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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted by number of followers
Nature Reviews Drug Discovery     Full-text available via subscription   (Followers: 332)
International Journal of Drug Policy     Hybrid Journal   (Followers: 254)
Journal of Clinical Oncology     Hybrid Journal   (Followers: 242)
Journal of Medicinal Chemistry     Hybrid Journal   (Followers: 157)
Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 155)
Drugs     Full-text available via subscription   (Followers: 146)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 98)
Pharmaceutical Research     Hybrid Journal   (Followers: 94)
European Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 86)
Drug Safety     Full-text available via subscription   (Followers: 83)
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 56)
Biomaterials     Hybrid Journal   (Followers: 54)
Clinical Pharmacology & Therapeutics     Hybrid Journal   (Followers: 44)
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 42)
Journal of Controlled Release     Hybrid Journal   (Followers: 38)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 38)
International Journal of Pharmaceutics     Hybrid Journal   (Followers: 37)
Clinical Therapeutics     Hybrid Journal   (Followers: 34)
European Journal of Pharmaceutics and Biopharmaceutics     Hybrid Journal   (Followers: 34)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 33)
British Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 32)
Journal of Pharmacy and Pharmacology     Full-text available via subscription   (Followers: 31)
Drug Development and Industrial Pharmacy     Hybrid Journal   (Followers: 29)
PharmacoEconomics     Full-text available via subscription   (Followers: 27)
Clinical Pharmacokinetics     Full-text available via subscription   (Followers: 27)
AAPS Journal     Hybrid Journal   (Followers: 26)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 25)
Journal of Clinical Psychopharmacology     Hybrid Journal   (Followers: 24)
International Journal of Pharmacy Practice     Full-text available via subscription   (Followers: 24)
Toxicology and Applied Pharmacology     Hybrid Journal   (Followers: 24)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
Journal of Pharmacokinetics and Pharmacodynamics     Hybrid Journal   (Followers: 22)
Journal of Pain & Palliative Care Pharmacotherapy     Hybrid Journal   (Followers: 21)
Trends in Pharmacological Sciences     Full-text available via subscription   (Followers: 20)
Journal of Applied Toxicology     Hybrid Journal   (Followers: 19)
Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 19)
Pharmaceutical Development and Technology     Hybrid Journal   (Followers: 19)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 19)
Clinical Trials     Hybrid Journal   (Followers: 18)
Toxicology     Hybrid Journal   (Followers: 18)
Journal of Pharmaceutical and Biomedical Analysis     Hybrid Journal   (Followers: 18)
Clinical Toxicology     Hybrid Journal   (Followers: 18)
International Journal of Toxicology     Hybrid Journal   (Followers: 17)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 16)
Journal of Clinical Pharmacy and Therapeutics     Hybrid Journal   (Followers: 16)
Journal of Natural Products     Hybrid Journal   (Followers: 16)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 15)
Toxicology Letters     Hybrid Journal   (Followers: 15)
Journal of Pharmacy Practice     Hybrid Journal   (Followers: 15)
Psychopharmacology     Hybrid Journal   (Followers: 15)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 14)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 14)
European Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 14)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 13)
American Journal of Therapeutics     Hybrid Journal   (Followers: 13)
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 13)
Journal of the American Pharmacists Association     Full-text available via subscription   (Followers: 13)
Clinical Research and Regulatory Affairs     Hybrid Journal   (Followers: 12)
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 12)
Current Pharmaceutical Design     Hybrid Journal   (Followers: 12)
Journal of Oncology Pharmacy Practice     Hybrid Journal   (Followers: 12)
Journal of Psychopharmacology     Hybrid Journal   (Followers: 11)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 11)
Toxicology in Vitro     Hybrid Journal   (Followers: 11)
Drug Development Research     Hybrid Journal   (Followers: 11)
Drug Metabolism and Disposition     Hybrid Journal   (Followers: 11)
Seminars in Oncology Nursing     Full-text available via subscription   (Followers: 10)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Journal of Separation Science     Hybrid Journal   (Followers: 10)
CNS Drugs     Full-text available via subscription   (Followers: 10)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 10)
Journal of Medical Marketing     Hybrid Journal   (Followers: 10)
Drugs & Aging     Full-text available via subscription   (Followers: 10)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 9)
Food Additives & Contaminants Part A     Hybrid Journal   (Followers: 9)
Journal of Pharmacology and Experimental Therapeutics     Hybrid Journal   (Followers: 9)
Environmental Toxicology and Pharmacology     Hybrid Journal   (Followers: 9)
Medicinal Chemistry     Hybrid Journal   (Followers: 9)
Biometrical Journal     Hybrid Journal   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 9)
Prescriber     Hybrid Journal   (Followers: 9)
ChemMedChem     Hybrid Journal   (Followers: 9)
Current Opinion in Pharmacology     Hybrid Journal   (Followers: 9)
European Journal of Pharmacology     Hybrid Journal   (Followers: 8)
Inhalation Toxicology     Hybrid Journal   (Followers: 8)
Antiviral Research     Hybrid Journal   (Followers: 8)
Drug Metabolism Reviews     Hybrid Journal   (Followers: 8)
Progress in Neuro-Psychopharmacology and Biological Psychiatry     Hybrid Journal   (Followers: 8)
Human & Experimental Toxicology     Hybrid Journal   (Followers: 8)
Drug Delivery     Open Access   (Followers: 8)
BioDrugs     Full-text available via subscription   (Followers: 8)
Frontiers in Drug Design & Discovery     Hybrid Journal   (Followers: 8)
Expert Review of Pharmacoeconomics & Outcomes Research     Full-text available via subscription   (Followers: 8)
Experimental and Clinical Psychopharmacology     Full-text available via subscription   (Followers: 7)
Toxicology Mechanisms and Methods     Hybrid Journal   (Followers: 7)
Journal of Pharmacological and Toxicological Methods     Hybrid Journal   (Followers: 7)
Clinical and Experimental Pharmacology and Physiology     Hybrid Journal   (Followers: 7)
