8,753 results match your criteria Pharmaceutical research[Journal]


The Controlled Release and Anti-Inflammatory Activity of a Tetramethylpyrazine-Loaded Thermosensitive Poloxamer Hydrogel.

Pharm Res 2019 Feb 19;36(4):52. Epub 2019 Feb 19.

Zhaoke (Hefei) Pharmaceutical Co. Ltd., Hefei, 230088, People's Republic of China.

Purpose: Tetramethylpyrazine-loaded poloxamer hydrogel materials were studied to achieve the controlled release of tetramethylpyrazine.

Methods: First, hydrogels having different concentrations of poloxamer 407 and poloxamer 188 were prepared. The gelling temperature and viscosity were measured. Read More

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http://dx.doi.org/10.1007/s11095-019-2580-0DOI Listing
February 2019

Impact of a Heat Shock Protein Impurity on the Immunogenicity of Biotherapeutic Monoclonal Antibodies.

Pharm Res 2019 Feb 15;36(4):51. Epub 2019 Feb 15.

School of Biological Sciences, Faculty of Biology Medicine and Health Manchester Academic Health Science Centre, The University of Manchester, Michael Smith Building Oxford Road, Manchester, M13 9PT, UK.

Purpose: Anti-drug antibodies can impair the efficacy of therapeutic proteins and, in some circumstances, induce adverse health effects. Immunogenicity can be promoted by aggregation; here we examined the ability of recombinant mouse heat shock protein 70 (rmHSP70) - a common host cell impurity - to modulate the immune responses to aggregates of two therapeutic mAbs in mice.

Methods: Heat and shaking stress methods were used to generate aggregates in the sub-micron size range from two human mAbs, and immunogenicity assessed by intraperitoneal exposure in BALB/c mice. Read More

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http://dx.doi.org/10.1007/s11095-019-2586-7DOI Listing
February 2019

Evaluation of the Immunomodulatory Effects of All-Trans Retinoic Acid Solid Lipid Nanoparticles and Human Mesenchymal Stem Cells in an A549 Epithelial Cell Line Model.

Pharm Res 2019 Feb 13;36(4):50. Epub 2019 Feb 13.

School of Pharmacy, Royal College of Surgeons in Ireland, Ardilaun House Block B, 111 St Stephen's Green, Dublin 2, Ireland.

Purpose: To investigate two potential strategies aimed at targeting the inflammatory pathogenesis of COPD: a small molecule, all trans retinoic acid (atRA) and human mesenchymal stem cells (hMSCs).

Methods: atRA was formulated into solid lipid nanoparticles (SLNs) via the emulsification-ultrasonication method, and these SLNs were characterised physicochemically. Assessment of the immunomodulatory effects of atRA-SLNs on A549 cells in vitro was determined using ELISA. Read More

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http://dx.doi.org/10.1007/s11095-019-2583-xDOI Listing
February 2019
3 Reads

Elucidating the Mechanism of Absorption of Fast-Acting Insulin Aspart: The Role of Niacinamide.

Pharm Res 2019 Feb 11;36(3):49. Epub 2019 Feb 11.

Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark.

Purpose: Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart containing two additional excipients: niacinamide, to increase early absorption, and L-arginine, to optimize stability. The aim of this study was to evaluate the impact of niacinamide on insulin aspart absorption and to investigate the mechanism of action underlying the accelerated absorption.

Methods: The impact of niacinamide was assessed in pharmacokinetic analyses in pigs and humans, small angle X-ray scattering experiments, trans-endothelial transport assays, vascular tension measurements, and subcutaneous blood flow imaging. Read More

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http://dx.doi.org/10.1007/s11095-019-2578-7DOI Listing
February 2019
1 Read

Analyzing the Mechanisms Behind Macrolide Antibiotic-Induced Liver Injury Using Quantitative Systems Toxicology Modeling.

Pharm Res 2019 Feb 7;36(3):48. Epub 2019 Feb 7.

DILIsym Services, Inc., a Simulations Plus Company, 6 Davis Drive, PO Box 12317, Research Triangle Park, North Carolina, 27709, USA.

Purpose: Macrolide antibiotics are commonly prescribed treatments for drug-resistant bacterial infections; however, many macrolides have been shown to cause liver enzyme elevations and one macrolide, telithromycin, has been pulled from the market by its provider due to liver toxicity. This work seeks to assess the mechanisms responsible for the toxicity of macrolide antibiotics.

Methods: Five macrolides were assessed in in vitro systems designed to test for bile acid transporter inhibition, mitochondrial dysfunction, and oxidative stress. Read More

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http://dx.doi.org/10.1007/s11095-019-2582-yDOI Listing
February 2019

The Binding of Human IgG to Minipig FcγRs - Implications for Preclinical Assessment of Therapeutic Antibodies.

Pharm Res 2019 Feb 5;36(3):47. Epub 2019 Feb 5.

Pharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.

