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Pharmaceutical Research
Journal Prestige (SJR): 1.077
Citation Impact (citeScore): 3
Number of Followers: 182  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1573-904X - ISSN (Online) 0724-8741
Published by Springer-Verlag Homepage  [2570 journals]
  • Functional Albumin Nanoformulations to Fight Adrenocortical Carcinoma: a
           Redox-Responsive Approach
    • Abstract: Purpose Solid tumors exhibit an altered redox state in comparison with normal tissues due to tumor hypoxia, lower pH, and elevated levels of the tripeptide glutathione. This study describes the preparation of functional redox-responsive nanoparticles proposed as delivery vehicle of Doxorubicin in adrenocortical cancer in vitro. Methods Curcumin and Lipoic acid were conjugated to Human Serum Albumin and nanoparticle systems were prepared via a modified desolvation method. Scanning electron microscopy, Fourier transmission IR, dynamic light scattering and differential scanning calorimetry analyses were used to characterize the nanoparticles. Balb3T3 and H295R were used as in vitro models of health and cancer cells, respectively. Results Nanoparticles with a spherical shape and a mean diameter of 70 nm were observed, increasing up to ten-folds upon exposure to glutathione 10 mM. Redox responsive Doxorubicin release was recorded, with loaded nanoparticles significantly enhancing the drug cytotoxicity against H295R adrenocortical tumor cells. Cell uptake experiments revealed a rapid and efficient internalization of the nanoparticles. Conclusions A valuable tools to actively improve the in vitro anticancer activity of Doxorubicin against adrenocortical cancer was proposed. The effectiveness of the delivery vehicle is related to the presence of both Lipoic acid and Curcumin moieties, enhancing the glutathione responsivity, and the drug cytotoxicity, respectively.
      PubDate: 2020-02-14
  • A Proposed Treatment Approach to Treat Lethal Mutating Cancers
    • Abstract: Abstract A proposed treatment using dual-peptide ligand masks, that are functional extensions to existing analogous mammalian immune system structures, to bind to cancer cell surface proteins and stop mutating cancers that could evade presently used engineered immune cell therapies. One treatment injects the dual-peptide ligand masks into the blood stream of patients, and another treatment injects the dual-peptide ligand masks into localized cancers to bind to cancer cell surface proteins. The mammalian immune system has long used analogous, but more complex structures called pentraxins to physically link various types of pathogens to immune cells for neutralization. This treatment approach offers potential advantages in increased binding adaptability to mutations in the surface proteins of cancer cells, and potentially lower treatment cost compared to engineered immune cell treatments against cancer, especially against mutating cancer cells, even compared to extremely specific and costly monoclonal antibody treatments or engineered T cell treatments.
      PubDate: 2020-02-13
  • Tumescent Injections in Subcutaneous Pig Tissue Disperse Fluids
           Volumetrically and Maintain Elevated Local Concentrations of Additives for
           Several Hours, Suggesting a Treatment for Drug Resistant Wounds
    • Abstract: Purpose Bolus injection of fluid into subcutaneous tissue results in accumulation of fluid at the injection site. The fluid does not form a pool. Rather, the injection pressure forces the interstitial matrix to expand to accommodate the excess fluid in its volume, and the fluid becomes bound similar to that in a hydrogel. We seek to understand the properties and dynamics of externally tumesced (swollen) subcutaneous tissue as a first step in assessing whether tumescent antibiotic injections into wounds may provide a novel method of treatment. Methods Subcutaneous injections of saline are performed in live and dead pigs and the physical properties (volume, expansion ratio, residence time, apparent diffusion constant) of the resulting fluid deposits are observed with diffusion-weighted magnetic resonance imaging, computed tomography, and 3D scanning. Results Subcutaneous tissue can expand to a few times its initial volume to accommodate the injected fluid, which is dispersed thoroughly throughout the tumescent volume. The fluid spreads to peripheral unexpanded regions over the course of a few minutes, after which it remains in place for several hours. Eventually the circulation absorbs the excess fluid and the tissue returns to its original state. Conclusions Given the evidence for dense fluid dispersal and several-hour residence time, a procedure is proposed whereby tumescent antibiotic injections are used to treat drug-resistant skin infections and chronic wounds that extend into the subcutaneous tissue. The procedure has the potential to effectively treat otherwise untreatable wounds by keeping drug concentrations above minimum inhibitory levels for extended lengths of time.