Scandinavian Journal of Clinical and Laboratory Investigation     Hybrid Journal   (Followers: 7)
Epilepsy Research     Hybrid Journal   (Followers: 7)
Clinical Drug Investigation     Full-text available via subscription   (Followers: 7)
Journal of Veterinary Pharmacology and Therapeutics     Hybrid Journal   (Followers: 6)
Toxicology and Industrial Health     Hybrid Journal   (Followers: 6)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 6)
Journal of Cardiovascular Pharmacology     Hybrid Journal   (Followers: 6)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Current Drug Discovery Technologies     Hybrid Journal   (Followers: 6)
Current Drug Delivery     Hybrid Journal   (Followers: 6)
Current Therapeutic Research     Open Access   (Followers: 6)
Expert Review of Cardiovascular Therapy     Full-text available via subscription   (Followers: 6)
Neuropharmacology     Hybrid Journal   (Followers: 5)
Current Drug Metabolism     Hybrid Journal   (Followers: 5)
Fitoterapia     Hybrid Journal   (Followers: 5)
Expert Review of Molecular Diagnostics     Full-text available via subscription   (Followers: 5)
Expert Review of Anti-infective Therapy     Full-text available via subscription   (Followers: 5)
Anti-Infective Agents     Hybrid Journal   (Followers: 5)
Toxicon     Hybrid Journal   (Followers: 5)
Medicinal Research Reviews     Hybrid Journal   (Followers: 5)
Investigational New Drugs     Hybrid Journal   (Followers: 5)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 5)
Current Cancer Therapy Reviews     Hybrid Journal   (Followers: 5)
Reviews of Physiology, Biochemistry and Pharmacology     Hybrid Journal   (Followers: 4)
Planta Medica     Hybrid Journal   (Followers: 4)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 4)
Pharmaceutical Medicine     Full-text available via subscription   (Followers: 4)
Journal of Child and Adolescent Psychopharmacology     Hybrid Journal   (Followers: 4)
CNS Drug Reviews     Open Access   (Followers: 4)
Inpharma Weekly     Full-text available via subscription   (Followers: 4)
Journal of Labelled Compounds and Radiopharmaceuticals     Hybrid Journal   (Followers: 4)
Immunopharmacology and Immunotoxicology     Hybrid Journal   (Followers: 4)
International Journal of Pharmaceutical and Healthcare Marketing     Hybrid Journal   (Followers: 4)
Inflammation Research     Hybrid Journal   (Followers: 4)
Cancer Chemotherapy and Pharmacology     Hybrid Journal   (Followers: 4)
International Journal of Neuropsychopharmacology     Open Access   (Followers: 3)
Pharmacology & Therapeutics     Hybrid Journal   (Followers: 3)
Physiology International     Full-text available via subscription   (Followers: 3)
Cardiovascular Therapeutics     Open Access   (Followers: 3)
ASSAY and Drug Development Technologies     Hybrid Journal   (Followers: 3)
Pharmacopsychiatry     Hybrid Journal   (Followers: 3)
Chemotherapy     Full-text available via subscription   (Followers: 3)
Therapeutic Drug Monitoring     Hybrid Journal   (Followers: 3)
Current Drug Therapy     Hybrid Journal   (Followers: 3)
Research in Social and Administrative Pharmacy     Hybrid Journal   (Followers: 3)
PharmacoEconomics & Outcomes News     Full-text available via subscription   (Followers: 3)
Journal of Aerosol Medicine and Pulmonary Drug Delivery     Hybrid Journal   (Followers: 3)
Journal of Ethnopharmacology     Hybrid Journal   (Followers: 3)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
Journal of Pain Management & Medicine     Open Access   (Followers: 3)
Journal of Infection and Chemotherapy     Hybrid Journal   (Followers: 3)
Journal of Cardiovascular Pharmacology and Therapeutics     Hybrid Journal   (Followers: 3)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Acta Pharmacologica Sinica     Hybrid Journal   (Followers: 3)
Microbial Drug Resistance     Hybrid Journal   (Followers: 3)
Frontiers in Medicinal Chemistry     Hybrid Journal   (Followers: 3)
Human Psychopharmacology Clinical and Experimental     Hybrid Journal   (Followers: 3)
BMC Pharmacology     Open Access   (Followers: 2)
The Brown University Psychopharmacology Update     Hybrid Journal   (Followers: 2)
International Clinical Psychopharmacology     Hybrid Journal   (Followers: 2)
Canadian Journal of Physiology and Pharmacology     Hybrid Journal   (Followers: 2)
Journal of Drug Targeting     Hybrid Journal   (Followers: 2)
Inflammopharmacology     Hybrid Journal   (Followers: 2)
Journal of Inflammation     Open Access   (Followers: 2)
Fundamental & Clinical Pharmacology     Hybrid Journal   (Followers: 2)
Behavioural Pharmacology     Hybrid Journal   (Followers: 2)
Vascular Pharmacology     Hybrid Journal   (Followers: 2)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Biomedicine & Pharmacotherapy     Full-text available via subscription   (Followers: 2)
Clinical Neuropharmacology     Hybrid Journal   (Followers: 2)
Drugs in R & D     Full-text available via subscription   (Followers: 2)
International Immunopharmacology     Hybrid Journal   (Followers: 2)
Pharmacology Biochemistry and Behavior     Hybrid Journal   (Followers: 2)
Letters in Drug Design & Discovery     Hybrid Journal   (Followers: 2)
Archiv der Pharmazie     Hybrid Journal   (Followers: 2)
Pharmacological Reviews     Hybrid Journal   (Followers: 2)
Molecular Pharmacology     Hybrid Journal   (Followers: 2)
Journal of Microencapsulation: Microcapsules, Liposomes, Nanoparticles, Microcells, Microspheres     Hybrid Journal   (Followers: 2)
Toxicological & Environmental Chemistry     Hybrid Journal   (Followers: 2)
Particulate Science and Technology: An International Journal     Hybrid Journal   (Followers: 1)
Pharmacological Research     Hybrid Journal   (Followers: 1)
Current Enzyme Inhibition     Hybrid Journal   (Followers: 1)
Journal of Neuroimmune Pharmacology     Hybrid Journal   (Followers: 1)
Current Pharmaceutical Analysis     Hybrid Journal   (Followers: 1)
Current Neuropharmacology     Hybrid Journal   (Followers: 1)
Pharmacogenetics and Genomics     Hybrid Journal   (Followers: 1)
Journal of Texture Studies     Hybrid Journal   (Followers: 1)
Pharmaceutical Biology     Open Access  
Journal of Liposome Research     Hybrid Journal  
Toxin Reviews     Hybrid Journal  
Kaohsiung Journal of Medical Sciences     Open Access  
Redox Report     Open Access  
Pharmacology     Full-text available via subscription  
Pharmaceutical Chemistry Journal     Hybrid Journal  
NeuroMolecular Medicine     Hybrid Journal  
Journal of Ocular Pharmacology and Therapeutics     Hybrid Journal  
Harm Reduction Journal     Open Access  
Current Nanoscience     Hybrid Journal  
Infectious Disorders - Drug Targets     Hybrid Journal  
Current Bioactive Compounds     Hybrid Journal  
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal  
Autonomic & Autacoid Pharmacology     Hybrid Journal  