Purpose: The Göttingen minipig is a relevant non-rodent species for regulatory toxicological studies. Yet, its use with therapeutic antibodies has been limited by the unknown binding properties of human immunoglobulins (huIgG) to porcine Fc gamma receptors (poFcγR) influencing safety and efficacy readouts. Therefore, knowing IgG-FcγR interactions in the animal model is a prerequisite for the use of minipigs in preclinical safety and efficacy studies with therapeutic antibodies. Read More

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http://dx.doi.org/10.1007/s11095-019-2574-yDOI Listing
February 2019

Pharmacokinetics, Tissue Distribution and Excretion of AgS Quantum Dots in Mice and Rats: the Effects of Injection Dose, Particle Size and Surface Charge.

Pharm Res 2019 Feb 4;36(3):46. Epub 2019 Feb 4.

Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. Box: 14155-6153, Tehran, Iran.

Purpose: We systematically investigated the effects of injection dose, particle size and surface charge on the pharmacokinetics, tissue distribution and excretion of AgS quantum dots (Qds) in rats and mice.

Methods: Three different doses of AgS Qds with similar size and composition were administrated to rats and mice. The effect of size and surface charge was investigated with the injection of three sizes (5, 15 and 25 nm) of AgS Qds possessing similar surface charge, as well as 5 nm Qds with a positive surface charge. Read More

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http://dx.doi.org/10.1007/s11095-019-2571-1DOI Listing
February 2019

Dosage Optimization Based on Population Pharmacokinetic Analysis of Tacrolimus in Chinese Patients with Nephrotic Syndrome.

Pharm Res 2019 Feb 4;36(3):45. Epub 2019 Feb 4.

Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, China.

Purpose: The objective of this study was to merge genetic and non-genetic factors of tacrolimus pharmacokinetics to establish a more stable population pharmacokinetic model for individualized dosage regimen in Chinese nephrotic syndrome patients.

Methods: Nephrotic syndrome patients (>16 years old) treated with tacrolimus were included in the study. The population pharmacokinetic approach was analyzed using NONMEM version 7. Read More

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http://dx.doi.org/10.1007/s11095-019-2579-6DOI Listing
February 2019
1 Read

In vitro Pharmacokinetic Cell Culture System that Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages.

Pharm Res 2019 Feb 1;36(3):44. Epub 2019 Feb 1.

Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, 14203, USA.

Purpose: An in vitro dynamic pharmacokinetic (PK) cell culture system was developed to more precisely simulate physiologic nanoparticle/drug exposure.

Methods: A dynamic PK cell culture system was developed to more closely reflect physiologic nanoparticle/drug concentrations that are changing with time. Macrophages were cultured in standard static and PK cell culture systems with rifampin (RIF; 5 μg/ml) or β-glucan, chitosan coated, poly(lactic-co-glycolic) acid (GLU-CS-PLGA) nanoparticles (RIF equivalent 5 μg/ml) for 6 h. Read More

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http://link.springer.com/10.1007/s11095-019-2576-9
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http://dx.doi.org/10.1007/s11095-019-2576-9DOI Listing
February 2019
4 Reads

Particle Surface Roughness Improves Colloidal Stability of Pressurized Pharmaceutical Suspensions.

Pharm Res 2019 Jan 30;36(3):43. Epub 2019 Jan 30.

Department of Mechanical Engineering, 10-269 Donadeo Innovation Centre for Engineering, University of Alberta, Edmonton, Alberta, T6G 1H9, Canada.

Purpose: The effects of particle size and particle surface roughness on the colloidal stability of pressurized pharmaceutical suspensions were investigated using monodisperse spray-dried particles.

Methods: The colloidal stability of multiple suspensions in the propellant HFA227ea was characterized using a shadowgraphic imaging technique and quantitatively compared using an instability index. Model suspensions of monodisperse spray-dried trehalose particles of narrow distributions (GSD < 1. Read More

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http://dx.doi.org/10.1007/s11095-019-2572-0DOI Listing
January 2019

3D Printing of Pharmaceutical and Medical Applications: a New Era.

Pharm Res 2019 Jan 25;36(3):42. Epub 2019 Jan 25.

University of Greenwich, Faculty of Engineering and Sciences, Chatham Maritime, Kent, ME4 4TB, UK.

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http://dx.doi.org/10.1007/s11095-019-2575-xDOI Listing
January 2019
1 Read

Editorial to Theme Issue on Cell Based Therapeutics.

Pharm Res 2019 Jan 23;36(3):41. Epub 2019 Jan 23.

Consulting On Advanced Biologicals (CAB) Ltd, London, UK.

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http://dx.doi.org/10.1007/s11095-019-2573-zDOI Listing
January 2019
1 Read

Review of Biomarkers in Ocular Matrices: Challenges and Opportunities.

Pharm Res 2019 Jan 23;36(3):40. Epub 2019 Jan 23.

Biological Research, Allergan plc, 2525 Dupont Drive, Irvine, California, 92612, USA.

Biomarkers provide a powerful and dynamic approach to improve our understanding of the mechanisms underlying ocular diseases with applications in diagnosis, disease modulation or for predicting and monitoring of clinical response to treatment. Defined as measurable indicator of normal or pathological processes, biomarker evaluation has been used extensively in drug development within clinical settings to better comprehend effectiveness of treatment in ocular diseases. Biomarkers in the eye have the advantage of access to multiple ocular matrices via minimally invasive methods. Read More

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http://dx.doi.org/10.1007/s11095-019-2569-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344398PMC
January 2019
4 Reads

A Population Dynamic Energy Budget-Based Tumor Growth Inhibition Model for Etoposide Effects on Wistar Rats.