      PubDate: 2020-02-10
  • Regulation of Lipid Membrane Partitioning of Tamoxifen by Ionic Strength
           and Cholesterol
    • Abstract: Purpose The purpose of this study was to inspect the interactions between an anti-breast cancer, TAM, with model of lipid membranes composed of either zwitterionic DPPC LUVs or anionic DPPG LUVs and how they depend on ionic strength and cholesterol. Methods The Kp of TAM into DPPC and DPPG LUVs were determined at three different NaCl concentrations by second derivative UV-Vis spectrophotometry. The effect of cholesterol incorporated into these LUVs on TAM’s Kp was also assessed. The ATR-FTIR measurements were carried out to verify structural changes within the acyl chain and head group regions of the liposomes upon TAM partitioning. Results Increasing salt concentration produced negligible impact on the partitioning of TAM into DPPC bilayer as its Kp remained unaffected whilst induced outstanding reduction of TAM’s Kp into DPPG liposomes. Furthermore, TAM was found to disorder the lipids’ acyl chains, which could result in an increase in the membrane fluidity, a necessary piece of information to refer to when prescribing TAM dosage for administration. Additionally, cholesterol showed astoundingly opposite contribution to the partitioning of TAM into the LUVs, as its Kp value reduced in DPPC/Chol bilayer yet increased in DPPG/Chol liposomes. Conclusion Ionic strength and cholesterol play a noteworthy role in regulation of TAM partitioning into lipid membranes as they could obstruct or promote such action.
      PubDate: 2020-02-10
  • Sensitivity of Different In Vitro Performance Tests and Their In Vivo
           Relevance for Calcipotriol/Betamethasone Ointment
    • Abstract: Purpose We compared results of in vitro performance testing with results of therapeutic equivalence study for calcipotriol/betamethasone ointment, to evaluate their sensitivity and in vivo relevance. Methods Different in vitro methods were used to evaluate drug release and permeation from the test and reference ointment. Moreover, 444 psoriasis patients were randomized in the therapeutic equivalence study and the parameters of efficacy and safety were compared with in vitro results. Results In vitro release and permeation rate of calcipotriol and betamethasone from the test formulation was higher than from the reference product for all methods used (p ≤ 0.05 for calcipotriol and p < 0.01 for betamethasone). Observed batch-to-batch variability of reference product confirmed high sensitivity and discriminatory power of in vitro methods. Higher release and permeation rate of calcipotriol and betamethasone from test product was reflected in the efficacy assessment (mean response difference 4.78 mPASI percentage points), but the observed difference was within the equivalence margins. Systemic exposure to calcipotriol and betamethasone was similar in both treatment groups. Conclusion The results of in vitro experiments rank orderly correlated with the results of clinical study. In vitro methods are more sensitive and highly discriminatory when compared to in vivo performance.