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Similar Journals
Journal Cover
Pharmaceutical Research
Journal Prestige (SJR): 1.077
Citation Impact (citeScore): 3
Number of Followers: 94  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1573-904X - ISSN (Online) 0724-8741
Published by Springer-Verlag Homepage  [2467 journals]
  • Analytical Workflows to Unlock Predictive Power in Biotherapeutic
           Developability

    • Free pre-print version: Loading...

      Abstract: Purpose Forming accurate data models that assist the design of developability assays is one area that requires a deep and practical understanding of the problem domain. We aim to incorporate expert knowledge into the model building process by creating new metrics from instrument data and by guiding the choice of input parameters and Machine Learning (ML) techniques. Methods We generated datasets from the biophysical characterisation of 5 monoclonal antibodies (mAbs). We explored combinations of techniques and parameters to uncover the ones that better describe specific molecular liabilities, such as conformational and colloidal instability. We also employed ML algorithms to predict metrics from the dataset. Results We found that the combination of Differential Scanning Calorimetry (DSC) and Light Scattering thermal ramps enabled us to identify domain-specific aggregation in mAbs that would be otherwise overlooked by common developability workflows. We also found that the response to different salt concentrations provided information about colloidal stability in agreement with charge distribution models. Finally, we predicted DSC transition temperatures from the dataset, and used the order of importance of different metrics to increase the explainability of the model. Conclusions The new analytical workflows enabled a better description of molecular behaviour and uncovered links between structural properties and molecular liabilities. In the future this new understanding will be coupled with ML algorithms to unlock their predictive power during developability assessment.
      PubDate: 2022-12-05
       
  • Quantifying Agglomerate-to-Wall Impaction in Dry Powder Inhalers

    • Free pre-print version: Loading...