Pharm Res 2019 Jan 11;36(3):38. Epub 2019 Jan 11.

Dipartimento di Ingegneria Industriale e dell'Informazione, Universita degli Studi di Pavia, I-27100, Pavia, Italy.

Purpose: This work aimed to develop a population PK/PD tumor-in-host model able to describe etoposide effects on both tumor cells and host in Walker-256 tumor-bearing rats.

Methods: Etoposide was investigated on thirty-eight Wistar rats randomized in five arms: two groups of tumor-free animals receiving either placebo or etoposide (10 mg/kg bolus for 4 days) and three groups of tumor-bearing animals receiving either placebo or etoposide (5 or 10 mg/kg bolus for 8 or 4 days, respectively). To analyze experimental data, a tumor-in-host growth inhibition (TGI) model, based on the Dynamic Energy Budget (DEB) theory, was developed. Read More

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http://link.springer.com/10.1007/s11095-019-2568-9
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http://dx.doi.org/10.1007/s11095-019-2568-9DOI Listing
January 2019
10 Reads

Knockdown of Orphan Transporter SLC22A18 Impairs Lipid Metabolism and Increases Invasiveness of HepG2 Cells.

Pharm Res 2019 Jan 11;36(3):39. Epub 2019 Jan 11.

Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.

Purpose: The aim of this work is to investigate the roles of solute carrier family 22 member 18 (SLC22A18) in lipid metabolism and in establishing the tumor phenotype of HepG2 cells.

Methods: SLC22A18-knockdown HepG2 cells were established by stable transfection with shRNA. Protein expression levels were measured by quantitative proteomics and Western blot analysis. Read More

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http://link.springer.com/10.1007/s11095-018-2565-4
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http://dx.doi.org/10.1007/s11095-018-2565-4DOI Listing
January 2019
6 Reads

Application of a Quality-By-Design Approach to Optimise Lipid-Polymer Hybrid Nanoparticles Loaded with a Splice-Correction Antisense Oligonucleotide: Maximising Loading and Intracellular Delivery.

Pharm Res 2019 Jan 9;36(3):37. Epub 2019 Jan 9.

Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2,, DK-2100, Copenhagen Ø, Denmark.

Background: Antisense oligonucleotides (ASOs) are promising therapeutics for specific modulation of cellular RNA function. However, ASO efficacy is compromised by inefficient intracellular delivery. Lipid-polymer hybrid nanoparticles (LPNs) are attractive mediators of intracellular ASO delivery due to favorable colloidal stability and sustained release properties. Read More

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http://link.springer.com/10.1007/s11095-018-2566-3
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http://dx.doi.org/10.1007/s11095-018-2566-3DOI Listing
January 2019
8 Reads

Ocular Pharmacokinetics of a Topical Ophthalmic Nanomicellar Solution of Cyclosporine (Cequa®) for Dry Eye Disease.

Pharm Res 2019 Jan 7;36(2):36. Epub 2019 Jan 7.

Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri, 2464 Charlotte Street, Kansas City, MO, 64108, USA.

Cequa®, a unique and first-in-class preservative free cyclosporine-A (CsA) nanomicellar topical formulation was recently approved by US FDA for treatment of dry eye disease or keratoconjuntivitis sicca (KCS). Being highly hydrophobic, CsA is currently available as an oil based emulsion, which has its own shortcomings. Developing an aqueous and clear formulation of CsA is imperative yet a challenging need in the quest for a safe and better drug product. Read More

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http://link.springer.com/10.1007/s11095-018-2556-5
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http://dx.doi.org/10.1007/s11095-018-2556-5DOI Listing
January 2019
9 Reads

Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease.

Pharm Res 2019 Jan 7;36(2):34. Epub 2019 Jan 7.

Department of Ophthalmology and of Pathology and Cell Biology, Columbia University, New York, New York, USA.

Inherited retinal diseases (IRDs) are a group of rare, heterogenous eye disorders caused by gene mutations that result in degeneration of the retina. There are currently limited treatment options for IRDs; however, retinal gene therapy holds great promise for the treatment of different forms of inherited blindness. One such IRD for which gene therapy has shown positive initial results is choroideremia, a rare, X-linked degenerative disorder of the retina and choroid. Read More

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http://link.springer.com/10.1007/s11095-018-2564-5
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http://dx.doi.org/10.1007/s11095-018-2564-5DOI Listing
January 2019
8 Reads

Impact of Older Age on the Exposure of Paclitaxel: a Population Pharmacokinetic Study.

Pharm Res 2019 Jan 7;36(2):33. Epub 2019 Jan 7.

Department of Pharmacy &Pharmacology, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, the Netherlands.

Purpose: Limited available data suggest that older patients are more prone to develop paclitaxel-induced toxicity than their younger peers. It remains unclear whether this is related to age-dependent pharmacokinetics (PK) of paclitaxel. Primary objective of this study was to determine the influence of older age on the PK of paclitaxel. Read More

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http://dx.doi.org/10.1007/s11095-018-2563-6DOI Listing
January 2019
2 Reads

Machine Learning Models for the Prediction of Chemotherapy-Induced Peripheral Neuropathy.