      PubDate: 2020-02-10
  • Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid
           Nanoparticles for Processability and Sustained Release
    • Abstract: Aims Crosslinked hyaluronic acid (X-linked HA) is not suitable for making microneedles because of the low fluidity of X-linked HA hydrogel. Microneedles were fabricated using X-linked HA nanoparticles (X-linked HA-NPs) to utilize the sustained drug delivery capability of X-linked HA-NPs and to obtain the processability advantages of X-linked HA. Method The puncture performance of a microneedle array patch (MAP) made of crosslinked hyaluronic acid nanoparticles (X-linked HA-NP-MAP) was evaluated by insertion in vitro into porcine skin. After a predetermined attachment time, the remaining height of the X-linked HA-NP-MAP was measured to determine the dissolution rate. X-linked HA-NP-MAP and free HA-MAP containing Rhodamine B isothiocyanate-dextran were administered into the back skin of mice, and the relative fluorescent intensity in the back skin was measured over time. Results The puncture performance of the X-linked HA-NP-MAP was over 90%. The diameter of redispersed X-linked HA-NPs was same as that of the premolded X-linked HA-NPs. The dissolution rate was not different from that of free HA-MAP. In an in vivo experiment, X-linked HA-NP-MAP was administered into the mouse’s back skin successfully and the relative fluorescent intensity of X-linked HA-NP-MAP lasted longer than that of HA-MAP. Conclusion X-linked HA-NPs provide the biocompatibility, the processability of micromolding, sustained drug release, successful penetration into the skin, and relatively short insertion time for full disintegration of NPs in the skin. X-linked HA-NP-MAP can be used for various applications that require several days of sustained drug release.
      PubDate: 2020-02-07
  • Effect of Controlled Heat Application on Topical Diclofenac Formulations
           Evaluated by In Vitro Permeation Tests (IVPT) Using Porcine and Human Skin
    • Abstract: Purpose Heat therapy is widely used for pain relief and may unintentionally be used in conjunction with pain relieving topical formulations. The purpose of this study was to evaluate the influence of heat on the permeation of diclofenac through porcine and human skin, comparing four marketed products. Methods In vitro permeation tests (IVPT) were performed on porcine skin from a single miniature pig and human skin from three donors. Skin temperature was maintained at either 32 ± 1°C or 42 ± 1°C to mimic normal and elevated skin temperature conditions, respectively. Results IVPT studies on porcine and human skin were able to demonstrate heat-induced enhancement in flux and cumulative amount of drug permeated from the four diclofenac products. The pivotal data showed the most significant heat-induced enhancement for the solution, followed by the patch and two gels in decreasing order of significance based on p values. Diclofenac solution showed the highest flux and cumulative amount permeated at both baseline and elevated skin temperature compared to the patch and gels. Conclusions The studies demonstrated that exposure to heat can alter drug permeation from topical formulations, but the increased levels are not expected to lead to systemic concentrations that are of concern. Formulation design and excipients can influence drug permeation at elevated skin temperature.
      PubDate: 2020-02-07
  • Neuroprotective Effect of New Nanochelating-Based Nano Complex, ALZc3,
           Against Aβ (1–42) -Induced Toxicity in Rat: a Comparison with Memantine
    • Abstract: Purpose The current drugs for Alzheimer’s disease (AD) are only used to slow or delay the progression of the pathology. So using a novel technology is a necessity to synthesize more effective medications to control this most common cause of dementia. In this study, using nanochelating technology, ALZc3 was synthesized and its therapeutic effects were evaluated in comparison with memantine on a well-known rat model of AD, which is based on Amyloid-βeta (Aβ) injection into the brain. Materials and Methods Aβ (1–42) was injected bilaterally into the CA1 area of the hippocampus of male rats and then animals were treated daily by oral administration of Alz-C3, memantine or their vehicles. Activities of antioxidant enzymes catalase and superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels, as well as Bax/Bcl-2 ratio, caspase-3 activation, and TNF-α expression were evaluated 7 days after Aβ injection. Finally, learning and memory of the rats were assessed by Morris water maze test. Results ALZc3 and memantine improved memory impairment and antioxidant activity and reduced TNF-α expression, caspase-3 activity and Bax/Bcl-2 ratio in the rat’s hippocampus. The results showed a superiority of ALZC3 compared to memantine in reducing caspase-3, increasing CAT activity in Aβ (1–42)-injected groups and improving apoptosis factor in healthy mice. Conclusion These results indicated that ALZc3 could significantly prevent the memory impairment and Aβ (1–42) toxicity. Thus, ALZc3 could be a promising novel anti-AD agent.