      Abstract: Purpose The probability of agglomerate-to-wall collision was quantified using a unique image processing technique applied to high-speed microscopic images. The study aimed to investigate the effects of flow rate and particle size on the percentage of colliding agglomerates detected within an in-house powder dispersion device. Method The device consists of a swirl chamber and two tangential inlets in various configurations, designed to emulate the geometric features of commercial devices such as the Aerolizer® and Osmohaler®. The test cases were conducted with constant flow rates of 30 SLPM and 60 SLPM. Four powder samples were tested, including carrier Respitose® SV010 (median volume diameter 104 µm, span 1.7) and mannitol of three constituent primary particle sizes (3 µm, 5 µm and 7 µm; span 1.6 – 1.9). Results At the lower flow rate of 30 SLPM, collision frequencies were significantly different between powders of different constituent particle sizes, but the effects of powder properties diminished on increasing the flow rate to 60 SLPM. At the higher flow rate, all powders experienced a significant increase in the proportion of colliding particles. Conclusion Analysis of collision events showed that the probability of collision for each agglomerate increased with agglomerate diameter and velocity. Experimental data of agglomerate-to-wall collision were utilised to develop a logistic regression model that can accurately predict collisions with various powders and flow rates.
      PubDate: 2022-12-05
       
  • Crystal and Particle Engineering – An Indispensable Tool for Developing
           and Manufacturing Quality Pharmaceutical Products

    • Free pre-print version: Loading...

      PubDate: 2022-12-05
       
  • Convolutional Neural Networks Enable Highly Accurate and Automated
           Subvisible Particulate Classification of Biopharmaceuticals

    • Free pre-print version: Loading...

      Abstract: Abstract Quantification of subvisible particles, which are generally defined as those ranging in size from 2 to 100 µm, is important as critical characteristics for biopharmaceutical formulation development. Micro Flow Imaging (MFI) provides quantifiable morphological parameters to study both the size and type of subvisible particles, including proteinaceous particles as well as non-proteinaceous features incl. silicone oil droplets, air bubble droplets, etc., thus enabling quantitative and categorical particle attribute reporting for quality control. However, limitations in routine MFI image analysis can hinder accurate subvisible particle classification. In this work, we custom-built a subvisible particle-aware Convolutional Neural Network, SVNet, which has a very small computational footprint, and achieves comparable performance to prior state-of-art image classification models. SVNet significantly improves upon current standard operating procedures for subvisible particulate assessments as confirmed by thorough real-world validation studies.
      PubDate: 2022-12-05
       
  • Spray Freeze Drying of Biologics: A Review and Applications for Inhalation
           Delivery

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      Abstract: Abstract Biopharmaceuticals have established an indisputable presence in the pharmaceutical pipeline, enabling highly specific new therapies. However, manufacturing, isolating, and delivering these highly complex molecules to patients present multiple challenges, including the short shelf-life of biologically derived products. Administration of biopharmaceuticals through inhalation has been gaining attention as an alternative to overcome the burdens associated with intravenous administration. Although most of the inhaled biopharmaceuticals in clinical trials are being administered through nebulization, dry powder inhalers (DPIs) are considered a viable alternative to liquid solutions due to enhanced stability. While freeze drying (FD) and spray drying (SD) are currently seen as the most viable solutions for drying biopharmaceuticals, spray freeze drying (SFD) has recently started gaining attention as an alternative to these technologies as it enables unique powder properties which favor this family of drug products. The present review focus on the application of SFD to produce dry powders of biopharmaceuticals, with special focus on inhalation delivery. Thus, it provides an overview of the critical quality attributes (CQAs) of these dry powders. Then, a detailed explanation of the SFD fundamental principles as well as the different existing variants is presented, together with a discussion regarding the opportunities and challenges of SFD as an enabling technology for inhalation-based biopharmaceuticals. Finally, a review of the main formulation strategies and their impact on the stability and performance of inhalable biopharmaceuticals produced via SDF is performed. Overall, this review presents a comprehensive assessment of the current and future applications of SFD in biopharmaceuticals for inhalation delivery.
      PubDate: 2022-12-01
       