Pharm Res 2019 Jan 7;36(2):35. Epub 2019 Jan 7.

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, 431 Kapoor Hall, Buffalo, New York, 14214, USA.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect of cancer chemotherapy that can be life debilitating and cause extreme pain. The multifactorial and poorly understood mechanisms of toxicity have impeded the identification of novel treatment strategies. Computational models of drug neurotoxicity could be implemented in early drug discovery to screen for high-risk compounds and select safer drug candidates for further development. Read More

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http://dx.doi.org/10.1007/s11095-018-2562-7DOI Listing
January 2019
6 Reads

Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods.

Pharm Res 2019 Jan 2;36(2):32. Epub 2019 Jan 2.

Graduate Institute of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Purpose: Various blood collection methods were developed and used in the pharmacokinetic evaluation of drugs. However, the influence of different blood sampling methods on plasma drug concentrations has not been clarified. In the present study, we aimed to determine whether the plasma concentration of a target drug changes based on the collection site and elucidate the mechanism responsible for this change. Read More

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http://dx.doi.org/10.1007/s11095-018-2550-yDOI Listing
January 2019
1 Read

Correction to: Creation of Straight-Chain Cationic Polysaccharide-Based Bile Salt Sequestrants Made from Euglenoid β-1,3-Glucan as Potential Antidiabetic Agents.

Pharm Res 2019 01 2;36(2):31. Epub 2019 Jan 2.

Technical Research Center, KOBELCO Eco-Solutions Co., Ltd., 1-1-4 Murotani, Kobe, Hyogo, 651-2241, Japan.

The corresponding author (Motonari Shibakami) inadvertently failed to include his ORCID ID: http://orcid.org/0000-0003-4484-2982 In the published article. Read More

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http://dx.doi.org/10.1007/s11095-018-2559-2DOI Listing
January 2019
1 Read

Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein.

Pharm Res 2018 Dec 28;36(2):30. Epub 2018 Dec 28.

Nonclinical Development, Relay Therapeutics, 215 First Street, Cambridge, Massachusetts, USA.

According to the free drug hypothesis only the unbound drug is available to act at physiological sites of action, and as such the importance of plasma protein binding primarily resides in its impact on pharmacokinetics and pharmacodynamics. Of the major plasma proteins, alpha-1-acid glycoprotein (AAG) represents an intriguing one primarily due to the high affinity, low capacity properties of this protein. In addition, there are marked species and age differences in protein expression, homology and drug binding affinity. Read More

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http://dx.doi.org/10.1007/s11095-018-2551-xDOI Listing
December 2018
2 Reads

Pharmaceutical Development of AAV-Based Gene Therapy Products for the Eye.

Pharm Res 2018 Dec 27;36(2):29. Epub 2018 Dec 27.

Pharmaceutical Research and Development, Allergan plc, 2525 Dupont Drive, Irvine, California, 92612-1531, USA.

A resurgence of interest and investment in the field of gene therapy, driven in large part by advances in viral vector technology, has recently culminated in United States Food and Drug Administration approval of the first gene therapy product targeting a disease caused by mutations in a single gene. This product, LUXTURNA™ (voretigene neparvovec-rzyl; Spark Therapeutics, Inc., Philadelphia, PA), delivers a normal copy of the RPE65 gene to retinal cells for the treatment of biallelic RPE65 mutation-associated retinal dystrophy, a blinding disease. Read More

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http://dx.doi.org/10.1007/s11095-018-2554-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308217PMC
December 2018
3 Reads

QSAR Development for Plasma Protein Binding: Influence of the Ionization State.

Pharm Res 2018 Dec 27;36(2):28. Epub 2018 Dec 27.

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via la Masa 19, 20156, Milano, Italy.

Purpose: This study explored several strategies to improve the performance of literature QSAR models for plasma protein binding (PPB), such as a suitable endpoint transformation, a correct representation of chemicals, more consistency in the dataset, and a reliable definition of the applicability domain.

Methods: We retrieved human fraction unbound (Fu) data for 670 compounds from the literature and carefully checked them for consistency. Descriptors were calculated taking account of the ionization state of molecules at physiological pH (7. Read More

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http://dx.doi.org/10.1007/s11095-018-2561-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308215PMC
December 2018
1 Read

Anti-Invasive and Anti-Proliferative Effects of shRNA-Loaded Poly(Lactide-Co-Glycolide) Nanoparticles Following RAN Silencing in MDA-MB231 Breast Cancer Cells.

Pharm Res 2018 Dec 17;36(2):26. Epub 2018 Dec 17.

Institute of Cancer Therapeutics, ICT building, University of Bradford, Richmond Road, Bradford, England, BD7 1DP, UK.

Background: Overexpression of the RAN GTP (RAN) gene has been shown to be linked to metastatic activity of MDA-MB231 human breast cancer cells by increasing Ras/MEK/ERK and PI3K/Akt/mTORC1 signalling. The aim of this study was to investigate the potential of polymeric nanoparticles to deliver two novel shRNA sequences, targeted against the RAN gene, to MDA-MB231 cells grown in culture and to assess their effects in a range of biological assays.