      PubDate: 2020-02-04
  • Quantifying In Vivo Luminal Drug Solubilization
           -Supersaturation-Precipitation Profiles to Explain the Performance of
           Lipid Based Formulations
    • Abstract: Purpose To evaluate the role of supersaturation in the in vivo absorption of fenofibrate (FFB), after oral administration in a medium-chain lipid-based formulation (MCLBF). Methods FFB was loaded at 90% and 20% w/w of saturated solubility in MCLBF. The two formulations were pre-dispersed in purified water at 5% w/w (ME90% and 20%, respectively) and orally administered to rats to measure in vivo luminal drug concentrations. Results FFB precipitated in the stomach due to lipid digestion by gastric lipases and loss of solubilization capacity. This was most significant for ME90%. For ME90%, a high degree of supersaturation was also observed in the duodenum, however, precipitated FFB crystals rapidly re-dissolved. The combination of supersaturation and rapid re-dissolution appeared to drive effective absorption in the upper intestine. For ME20%, FFB precipitated in the stomach but not in the crystalline form and rapidly re-dissolved. Supersaturation in the duodenum again appeared to be the major driver of oral absorption. Conclusions The data provide one of the first studies of in vivo luminal drug concentration, supersaturation and absorption from lipid based formulations and suggests that for FFB, whilst very high supersaturation may drive in vitro and in vivo precipitation, re-dissolution and drug absorption is rapid and efficient.
      PubDate: 2020-02-03
  • Photo-Degradation of Therapeutic Proteins: Mechanistic Aspects
    • Abstract: Abstract Purpose: Therapeutic proteins are sensitive to photo-degradation by UV A and visible light. As none of the essential amino acids exhibits significant absorption in the UV A and visible light regions, the underlying mechanisms of photo-degradation induced by UV A and visible light are not well understood. This review addresses potential mechanisms, by which protein structure, oxidative modifications or impurities can promote the photo-degradation of therapeutic proteins during the exposure to UV A and visible light.
      PubDate: 2020-02-03
  • Enabling Combinatorial siRNA Delivery against Apoptosis-Related Proteins
           with Linoleic Acid and α-Linoleic Acid Substituted Low Molecular Weight
    • Abstract: Purpose Short interfering RNA (siRNA) therapy promises a new era in treatment of breast cancers but effective delivery systems are needed for clinical use. Since silencing complementary targets may offer improved efficacy, this study was undertaken to identify non-viral carriers for combinatorial siRNA delivery for more effective therapy. Methods A library of lipid-substituted polymers from low molecular weight polyethyleneimine (PEI), linoleic acid (LA) and α-linoleic acid (αLA) with amide or thioester linkages was prepared and investigated for delivering Mcl-1, survivin and STAT5A siRNAs in breast cancer cells. Results The effective polymers formed 80–190 nm particles with similar zeta-potentials, but the serum stability was greater for complexes formed with amide-linked lipid conjugates. The LA and αLA substitutions, with the low molecular weight PEI (1.2 kDa and 2.0 kDa) were able to deliver siRNA effectively to cells and retarded the growth of breast cancer cells. The amide-linked lipid substituents showed higher cellular delivery of siRNA as compared to thioester linkages. Upon combinational delivery of siRNAs, growth of MCF-7 cells was inhibited to a greater extent with 2.0PEI-LA9 mediated delivery of Mcl-1 combined survivin siRNAs as compared to individual siRNAs. The qRT-PCR analysis confirmed the decrease in mRNA levels of target genes with specific siRNAs and 2.0PEI-LA9 was the most effective polymer for delivering siRNAs (either single or in combination). Conclusions This study yielded effective siRNA carriers for combinational delivery of siRNAs. Careful choice of siRNA combinations will be critical since targeting individual genes might alter the expression of other critical mediators.