  • Advanced Solid Formulations For Vulvovaginal Candidiasis

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      Abstract: Vulvovaginal candidiasis (VVC) is an opportunistic and endogenous infection caused by a fungus of the Candida genus, which can cause pruritus, dysuria, vulvar edema, fissures and maceration of the vulva. The treatment of vaginal candidiasis is carried out mainly by antifungal agents of azole and polyene classes; however, fungal resistance cases have been often observed. For this reason, new therapeutic agents such as essential oils, probiotics and antimicrobial peptides are being investigated, which can be combined with conventional drugs. Local administration of antimicrobials has also been considered to allow greater control of drug delivery and reduce or avoid undesirable systemic adverse effects. Conventional dosage forms such as creams and ointments result in reduced residence time in the mucosa and non-sustained and variable drug delivery. Therefore, advanced solid formulations such as intravaginal rings, vaginal films, sponges and nanofibers have been purposed. In these systems, polymers in different ratios are combined aiming to achieve a specific drug release profile and high mucoadhesion. Overall, a more porous matrix structure leads to a higher rate of drug release and mucoadhesion. The advantages, limitations and technological aspects of each dosage form are discussed in detail in this review. Graphical
      PubDate: 2022-11-30
       
  • What Do We Know About the Smallpox Virus' A Journey Between Clinic and
           Therapy

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      Abstract: Purpose Modern research is increasingly focusing on the study of new viruses and the re-emergence of past microbes, such as Coronaviruses, particularly Sars-Cov2 that was responsible for the very recent pandemic. Methods and Results This infection manifested itself and still continues to manifest as a severe respiratory syndrome. The main discriminator of whether or not one succeeds in overcoming this infection may depend on a great many factors, but the main one is definitely determined by vaccination, which has minimized hospitalizations and more severe syndromes. Conclusion Recently, a new virus, the monkeypox virus, which was previously confined to Central and West Africa but is now gradually spreading to more than 30 countries including the United States of America, where such an infection is not endemic, is coming forward again.
      PubDate: 2022-11-30
       
  • Lipid Microparticles Show Similar Efficacy With Lipid Nanoparticles in
           Delivering mRNA and Preventing Cancer

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      Abstract: Purpose Messenger RNA (mRNA) has shown great promise for vaccine against both infectious diseases and cancer. However, mRNA is unstable and requires a delivery vehicle for efficient cellular uptake and degradation protection. So far, lipid nanoparticles (LNPs) represent the most advanced delivery platform for mRNA delivery. However, no published studies have compared lipid microparticles (LMPs) with lipid nanoparticles (LNPs) in delivering mRNA systematically, therefore, we compared the impact of particle size on delivery efficacy of mRNA vaccine and subsequent immune responses. Methods Herein, we prepared 3 different size lipid particles, from nano-sized to micro-sized, and they loaded similar amounts of mRNA. These lipid particles were investigated both in vitro and in vivo, followed by evaluating the impact of particle size on inducing cellular and humoral immune responses. Results In this study, all mRNA vaccines showed a robust immune response and lipid microparticles (LMPs) show similar efficacy with lipid nanoparticles (LNPs) in delivering mRNA and preventing cancer. In addition, immune adjuvants, either toll like receptors or active molecules from traditional Chinese medicine, can improve the efficacy of mRNA vaccines. Conclusions Considering the efficiency of delivery and endocytosis, besides lipid nanoparticles with size smaller than 150 nm, lipid microparticles (LMPs) also have the potential to be an alternative and promising delivery system for mRNA vaccines.
      PubDate: 2022-11-30
       
  • Optimization of Lung Surfactant Coating of siRNA Polyplexes for Pulmonary
           Delivery

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      Abstract: Purpose The aim of this study was to understand how coating with a pulmonary surfactant, namely Alveofact, affects the physicochemical parameters as well as in vitro behavior of polyethylenimine (PEI) polyplexes for pulmonary siRNA delivery. Methods Alveofact-coated polyplexes were prepared at different Alveofact:PEI coating ratios and analyzed in terms of size, PDI and zeta potential as well as morphology by transmission electron microscopy. The biological behavior was evaluated in a lung epithelial cell line regarding cell viability, cellular uptake via flow cytometry and gene downregulation by qRT-PCR. Furthermore, a 3D ALI culture model was established to test the mucus diffusion and cellular uptake by confocal microscopy as well as gene silencing activity by qRT-PCR. Results After optimizing the coating process by testing different Alveofact:PEI coating ratios, a formulation with suitable parameters for lung delivery was obtained. In lung epithelial cells, Alveofact-coated polyplexes were well tolerated and internalized. Furthermore, the coating improved the siRNA-mediated gene silencing efficiency. Alveofact-coated polyplexes were then tested on a 3D air-liquid interface (ALI) culture model that, by expressing tight junctions and secreting mucus, resembles important traits of the lung epithelium. Here, we identified the optimal Alveofact:PEI coating ratio to achieve diffusion through the mucus layer while retaining gene silencing activity. Interestingly, the latter underlined the importance of establishing appropriate in vitro models to achieve more consistent results that better predict the in vivo activity. Conclusion The addition of a coating with pulmonary surfactant to polymeric cationic polyplexes represents a valuable formulation strategy to improve local delivery of siRNA to the lungs. Graphical
      PubDate: 2022-11-29
       