Methods: Biodegradable PLGA nanoparticles, loaded with shRNA-1 and shRNA-4, were fabricated using a double emulsion solvent evaporation technique and characterised for size, zeta potential and polydispersity index before testing on the MDA-MB231 cell line in a range of assays including cell viability, migration, invasion and gene knock down. Read More

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http://link.springer.com/10.1007/s11095-018-2555-6
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http://dx.doi.org/10.1007/s11095-018-2555-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297200PMC
December 2018
7 Reads

High Throughput and Computational Repurposing for Neglected Diseases.

Pharm Res 2018 Dec 17;36(2):27. Epub 2018 Dec 17.

Collaborations Pharmaceuticals Inc., 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina, 27606, USA.

Purpose: Neglected tropical diseases (NTDs) represent are a heterogeneous group of communicable diseases that are found within the poorest populations of the world. There are 23 NTDs that have been prioritized by the World Health Organization, which are endemic in 149 countries and affect more than 1.4 billion people, costing these developing economies billions of dollars annually. Read More

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http://dx.doi.org/10.1007/s11095-018-2558-3DOI Listing
December 2018
1 Read

Glaucoma - Next Generation Therapeutics: Impossible to Possible.

Pharm Res 2018 Dec 13;36(2):25. Epub 2018 Dec 13.

Ophthalmology Research, Novartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, Massachusetts, 02139, USA.

The future of next generation therapeutics for glaucoma is strong. The recent approval of two novel intraocular pressure (IOP)-lowering drugs with distinct mechanisms of action is the first in over 20 years. However, these are still being administered as topical drops. Read More

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http://link.springer.com/10.1007/s11095-018-2557-4
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http://dx.doi.org/10.1007/s11095-018-2557-4DOI Listing
December 2018
9 Reads

Creation of Straight-Chain Cationic Polysaccharide-Based Bile Salt Sequestrants Made from Euglenoid β-1,3-Glucan as Potential Antidiabetic Agents.

Pharm Res 2018 Dec 6;36(1):23. Epub 2018 Dec 6.

Technical Research Center, KOBELCO Eco-Solutions Co., Ltd., 1-1-4 Murotani, Kobe, Hyogo, 651-2241, Japan.

Purpose: Straight-chain polysaccharides have a greater potential of selectively adsorbing hydrophobic bile salts than resin-based bile salt sequesters because of ionic and hydrophobic interactions; hence, they may possess antidiabetic activity. The feasibility of using cationic polysaccharides made from euglenoid β-1,3-glucan (referred to as paramylon) as potential antidiabetic agents was examined by using in vitro and animal experiments.

Methods: Cationic straight-chain polysaccharides were synthesized from euglenoid polysaccharide and glycidyltrimethylammonium chloride. Read More

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http://dx.doi.org/10.1007/s11095-018-2553-8DOI Listing
December 2018
3 Reads

Impact of Tryptophan Oxidation in Complementarity-Determining Regions of Two Monoclonal Antibodies on Structure-Function Characterized by Hydrogen-Deuterium Exchange Mass Spectrometry and Surface Plasmon Resonance.

Pharm Res 2018 Dec 10;36(1):24. Epub 2018 Dec 10.

Biologics Development, Bristol-Myers Squibb, 311 Pennington Rocky Hill Road, Pennington, NJ, 08534, USA.

Purpose: Tryptophan's (Trp) unique hydrophobic and structural properties make it an important antigen binding motif when positioned in complementarity-determining regions (CDRs) of monoclonal antibodies (mAbs). Oxidation of Trp residues within the CDR can deleteriously impact antigen binding, particularly if the CDR conformation is altered. The goal of this study was to evaluate the conformational and functional impact of Trp oxidation for two mAb subtypes, which is essential in determining the structure-function relationship and establishing appropriate analytical control strategies during protein therapeutics development. Read More

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http://dx.doi.org/10.1007/s11095-018-2545-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290686PMC
December 2018
1 Read

Aspherical and Spherical InvA497-Functionalized Nanocarriers for Intracellular Delivery of Anti-Infective Agents.

Pharm Res 2018 Dec 5;36(1):22. Epub 2018 Dec 5.

Department Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), 66123, Saarbrücken, Germany.

Purpose: The objective of this work was to evaluate the potential of polymeric spherical and aspherical invasive nanocarriers, loaded with antibiotic, to access and treat intracellular bacterial infections.

Methods: Aspherical nanocarriers were prepared by stretching of spherical precursors, and both aspherical and spherical nanocarriers were surface-functionalized with the invasive protein InvA497. The relative uptake of nanocarriers into HEp-2 epithelial cells was then assessed. Read More

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http://link.springer.com/10.1007/s11095-018-2521-3
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http://dx.doi.org/10.1007/s11095-018-2521-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290668PMC
December 2018
14 Reads

Spray Dried Smectite Clay Particles as a Novel Treatment against Obesity.

Pharm Res 2018 Dec 5;36(1):21. Epub 2018 Dec 5.

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, 5001, Australia.

Purpose: To explore the feasibility of spray dried smectite clay particles fabricated from montmorillonite or laponite materials for adsorbing dietary lipids and reducing rodent weight gain in vivo.