      PubDate: 2020-02-03
  • Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3
           and AOX1 in Women with Preterm Labor
    • Abstract: Purpose This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. Methods Plasma samples were collected at 1.5, 4, and 10 h after first oral administration of sulindac. Plasma concentrations of sulindac and its active metabolite (sulindac sulfide) were determined, and pharmacokinetic analysis was performed with NONMEM 7.3. Results The mean maternal and gestational ages at the time of dosing were 32.5 ± 4.4 (range, 20–41) years and 27.4 ± 4.4 (range, 16.4–33.4) weeks, respectively. In the population pharmacokinetic analysis, one depot compartment model of sulindac with absorption lag time best described the data. The metabolism of sulindac and sulindac sulfide was described using Michaelis-Menten kinetics. In stepwise modeling, gestational age impacted volume of distribution (Vc), and FMO3 rs2266782 was shown by the Michaelis constant to affect conversion of sulindac sulfide to sulindac (KM32); these were retained in the final model. Conclusions Genetic polymorphisms of FMO3 and AOX1 could affect the pharmacokinetics of sulindac in women who undergo preterm labor. The results of this study could help clinicians develop individualized treatment plans for administering sulindac.
      PubDate: 2020-01-28
  • Pyrvinium Pamoate Use in a B cell Acute Lymphoblastic Leukemia Model of
           the Bone Tumor Microenvironment
    • Abstract: Purpose Pyrvinium pamoate (PP) is an anthelmintic drug that has been found to have anti-cancer activity in several cancer types. In the present study, we evaluated PP for potential anti-leukemic activity in B cell acute lymphoblastic leukemia (ALL) cell lines, in an effort to evaluate the repurposing potential of this drug in leukemia. Methods ALL cells were treated with PP at various concentrations to determine its effect on cell proliferation. Metabolic function was tested by evaluating Extracellular Acidification Rate (ECAR) and Oxygen Consumption Rate (OCR). Lastly, 3D spheroids were grown, and PP was reformulated into nanoparticles to evaluate distribution effectiveness. Results PP was found to inhibit ALL proliferation, with varied selectivity to different ALL cell subtypes. We also found that PP’s cell death activity was specific for leukemic cells, as primary normal immune cells were resistant to PP-mediated cell death. Metabolic studies indicated that PP, in part, inhibits mitochondrial oxidative phosphorylation. To increase the targeting of PP to a hypoxic bone tumor microenvironment (BTME) niche, we successfully encapsulated PP in a nanoparticle drug delivery system and demonstrated that it retained its anti-leukemic activity in a hemosphere assay. Conclusion We have demonstrated that PP is a novel therapeutic lead compound that counteracts the respiratory reprogramming found in refractory ALL cells and can be effectively formulated into a nanoparticle delivery system to target the BTME.
      PubDate: 2020-01-27
  • Measuring pH and Buffer Capacity in Fluids Aspirated from the Fasted Upper
           Gastrointestinal Tract of Healthy Adults
    • Abstract: Purpose The design of biorelevant conditions for in vitro evaluation of orally administered drug products is contingent on obtaining accurate values for physiologically relevant parameters such as pH, buffer capacity and bile salt concentrations in upper gastrointestinal fluids. Methods The impact of sample handling on the measurement of pH and buffer capacity of aspirates from the upper gastrointestinal tract was evaluated, with a focus on centrifugation and freeze-thaw cycling as factors that can influence results. Since bicarbonate is a key buffer system in the fasted state and is used to represent conditions in the upper intestine in vitro, variations on sample handling were also investigated for bicarbonate-based buffers prepared in the laboratory. Results Centrifugation and freezing significantly increase pH and decrease buffer capacity in samples obtained by aspiration from the upper gastrointestinal tract in the fasted state and in bicarbonate buffers prepared in vitro. Comparison of data suggested that the buffer system in the small intestine does not derive exclusively from bicarbonates. Conclusions Measurement of both pH and buffer capacity immediately after aspiration are strongly recommended as “best practice” and should be adopted as the standard procedure for measuring pH and buffer capacity in aspirates from the gastrointestinal tract. Only data obtained in this way provide a valid basis for setting the physiological parameters in physiologically based pharmacokinetic models.
      PubDate: 2020-01-27
  • Correction to: Population Pharmacokinetics, Efficacy Exposure-response
           Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with
           Rheumatoid Arthritis
    • Abstract: The article was published with an incomplete title. The complete title is “Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with Rheumatoid Arthritis” The original article has been corrected.
