activity related to different phenolic compounds (quercetin, gallic acid, astragalin, catechin, and rutin). The aqueous extract of the leaves strongly inhibited paw edema (76.1 %) after 6 h of treatment and showed maximal inhibition of protein denaturation (191.0 µg mL−1 for 50 % inhibition) and analgesic activity in different nociceptive models. The presented data reveal that C. albidus extracts potentially show antioxidant, anti-inflammatory, and analgesic activities that could confirm the traditional use of this plant.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- Characterization of mineral composition of leaves and flowers of
wild-growing
Abstract: The objective of this study was to determine the mineral content in the leaves and flowers of wild-grown Sambucus nigra collected from eleven different locations in Kosovo. The samples were digested in a microwave system using the wet digestion method. The minerals were determined by the application of inductively coupled plasma-atomic emission spectrometry (ICP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS). A total of 31 elements were determined, 15 elements by the ICP-AES method (Al, B, Ba, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, P, Sr, V, and Zn) and 16 elements by the ICP-MS method (Ag, As, Be, Bi, Cd, Co, Cs, Ga, Hg, In, Li, Ni, Pb, Rb, Tl, and U). The leaves of S. nigra show a higher content of minerals compared to the flowers, except for the flower of the sample SN-FL10, which is characterized by a high concentration of Fe, Al, Pb, Be, and Tl. The concentration of heavy metals and toxic elements (Pb, Cd, and Hg) was within the permissible concentrations according to Eur. Ph.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- Deguelin inhibits the proliferation of human multiple myeloma cells by
inducing apoptosis and G2/M cell cycle arrest: Involvement of Akt and p38
MAPK signalling pathway
Abstract: Deguelin exhibits antiproliferative activity against various cancer cell types. Previous studies have reported that deguelin exhibits pro-apoptotic activity against human cancer cells. The current study aimed at further elaborating the anticancer effects of deguelin against multiple myeloma cells. Cell growth estimations were made through MTT assay. Phase contrast microscopy was used for the analysis of the viability of multiple myeloma cells. Colony formation from multiple myeloma cells was studied using a clonogenic assay. Antioxidative assays for determining levels of glutathione (GSH) and superoxide dismutase (SOD) were carried out after treating multiple myeloma cells with deguelin. The apoptosis of multiple myeloma cells was studied using AO/EB and Annexin V-FITC/PI staining methods. Multiple myeloma cell cycle analysis was performed through flow cytometry. mRNA expression levels were depicted using qRT-PCR. Migration and invasion of multiple myeloma cells were determined with the wound-healing and transwell assays, respectively. Deguelin specifically inhibited the multiple myeloma cell growth while the normal plasma cells were minimally affected. Multiple myeloma cells when treated with deguelin exhibited remarkably lower viability and colony-forming ability. Multiple myeloma cells treated with deguelin produced more SOD and had higher GSH levels. The multiple myeloma cell growth, migration, and invasion were significantly declined by in vitro administration of deguelin. In conclusion, deguelin treatment, when applied in vitro, induced apoptotic cell death and resulted in mitotic cessation at the G2/M phase through modulation of cell cycle regulatory mRNAs in multiple myeloma cells.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- Medicarpin suppresses lung cancer cell growth and by inducing cell
apoptosis
Abstract: Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- Novel (±)---lactam ureas: Synthesis, and biological profiling
Abstract: A diastereomeric mixture of racemic 3-phthalimido-b-lactam 2a/2b was synthesized by the Staudinger reaction of carboxylic acid activated with 2-chloro-1-methylpyridinium iodide and imine 1. The amino group at the C3 position of the b-lactam ring was used for further structural upgrade. trans-b-lactam ureas 4a–t were prepared by the condensation reaction of the amino group of b-lactam ring with various aromatic and aliphatic isocyanates. Antimicrobial activity of compounds 4a–t was evaluated in vitro and neither antibacterial nor antifungal activity were observed. Several of the newly synthesized trans-b-lactam ureas 4a–c, 4f, 4h, 4n, 4o, 4p, and 4s were evaluated for in vitro antiproliferative activity against liver hepatocellular carcinoma (HepG2), ovarian carcinoma (A2780), breast