Methods: Spray dried montmorillonite (SD-MMT) and spray dried laponite (SD-LAP) particles were prepared via spray drying. Particle morphology, surface area and redispersion/aggregation properties in aqueous media were characterized. Read More

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http://link.springer.com/10.1007/s11095-018-2552-9
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http://dx.doi.org/10.1007/s11095-018-2552-9DOI Listing
December 2018
19 Reads

HPMA-PLGA Based Nanoparticles for Effective In Vitro Delivery of Rifampicin.

Pharm Res 2018 Dec 3;36(1):19. Epub 2018 Dec 3.

Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India.

Purpose: Tuberculosis (TB) chemotherapy witnesses some major challenges such as poor water-solubility and bioavailability of drugs that frequently delay the treatment. In the present study, an attempt to enhance the aqueous solubility of rifampicin (RMP) was made via co-polymeric nanoparticles approach. HPMA (N-2-hydroxypropylmethacrylamide)-PLGA based polymeric nanoparticulate system were prepared and evaluated against Mycobacterium tuberculosis (MTB) for sustained release and bioavailability of RMP to achieve better delivery. Read More

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http://link.springer.com/10.1007/s11095-018-2543-x
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http://dx.doi.org/10.1007/s11095-018-2543-xDOI Listing
December 2018
10 Reads

Quantitative Structure-Property Relationship for pH-Triggered Drug Release Performance of Acid-Responsive Four/Six-Arms Star Polymeric Micelles.

Pharm Res 2018 Dec 3;36(1):20. Epub 2018 Dec 3.

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510000, People's Republic of China.

Purpose: The pH-responsive copolymer micelles are widely used as carriers in drug delivery system, but there are few micro-level mechanistically explorations on the pH-triggered drug release. Here we elucidate the relationship between drug release behavior of four/six-arms star copolymer micelles and the copolymer structures.

Method: The net cumulative drug release percentage (E) was taken as the dependent variables, block unit autocorrelation descriptors as independent variables. Read More

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http://dx.doi.org/10.1007/s11095-018-2549-4DOI Listing
December 2018
1 Read
3.420 Impact Factor

Different Efflux Transporter Affinity and Metabolism of Tc-2-Methoxyisobutylisonitrile and Tc-Tetrofosmin for Multidrug Resistance Monitoring in Cancer.

Pharm Res 2018 Nov 29;36(1):18. Epub 2018 Nov 29.

School of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.

Background: Little is known about the affinity and stability of Tc-labeled 2-methoxyisobutylisonitrile (Tc-MIBI) and tetrofosmin (Tc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of Tc-labeled compounds for these transporters and their stability.

Methods: Tc-MIBI and Tc-TF were incubated in vesicles expressing P-glycoprotein (MDR1), multidrug resistance-associated protein (MRP)1-4, or breast cancer resistance protein with and without verapamil (MDR1 inhibitor) or MK-571 (MRP inhibitor). Read More

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http://dx.doi.org/10.1007/s11095-018-2548-5DOI Listing
November 2018
2 Reads
3.420 Impact Factor

Alzheimer's Disease Phenotype or Inflammatory Insult Does Not Alter Function of L-Type Amino Acid Transporter 1 in Mouse Blood-Brain Barrier and Primary Astrocytes.

Pharm Res 2018 Nov 28;36(1):17. Epub 2018 Nov 28.

School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.

Purpose: The study aim was to evaluate the effect of Alzheimer's disease (AD) and inflammatory insult on the function of L-type amino acid transporter 1 (Lat1) at the mouse blood-brain barrier (BBB) as well as Lat1 function and expression in mouse primary astrocytes.

Methods: The Lat1 function and expression was determined in wildtype astrocytes with and without lipopolysaccharide (LPS)-induced inflammation and in LPS treated AD APP/PS1 transgenic astrocytes. The function of Lat1 at the BBB was evaluated in wildtype mice with and without LPS-induced neuroinflammation and APP/PS1 transgenic mice by in situ brain perfusion. Read More

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http://dx.doi.org/10.1007/s11095-018-2546-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267245PMC
November 2018
4 Reads

Formulation and Manufacturing of Solid Dosage Forms.

Pharm Res 2018 Nov 27;36(1):16. Epub 2018 Nov 27.

Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA.

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http://dx.doi.org/10.1007/s11095-018-2547-6DOI Listing
November 2018
5 Reads

Measuring The Bipolar Charge Distributions of Fine Particle Aerosol Clouds of Commercial PMDI Suspensions Using a Bipolar Next Generation Impactor (bp-NGI).

Pharm Res 2018 Nov 26;36(1):15. Epub 2018 Nov 26.

Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK.

Purpose: To measure the charge to mass (Q/M) ratios of the impactor stage masses (ISM) from commercial Flixotide™ 250 μg Evohaler, containing fluticasone propionate (FP), Serevent™ 25 μg Evohaler, containing salmeterol xinafoate (SX), and a combination Seretide™ 250/25 μg (FP/SX) Evohaler metered dose inhalers (MDIs). Measurements were performed with a purpose built bipolar charge measurement apparatus (bp-NGI) based on an electrostatic precipitator, which was directly connected below Stage 2 of a Next Generation Impactor (NGI).