  • In vitro Dissolution Testing of Rifampicin Powder Formulations For
           

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      Abstract: Purpose The purpose of this study was to evaluate the in vitro lung dissolution of amorphous and crystalline powder formulations of rifampicin in polyethylene oxide (PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), and to predict the in vivo plasma concentration–time profiles using the in vitro data. Methods The in vitro dissolution and permeation profiles of respirable rifampicin particles were studied using a custom-made dissolution apparatus. Data from the in vitro dissolution test were used to estimate the parameters to be used as the input for the simulation of in vivo plasma concentration–time profiles using STELLA® software. For prediction of in vivo profiles, a one-compartment model either with a first order elimination or with a Michaelis–Menten kinetics-based elimination was used. Results Compared to the crystalline formulation, the amorphous formulation showed rapid in vitro dissolution suggesting their possible faster in vivo absorption and higher plasma concentrations of rifampicin following lung delivery. However, the simulations suggested that both powder formulations would result in similar plasma-concentration time profiles of rifampicin. Conclusions Use of an in vitro dissolution test coupled with a simulation model for prediction of plasma-concentration time profiles of an inhaled drug was demonstrated in this work. These models can also be used in the design of inhaled formulations by controlling their release and dissolution properties to achieve desired lung retention or systemic absorption following delivery to the lungs.
      PubDate: 2022-11-29
       
  • Preclinical Considerations for Long-acting Delivery of Tenofovir
           Alafenamide from Subdermal Implants for HIV Pre-exposure Prophylaxis

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      Abstract: Purpose Long-acting formulations of the potent antiretroviral prodrug tenofovir alafenamide (TAF) hold potential as biomedical HIV prevention modalities. Here, we present a rigorous comparison of three animal models, C57BL/6 J mice, beagle dogs, and merino sheep for evaluating TAF implant pharmacokinetics (PKs). Methods Implants delivering TAF over a wide range of controlled release rates were tested in vitro and in mice and dogs. Our existing PK model, supported by an intravenous (IV) dosing dog study, was adapted to analyze mechanistic aspects underlying implant TAF delivery. Results TAF in vitro release in the 0.13 to 9.8 mg d−1 range with zero order kinetics were attained. Implants with equivalent fabrication parameters released TAF in mice and sheep at rates that were not statistically different, but were 3 times higher in dogs. When two implants were placed in the same subcutaneous pocket, a two-week creep to Cmax was observed in dogs for systemic drug and metabolite concentrations, but not in mice. Co-modeling IV and TAF implant PK data in dogs led to an apparent TAF bioavailability of 9.6 in the single implant groups (compared to the IV group), but only 1.5 when two implants were placed in the same subcutaneous pocket. Conclusions Based on the current results, we recommend using mice and sheep, with macaques as a complementary species, for preclinical TAF implant evaluation with the caveat that our observations may be specific to the implant technology used here. Our report provides fundamental, translatable insights into multispecies TAF delivery via long-acting implants.
      PubDate: 2022-11-23
       
  • Assessing Antigen-Adjuvant Complex Stability Against Physical Stresses By
           wNMR

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      Abstract: Abstract This study applies an emerging analytical technology, wNMR (water proton nuclear magnetic resonance), to assess the stability of aluminum adjuvants and antigen-adjuvant complexes against physical stresses, including gravitation, flow and freeze/thaw. Results from wNMR are verified by conventional analytical technologies, including static light scattering and microfluidic imaging. The results show that wNMR can quickly and noninvasively determine whether an aluminum adjuvant or antigen-adjuvant complex sample has been altered by physical stresses.
      PubDate: 2022-11-22
       
  • Challenges and Strategies to Enhance the Systemic Absorption of Inhaled
           Peptides and Proteins

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      Abstract: Abstract Proteins and peptides-based therapeutics are making substantial access to the market due to their obvious advantages of strong potency, high specificity and desirable safety profile. However, most clinical products are mainly delivered via parenteral route with inferior convenience. Lung is an attractive non-invasive alternative passage for systemic administration of biologics with numerous outstanding features, as examples of large absorptive surface area, extensive vascularization and mild local microenvironment. Even so, mucociliary clearance, alveolar macrophage phagocytosis, enzymatic metabolism, pulmonary surfactant adsorption and limited epithelium permeability constitute major obstacles affecting the systemic absorption of inhaled proteins and peptides. This article begins by giving a brief overview of challenges for the systemic absorption of inhaled proteins and peptides, and then goes on to a comprehensive review of possible strategies for enhanced pulmonary absorption, including chemical modification, addition of protease inhibitors, incorporation of absorption enhancers, modification with fusion proteins and development of particulate-based drug delivery systems. These strategies can provide enhanced transmembrane absorption capacity while avoiding pulmonary clearance, offering a valuable reference for designing pulmonary delivery systems of protein and peptide drugs.
      PubDate: 2022-11-16
       