      PubDate: 2020-01-24
  • Senescence and the Impact on Biodistribution of Different Nanosystems: the
           Discrepancy on Tissue Deposition of Graphene Quantum Dots,
           Polycaprolactone Nanoparticle and Magnetic Mesoporous Silica Nanoparticles
           in Young and Elder Animals
    • Abstract: Purposes Senescence is an inevitable and irreversible process, which may lead to loss in muscle and bone density, decline in brain volume and loss in renal clearance. Although aging is a well-known process, few studies on the consumption of nanodrugs by elderly people were performed. Methods We evaluated three different nanosystems: i) carbon based nanosystem (Graphene Quantum Dots, GQD), ii) polymeric nanoparticles and mesoporous silica (magnetic core mesoporous silica, MMSN). In previous studies, our group has already characterized GQD and MMSN nanoparticles by dynamic light scattering analysis, atomic force microscopy, transmission electron microscopy, X-ray diffraction, Raman analysis, fluorescence and absorbance. The polymeric nanoparticle has been characterized by AFM and DLS. All the nanosystems were radiolabeled with 99 m-Tc by. The in vivo biodistribution/tissue deposition analysis evaluation was done using elder (PN270) and young (PN90) mice injected with radioactive nanosystems. Results The nanosystems used in this study were well-formed as the radiolabeling processes were stable. Biodistribution analysis showed that there is a decrease in the uptake of the nanoparticles in elder mice when compared to young mice, showing that is necessary to increase the initial dose in elder people to achieve the same concentration when compared to young animals. Conclusion The discrepancy on tissue distribution of nanosystems between young and elder individuals must be monitored, as the therapeutic effect will be different in the groups. Noteworthy, this data is an alarm that some specific conditions must be evaluated before commercialization of nano-drugs. Graphical Changes between younger and elderly individuals are undoubtedly, especially in drug tissue deposition, biodistribution and pharmacokinetics. The same thought should be applied to nanoparticles. A comprehensive analysis on how age discrepancy change the biological behavior of nanoparticles has been performed.
      PubDate: 2020-01-22
  • Correction to: Comparative Assessment of the New PDE7 Inhibitor –
           GRMS-55 and Lisofylline in Animal Models of Immune-Related Disorders: A
           PK/PD Modeling Approach
    • Abstract: There was a mistake in the unit of clearance (Cl) in Table II. In addition, the descriptions of V1(ROL) and V1(GRMS-55) were imprecise and the reference number in the footnote below this table should be (9). The corrected Table appears below.
      PubDate: 2020-01-21
  • Dual-Targeted Delivery of Nanoparticles Encapsulating Paclitaxel and
           Everolimus: a Novel Strategy to Overcome Breast Cancer Receptor
    • Abstract: Purpose The intratumoral heterogeneity observed in breast cancer (BC), in particular with regard to cell surface receptor expression, can hinder the success of many targeted cancer therapies. The development of novel therapeutic agents that target more than one receptor can overcome this inherent property of tumors and can facilitate their selective internalization in cancer cells. The goal of this study is to develop a drug combination-loaded nanoparticle (NP) formulation that is actively-targeted to HER2 and EGFR receptors on BC cells. Methods A polymeric NP formulation was prepared which co-encapsulated a synergistic combination of the chemotherapeutic agent, paclitaxel (PTX), and the mTOR inhibitor, everolimus (EVER), and is targeted to HER2 and EGFR receptors on BC cells using antibody Fab fragments as the targeting moieties. The physicochemical characteristics of the dual-targeted formulation (Dual-NP) were evaluated, along with its cytotoxic profile (in both, monolayer and 3D BC models), as well as the degree of cellular uptake in HER2high/EGFRmod and HER2neg/EGFRlow BC cells. Results Dual-NPs were found to have significantly higher cytotoxicity relative to HER2 mono-targeted (T-NPs) and untargeted NPs (UT-NPs) in HER2high/EGFRmod monolayer BC cells after 72 h exposure, while no significant difference was observed in HER2neg/EGFRlow cells. However, in the HER2high/EGFRmod spheroids, the cytotoxicity of Dual-NPs was comparable to that of T-NPs. This was thought to be attributed to the previously reported downregulation of EGFR in 3D in comparison to 2D BC models. Dual-NPs had significantly higher cellular uptake relative to UT-NPs and T-NPs in HER2high/EGFRmod BC cells after 24 h exposure, whereas in the HER2neg/EGFRlow cells, the increase in cellular uptake of the Dual-NPs was not as high as the level achieved in the HER2high/EGFRmod cells. Blocking HER2 and EGFR significantly reduced the uptake of T-NPs and Dual-NPs in the HER2high/EGFRmod BC cells, demonstrating specific binding to both EGFR and HER2. Conclusions The dual-targeting strategy developed in this study in conjunction with a potentially promising delivery vector for a synergistic combination therapy can overcome receptor heterogeneity, yielding significant improvements in the cytotoxicity and cellular uptake in BC cells.