Methods: Five successive shots of the respective MDIs were actuated through the bp-NGI. Read More

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http://link.springer.com/10.1007/s11095-018-2544-9
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http://dx.doi.org/10.1007/s11095-018-2544-9DOI Listing
November 2018
21 Reads

Delivery of pDNA Polyplexes to Bronchial and Alveolar Epithelial Cells Using a Mesh Nebulizer.

Pharm Res 2018 Nov 15;36(1):14. Epub 2018 Nov 15.

Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, Sydney University, 431 Glebe Point Road, Glebe, Camperdown, NSW, 2037, Australia.

Purpose: In this study, a cell penetrating peptide was used as an uptake enhancer for pDNA delivery to the lungs.

Methods: Polyplexes were prepared between pDNA and CPP. Intracellular delivery of pDNA was assessed in both alveolar (A549) and bronchial (Calu-3) epithelial cells. Read More

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http://link.springer.com/10.1007/s11095-018-2542-y
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http://dx.doi.org/10.1007/s11095-018-2542-yDOI Listing
November 2018
10 Reads

Bioequivalence Study Methods with Pharmacokinetic Endpoints for Topical Ophthalmic Corticosteroid Suspensions and Effects of Subject Demographics.

Pharm Res 2018 Nov 15;36(1):13. Epub 2018 Nov 15.

Division of Bioequivalence II, Office of Bioequivalence, Office of Generic Drug, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.

Purpose: To establish bioequivalence for topical ophthalmic corticosteroid suspensions, some of U.S. product-specific guidances (PSGs) for generic drug products recommend evaluation of aqueous humor (AH) pharmacokinetics (PK). Read More

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http://link.springer.com/10.1007/s11095-018-2537-8
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http://dx.doi.org/10.1007/s11095-018-2537-8DOI Listing
November 2018
7 Reads

An Expandable Mechanopharmaceutical Device (1): Measuring the Cargo Capacity of Macrophages in a Living Organism.

Pharm Res 2018 Nov 12;36(1):12. Epub 2018 Nov 12.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.

Purpose: Clofazimine (CFZ) is an FDA-approved, poorly soluble small molecule drug that precipitates as crystal-like drug inclusions (CLDIs) which accumulate in acidic cytoplasmic organelles of macrophages. In this study, we considered CLDIs as an expandable mechanopharmaceutical device, to study how macrophages respond to an increasingly massive load of endophagolysosomal cargo.

Methods: First, we experimentally tested how the accumulation of CFZ in CLDIs impacted different immune cell subpopulations of different organs. Read More

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http://link.springer.com/10.1007/s11095-018-2539-6
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http://dx.doi.org/10.1007/s11095-018-2539-6DOI Listing
November 2018
15 Reads

Physicochemical Characterization and Pharmacokinetics of Agomelatine-Loaded PLGA Microspheres for Intramuscular Injection.

Pharm Res 2018 Nov 8;36(1). Epub 2018 Nov 8.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.

Purpose: The aim of this study was to design agomelatine loaded long acting injectable microspheres, with an eventual goal of reducing the frequency of administration and improving patient compliance in treatment of depression.

Methods: AGM-loaded microspheres were prepared by an O/W emulsion solvent evaporation method. The physicochemical properties and in vitro performance of the microspheres were characterized. Read More

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http://dx.doi.org/10.1007/s11095-018-2538-7DOI Listing
November 2018
14 Reads
3.420 Impact Factor

Stearic Acid-Grafted Chitooligosaccharide Nanomicelle System with Biocleavable Gadolinium Chelates as a Multifunctional Agent for Tumor Imaging and Drug Delivery.

Pharm Res 2018 Nov 8;36(1):10. Epub 2018 Nov 8.

Department of Pharmaceutical Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.

Purpose: Theranostic nanoplatforms are promising approaches for diagnosis and treatment. Here, we report a drug-loaded nanomicelle system with biocleavable gadolinium (Gd) chelates as a multifunctional biodegradable agent for simultaneous magnetic resonance imaging (MRI) and drug delivery.

Methods: Self-assembled nanomicelles based on stearic acid-grafted chitooligosaccharide were utilized as vehicles. Read More

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http://link.springer.com/10.1007/s11095-018-2530-2
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http://dx.doi.org/10.1007/s11095-018-2530-2DOI Listing
November 2018
11 Reads

New Classes of Polycationic Compounds as Preservatives for Ophthalmic Formulations.

Pharm Res 2018 Nov 8;36(1):11. Epub 2018 Nov 8.

Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany.

Purpose: The purpose of this research work was to develop new polycationic compounds based on pyridine and piperidine structures with high antimicrobial activities against bacteria and fungi. Furthermore, the compounds should offer a lower toxicity than the commonly used preservatives for ophthalmic formulations, such as benzalkonium chloride (BAC) and polyquaternium-1 (PQ1).

Methods: Two polymers and three dimeric compounds were developed. Read More

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http://link.springer.com/10.1007/s11095-018-2536-9
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http://dx.doi.org/10.1007/s11095-018-2536-9DOI Listing
November 2018
14 Reads

Mycobacterium Tuberculosis and Interactions with the Host Immune System: Opportunities for Nanoparticle Based Immunotherapeutics and Vaccines.