  • CNS Delivery of Nucleic Acid Therapeutics: Beyond the Blood–Brain
           Barrier and Towards Specific Cellular Targeting

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      Abstract: Nucleic acid-based therapeutic molecules including small interfering RNA (siRNA), microRNA(miRNA), antisense oligonucleotides (ASOs), messenger RNA (mRNA), and DNA-based gene therapy have tremendous potential for treating diseases in the central nervous system (CNS). However, achieving clinically meaningful delivery to the brain and particularly to target cells and sub-cellular compartments is typically very challenging. Mediating cell-specific delivery in the CNS would be a crucial advance that mitigates off-target effects and toxicities. In this review, we describe these challenges and provide contemporary evidence of advances in cellular and sub-cellular delivery using a variety of delivery mechanisms and alternative routes of administration, including the nose-to-brain approach. Strategies to achieve subcellular localization, endosomal escape, cytosolic bioavailability, and nuclear transfer are also discussed. Ultimately, there are still many challenges to translating these experimental strategies into effective and clinically viable approaches for treating patients. Graphical
      PubDate: 2022-11-15
       
  • Random Heteropolymer Excipients Improve the Colloidal Stability of a
           Monoclonal Antibody for Subcutaneous Administration

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      Abstract: Purpose Developing stable high concentration monoclonal antibody (mAb) formulations is increasingly important to move toward subcutaneous (SC) administration for better patient experience. Challenges stemming from protein–protein interactions in these crowded solutions, such as colloidal instability, limit the feasibility of some formulations because of concerns of safety, product quality, and/or manufacturability. Herein, we report novel random heteropolymer excipients that improve the colloidal stability of a high concentration mAb formulation for SC administration. Methods A library of polymers was synthesized and screened by a high-throughput, absorbance-based assay. The lead polymers were selected and characterized for their ability to alter the precipitation kinetics of a mAb in physiologically relevant conditions using two model systems. Results Biophysical testing via surface tension measurements, isothermal titration calorimetry (ITC), microscale thermophoresis (MST), and intrinsic fluorescence quenching indicated that the polymers delayed onset of mAb precipitation from a combination of surfactant behaviour and interactions with the protein to prevent protein–protein interactions leading to colloidal instability. Conclusions The random heteropolymers described are a new class of excipients that may enable development of SC mAb formulations previously inaccessible to patients.
      PubDate: 2022-11-15
       
  • Bone-Targeted Dual Functional Lipid-coated Drug Delivery System for
           Osteosarcoma Therapy

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      Abstract: Purpose or Objective Osteosarcoma is well-known for its high incidence in children and adolescents and long-term bone pain, which seriously reduces the life quality of patients. Cisplatin (CDDP), as the first-line anti-osteosarcoma drug, has been used in many anticancer treatments. At the same time, the serious side effects of platinum (Pt) drugs have also attracted widespread attention. To accurately deliver Pt drugs to the lesion site and realize controlled release of Pt drugs, certain modified delivery systems have been extensively studied. Methods Among them, liposomes have been approved for clinical cancer treatment due to their highly biocompatibility and superior modifiability. Here, we developed a bone-targeted dual functional lipid-coated drug delivery system, lipid-coated CDDP alendronate nanoparticles (LCA NPs) to target the bone and precisely deliver the drugs to the tumor site. Cell toxicity, apoptosis and cellular uptake were detected to evaluate the anticancer effect for LCA NPs. Furthermore, transwell assay and wound healing assay were conducted to estimate the osteosarcoma cell migration and invasion. Hemolysis assay was utilized to assess the biocapitibility of the kind of NPs. Results With the aim of bone-targeted unit alendronate (ALD), LCA NPs serve as a rich bone homing Pt delivery system to exert efficient anticancer effects and synergistically reduce bone resorption and bone loss potentially. Conclusions By providing a highly biocompatible platform for osteosarcoma therapy, LCA NPs may help to significantly enhance the anticancer effect of Pt and greatly reduce the systemic toxicity and side effects of Pt towards osteosarcoma.
      PubDate: 2022-11-15
       
  • Development of a Workflow to Engineer Tailored Microparticles Via Inkjet
           Printing