      PubDate: 2020-01-21
  • Medication Tracking: Design and Fabrication of a Dry Powder Inhaler with
           Integrated Acoustic Element by 3D Printing
    • Abstract: Purpose Asthma is a prevalent lung disorder that cause heavy burdens globally. Inhalation medicaments can relieve symptoms, improve lung function and, thus, the quality of life. However, it is well-documented that patients often do not get the prescribed dose out of an inhaler and the deposition of drug is suboptimal, due to incorrect handling of the device and wrong inhalation technique. This study aims to design and fabricate an acoustic dry powder inhaler (ADPI) for monitoring inhalation flow and related drug administration in order to evaluate whether the patient receives the complete dose out of the inhaler. Methods The devices were fabricated using 3D printing and the impact of the acoustic element geometry and printing resolution on the acoustic signal was investigated. Commercial Foradil (formoterol fumarate) capsules were used to validate the availability of the ADPI for medication dose tracking. The acoustic signal was analysed with Partial-Least-Squares (PLS) regression. Results Indicate that specific acoustic signals could be generated at different air flow rates using a passive acoustic element with specific design features. This acoustic signal could be correlated with the PLS model to the air flow rate. A more distinct sound spectra could be acquired at higher printing resolution. The sound spectra from the ADPI with no capsule, a full capsule and an empty capsule are different which could be used for medication tracking. Conclusions This study shows that it is possible to evaluate the medication quality of inhaled medicaments by monitoring the acoustic signal generated during the inhalation process.
      PubDate: 2020-01-21
  • Design and Characterization of Injectable Poly(Lactic-Co-Glycolic Acid)
           Pastes for Sustained and Local Drug Release
    • Abstract: Purpose We describe the preparation of injectable polymeric paste (IPP) formulations for local and sustained release of drugs. Furthermore, we include the characterization and possible applications of such pastes. Particular attention is paid to characteristics relevant to the successful clinical formulation development, such as viscosity, injectability, degradation, drug release, sterilization, stability performance and pharmacokinetics. Methods Paste injectability was characterized using measured viscosity and the Hagen-Poiseuille equation to determine injection forces. Drug degradation, release and formulation stability experiments were performed in vitro and drug levels were quantified using HPLC-UV methods. Pharmacokinetic evaluation of sustained-release lidocaine IPPs used five groups of six rats receiving increasing doses subcutaneously. An anti-cancer formulation was evaluated in a subcutaneous tumor xenograft mouse model. Results The viscosity and injectability of IPPs could be controlled by changing the polymeric composition. IPPs demonstrated good long-term stability and tunable drug-release with low systemic exposure in vivo in rats. Preliminary data in a subcutaneous tumor model points to a sustained anticancer effect. Conclusions These IPPs are tunable platforms for local and sustained delivery of drugs and have potential for further clinical development to treat a number of diseases.
      PubDate: 2020-01-21
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