Pharm Res 2018 Nov 8;36(1). Epub 2018 Nov 8.

Discipline of Pharmaceutics, School of Pharmacy, University of the Western Cape, Cape Town, South Africa.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a deadly infectious disease. The thin pipeline of new drugs for TB, the ineffectiveness in adults of the only vaccine available, i.e. Read More

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http://link.springer.com/10.1007/s11095-018-2528-9
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http://dx.doi.org/10.1007/s11095-018-2528-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362825PMC
November 2018
13 Reads

Establishment of a Mucin Secreting Cell Line Cx-03 from an Uterine Carcino Sarcoma.

Pharm Res 2018 Nov 8;36(1). Epub 2018 Nov 8.

Department of Gynecology, Charite-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.

Purpose: The identification of novel cell lines which combine the most important properties of mucosal membranes in terms of drug absorption, transmembrane transport and mucus secretion can help to establish improved and meaningful test systems for pharmacological and infectiological studies.

Methods: We have established a novel mucus secreting tumor cell line (Cx-03) derived from a female patient who underwent radical hysterectomy after diagnosis of a large malignant carcino sarcoma (Muellerian mixed tumor). Via xenotransplantation in SCID beige mice, recultivation and subcloning a stable cell line was established from primary tumor cells. Read More

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http://link.springer.com/10.1007/s11095-018-2533-z
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http://dx.doi.org/10.1007/s11095-018-2533-zDOI Listing
November 2018
10 Reads

An Expandable Mechanopharmaceutical Device (2): Drug Induced Granulomas Maximize the Cargo Sequestering Capacity of Macrophages in the Liver.

Pharm Res 2018 Nov 7;36(1). Epub 2018 Nov 7.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109, USA.

Purpose: Drug-induced liver injuries (DILI) comprise a significant proportion of adverse drug reactions leading to hospitalizations and death. One frequent DILI is granulomatous inflammation from exposure to harmful metabolites that activate inflammatory pathways of immune cells of the liver, which may act as a barrier to isolate the irritating stimulus and limit tissue damage.

Methods: Paralleling the accumulation of CFZ precipitates in the liver, granulomatous inflammation was studied to gain insight into its effect on liver structure and function. Read More

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http://link.springer.com/10.1007/s11095-018-2541-z
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http://dx.doi.org/10.1007/s11095-018-2541-zDOI Listing
November 2018
7 Reads

Pharmaceutical Potential of a Novel Chitosan Derivative Schiff Base with Special Reference to Antibacterial, Anti-Biofilm, Antioxidant, Anti-Inflammatory, Hemocompatibility and Cytotoxic Activities.

Pharm Res 2018 Nov 7;36(1). Epub 2018 Nov 7.

Botany Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.

Purpose: Chitosan and its derivatives possess several unique properties relevant in the field of pharmaceutics and medicinal chemistry. This study aimed to evaluate the pharmaceutical performance of an innovative chitosan derivative, methyl acrylate chitosan bearing p-nitrobenzaldehyde (MA*CS*pNBA) Schiff base.

Methods: The antibacterial activity of MA*CS*pNBA was tested against multi-drug resistant (MDR) Gram-negative and Gram-positive bacteria using agar-well diffusion method. Read More

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http://link.springer.com/10.1007/s11095-018-2535-x
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http://dx.doi.org/10.1007/s11095-018-2535-xDOI Listing
November 2018
12 Reads

An Overview of 3D Printing Technologies for Soft Materials and Potential Opportunities for Lipid-based Drug Delivery Systems.

Pharm Res 2018 Nov 7;36(1). Epub 2018 Nov 7.

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Parkville, Victoria, 3052, Australia.

Purpose: Three-dimensional printing (3DP) is a rapidly growing additive manufacturing process and it is predicted that the technology will transform the production of goods across numerous fields. In the pharmaceutical sector, 3DP has been used to develop complex dosage forms of different sizes and structures, dose variations, dose combinations and release characteristics, not possible to produce using traditional manufacturing methods. However, the technology has mainly been focused on polymer-based systems and currently, limited information is available about the potential opportunities for the 3DP of soft materials such as lipids. Read More

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http://link.springer.com/10.1007/s11095-018-2531-1
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http://dx.doi.org/10.1007/s11095-018-2531-1DOI Listing
November 2018
5 Reads

Understanding the Impacts of Surface Compositions on the In-Vitro Dissolution and Aerosolization of Co-Spray-Dried Composite Powder Formulations for Inhalation.

Pharm Res 2018 Nov 7;36(1). Epub 2018 Nov 7.

Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA.

Purpose: Dissolution behavior of dry powder inhaler (DPI) antibiotic formulations in the airways may affect their efficacy especially for poorly-soluble antibiotics such as azithromycin. The main objective of this study was to understand the effects of surface composition on the dissolution of spray dried azithromycin powders by itself and in combination with colistin.

Methods: Composite formulations of azithromycin (a poorly water-soluble molecule) and colistin (a water-soluble molecule) were produced by spray drying. Read More

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http://dx.doi.org/10.1007/s11095-018-2527-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320342PMC
November 2018
2 Reads
3.420 Impact Factor