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      Abstract: Purpose New drug development and delivery approaches result in an ever-increasing demand for tailored microparticles with defined sizes and structures. Inkjet printing technologies could be promising new processes to engineer particles with defined characteristics, as they are created to precisely deliver liquid droplets with high uniformity. Methods D-mannitol was used as a model compound alone or co-processed with the pore former agent ammonium bicarbonate, and the polymer polyethylene glycol 200. Firstly, a drop shape analyzer was used to characterize and understand ink/substrate interactions, evaporation, and solidification kinetics. Consequently, the process was transferred to a laboratory-scale inkjet printer and the resulting particles collected, characterized and compared to others obtained via an industrial standard technique. Results The droplet shape analysis allowed to understand how 3D structures are formed and helped define the formulation and process parameters for inkjet printing. By adjusting the drop number and process waveform, spherical particles with a mean size of approximately 100 µm were obtained. The addition of pore former and polymer allowed to tailor the crystallization kinetics, resulting in particles with a different surface (i.e., spike-like surface) and bulk (e.g. porous and non-porous) structure. Conclusion The workflow described enabled the production of 3D structures via inkjet printing, demonstrating that this technique can be a promising approach to engineer microparticles.
      PubDate: 2022-11-15
       
  • Synthesis and Pharmacological Evaluation of Novel Triazole-Pyrimidine
           Hybrids as Potential Neuroprotective and Anti-neuroinflammatory Agents

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      Abstract: Objective Neuroprotection is a precise target for the treatment of neurodegenerative diseases, ischemic stroke, and traumatic brain injury. Pyrimidine and its derivatives have been proven to use antiviral, anticancer, antioxidant, and antimicrobial activity prompting us to study the neuroprotection and anti-inflammatory activity of the triazole-pyrimidine hybrid on human microglia and neuronal cell model. Methods A series of novel triazole-pyrimidine-based compounds were designed, synthesized and characterized by mass spectra, 1HNMR, 13CNMR, and a single X-Ray diffraction analysis. Further, the neuroprotective, anti-neuroinflammatory activity was evaluated by cell viability assay (MTT), Elisa, qRT-PCR, western blotting, and molecular docking. Results The molecular results revealed that triazole-pyrimidine hybrid compounds have promising neuroprotective and anti-inflammatory properties. Among the 14 synthesized compounds, ZA3-ZA5, ZB2-ZB6, and intermediate S5 showed significant anti-neuroinflammatory properties through inhibition of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production in LPS-stimulated human microglia cells. From 14 compounds, six (ZA2 to ZA6 and intermediate S5) exhibited promising neuroprotective activity by reduced expression of the endoplasmic reticulum (ER) chaperone, BIP, and apoptosis marker cleaved caspase-3 in human neuronal cells. Also, a molecular docking study showed that lead compounds have favorable interaction with active residues of ATF4 and NF-kB proteins. Conclusion The possible mechanism of action was observed through the inhibition of ER stress, apoptosis, and the NF-kB inflammatory pathway. Thus, our study strongly indicates that the novel scaffolds of triazole-pyrimidine-based compounds can potentially be developed as neuroprotective and anti-neuroinflammatory agents. Graphical
      PubDate: 2022-11-14
       
  • TPGS Decorated Liposomes as Multifunctional Nano-Delivery Systems

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      Abstract: Abstract Liposomes are sphere-shaped vesicles that can capture therapeutics either in the outer phospholipid bilayer or inner aqueous core. Liposomes, especially when surface-modified with functional materials, have been used to achieve many benefits in drug delivery, including improving drug solubility, oral bioavailability, pharmacokinetics, and delivery to disease target sites such as cancers. Among the functional materials used to modify the surface of liposomes, the FDA-approved non-ionic surfactant D-alpha-tocopheryl polyethylene glycol succinate (TPGS) is increasingly being applied due to its biocompatibility, lack of toxicity, applicability to various administration routes and ability to enhance solubilization, stability, penetration and overall pharmacokinetics. TPGS decorated liposomes are emerging as a promising drug delivery system for various diseases and are expected to enter the market in the coming years. In this review article, we focus on the multifunctional properties of TPGS-coated liposomes and their beneficial therapeutic applications, including for oral drug delivery, vaccine delivery, ocular administration, and the treatment of various cancers. We also suggest future directions to optimise the manufacture and performance of TPGS liposomes and, thus, the delivery and effect of encapsulated diagnostics and therapeutics.
      PubDate: 2022-11-14
       
  • Nanotechnology-Based Nucleic Acid Vaccines for Treatment of Ovarian Cancer

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      Abstract: Anticancer vaccines represent a promising approach for effective treatment of cancer and along with recent advantages of nucleic acid-based vaccines for other diseases form a prospective and potentially efficacious direction of the research, development and clinical applications. Despite the ongoing several clinical trials of mRNA vaccines for the treatment of various types of cancer, to-date no cancer vaccines were approved by the US Food and Drug Administration. The present review analyzes and summarizes major approaches for treating of different forms of ovarian cancer including mRNA-based vaccines as well as nanotechnology-based approaches for their delivery. Graphical
      PubDate: 2022-11-14
       
 
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