adenocarcinoma (MCF7) and untransformed human fibroblasts (HFF1). The b-lactam urea 4o showed the most potent antiproliferative activity against the ovarian carcinoma (A2780) cell line. Compounds 4o and 4p exhibited strong cytotoxic effects against human non-tumor cell line HFF1. The b-lactam ureas 4a–t were estimated to be soluble and membrane permeable, moderately lipophilic molecules (logP 4.6) with a predisposition to be CYP3A4 and P-glycoprotein substrates. The tools PASS and SwissTargetPrediction could not predict biological targets for compounds 4a–t with high probability, pointing to the novelty of their structure. Considering low toxicity risk, molecules 4a and 4f can be selected as the most promising candidates for further structure modifications.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- Long non-coding RNA suppresses growth and epithelial-mesenchymal
transition by inhibiting Wnt/-catenin signaling pathway in human
pancreatic cancer PANC-1 cells: Insights from and studies
Abstract: There is increasing evidence that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of malignant tumors, particularly pancreatic cancer. In this study, the influence of the lncRNA TINCR on the behavior of human pancreatic cancer cells was investigated with the aim of deciphering its role in growth, migration, and invasion. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate TINCR expression in pancreatic cancer cells. Ectopic expression of TINCR in PANC-1 cells was induced to evaluate the effects on cell viability and apoptosis, examining the apoptotic genes Bax and Bcl-2. Migration and invasion assays were used to measure the impact of TINCR on these cellular processes. In vivo studies using a xenograft mouse model examined the effects of TINCR on tumor growth, epithelial-to-mesenchymal transition (EMT) markers, and the Wnt/β-catenin signaling pathway. PANC-1 cells showed strikingly low TINCR expression compared to other pancreatic cancer cell lines. Ectopic TINCR expression reduced the viability of PANC-1 cells primarily by inducing apoptosis, as evidenced by increased Bax and decreased Bcl-2 expression. Overexpression of TINCR significantly increased the percentage of apoptotic cells. It also decreased the migration and invasion ability of PANC-1 cells, as demonstrated in wound healing and transwell assays. In addition, overexpression of TINCR-suppressed proteins is associated with the Wnt/β-catenin signaling pathway in PANC-1 cells. In the xenograft mouse model, overexpression of TINCR inhibited tumor growth, EMT markers, and proteins associated with the Wnt/β-catenin pathway. This study sheds light on the tumour-suppressive role of TINCR in PANC-1 cells and suggests its potential as a therapeutic target. These results shed light on the molecular mechanisms underlying the impact of TINCR on pancreatic cancer and offer promising opportunities for innovative therapeutic strategies to improve outcomes in this serious malignancy.
PubDate: Sat, 30 Mar 2024 00:00:00 GMT
- Azithromycin-loaded liposomal hydrogel: a step forward for enhanced
treatment of MRSA-related skin infections
Abstract: Azithromycin (AZT) encapsulated into various types of liposomes (AZT-liposomes) displayed pronounced in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) (1). The present study represents a follow-up to this previous work, attempting to further explore the anti-MRSA potential of AZT-liposomes when incorporated into chitosan hydrogel (CHG). Incorporation of AZT-liposomes into CHG (liposomal CHGs) was intended to ensure proper viscosity and texture properties of the formulation, modification of antibiotic release, and enhanced antibacterial activity, aiming to upgrade the therapeutical potential of AZT-liposomes in localized treatment of MRSA-related skin infections. Four different liposomal CHGs were evaluated and compared on the grounds of antibacterial activity against MRSA, AZT release profiles, cytotoxicity, as well as texture, and rheological properties. To our knowledge, this study is the first to investigate the potential of liposomal CHGs for the topical localized treatment of MRSA-related skin infections. CHG ensured proper viscoelastic and texture properties to achieve prolonged retention and prolonged release of AZT at the application site, which resulted in a boosted anti-MRSA effect of the entrapped AZT-liposomes. With respect to anti-MRSA activity and biocompatibility, formulation CATL-CHG (cationic liposomes in CHG) is considered to be the most promising formulation for the treatment of MRSA-related skin infections.
PubDate: Tue, 26 Dec 2023 00:00:00 GMT
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