8,785 results match your criteria Pharmaceutical research[Journal]


Transport Mechanisms for the Nutritional Supplement β-Hydroxy-β-Methylbutyrate (HMB) in Mammalian Cells.

Pharm Res 2019 Apr 17;36(6):84. Epub 2019 Apr 17.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430-6540, USA.

Purpose: β-Hydroxy-β-methylbutyrate (HMB), a nutritional supplement, elicits anabolic activity in muscle. Here we investigated the mechanism of HMB uptake in muscle cells.

Methods: Murine muscle cells (C2C12) and human mammary epithelial cells (MCF7) were used for uptake. Read More

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http://dx.doi.org/10.1007/s11095-019-2626-3DOI Listing

Polymeric Micellar Formulation Enhances Antimicrobial and Anticancer Properties of Salinomycin.

Pharm Res 2019 Apr 15;36(6):83. Epub 2019 Apr 15.

Pharmacological and Regulatory Sciences Group (PharmaRegSci), Research Institute for Medicines (iMed.ULisboa), Faculdadde de Farmácia da Universidade de Lisboa, Lisbon, Portugal.

Purpose: Salinomycin (SAL) is a polyether compound that exhibits strong antimicrobial as well as anticancer activity. Nanomedicine has been at the forefront of drug delivery research with the aim of increasing the efficacy, specificity and reduce toxicity of drugs. There is an intersection between infection and cancer, and cancer patients are prone to bacterial infections. Read More

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http://dx.doi.org/10.1007/s11095-019-2615-6DOI Listing

Concentration and Glycoform of Rituximab in Plasma of Patients with B Cell Non-Hodgkin's Lymphoma.

Pharm Res 2019 Apr 15;36(6):82. Epub 2019 Apr 15.

Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: Therapeutic antibodies have heterogeneities in their structures, although its structural alteration in the body is unclear. Here, we analyzed the change of amino acid modifications and carbohydrate chains of rituximab after administration to patients.

Methods: Twenty B cell non-Hodgkin's lymphoma patients who were treated with rituximab for the first time or after more than one year's abstinence were recruited. Read More

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http://dx.doi.org/10.1007/s11095-019-2624-5DOI Listing
April 2019
1 Read

Lipid-Coated, pH-Sensitive Magnesium Phosphate Particles for Intracellular Protein Delivery.

Pharm Res 2019 Apr 11;36(6):81. Epub 2019 Apr 11.

Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, California, 95211, USA.

Purpose: To develop cationic lipid-coated magnesium phosphate nanoparticles (LPP) for intracellular catalase (CAT) delivery.

Methods: Magnesium phosphate nanoparticles (MgP NP) were prepared by micro-emulsion precipitation and mixed with catalase-loaded cationic liposomes (DOTAP/cholesterol) to yield LPP formulation of catalase (LPP-CAT). The size and ζ-potential of LPP-CAT were measured by dynamic light scattering. Read More

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http://dx.doi.org/10.1007/s11095-019-2607-6DOI Listing
April 2019
2 Reads

Tribo-Charging Behaviour of Inhalable Mannitol Blends with Salbutamol Sulphate.

Pharm Res 2019 Apr 9;36(6):80. Epub 2019 Apr 9.

Research Center Pharmaceutical Engineering GmbH, 8010, Graz, Austria.

Purpose: The performance of carrier-based dry powder inhaler (DPI) formulations can be critically impacted by interfacial interactions driven by tribo-electrification. Therefore, the aim of the present work was to understand how distinct API particle characteristics affect the charging behaviour of blends intended for DPI delivery.

Methods: Salbutamol sulphate (SBS) particles engineered via spray-drying and jet milling were used as model APIs. Read More

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http://link.springer.com/10.1007/s11095-019-2612-9
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http://dx.doi.org/10.1007/s11095-019-2612-9DOI Listing
April 2019
2 Reads

Identification of Lysine Misincorporation at Asparagine Position in Recombinant Insulin Analogs Produced in E. coli.

Pharm Res 2019 Apr 4;36(6):79. Epub 2019 Apr 4.

National Medicines Institute, Chełmska 30/34, 00-725, Warsaw, Poland.

Purpose: Identification of human insulin analogs' impurity with a mass shift +14 Da in comparison to a parent protein.

Methods: The protein sequence variant was detected and identified with the application of peptide mapping, liquid chromatography, tandem mass spectrometric analysis, nuclear magnetic resonance spectroscopy (NMR) and Edman sequencing.

Results: The misincorporated lysine (Lys) at asparagine (Asn) position A21 was detected in recombinant human insulin and its analogs. Read More

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http://link.springer.com/10.1007/s11095-019-2601-z
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http://dx.doi.org/10.1007/s11095-019-2601-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449291PMC
April 2019
1 Read

Biomedical Imaging: Principles, Technologies, Clinical Aspects, Contrast Agents, Limitations and Future Trends in Nanomedicines.

Pharm Res 2019 Apr 3;36(6):78. Epub 2019 Apr 3.

Université de Strasbourg, CNRS, CAMB UMR 7199, F-67000, Strasbourg, France.

This review article presents the state-of-the-art in the major imaging modalities supplying relevant information on patient health by real-time monitoring to establish an accurate diagnosis and potential treatment plan. We draw a comprehensive comparison between all imagers and ultimately end with our focus on two main types of scanners: X-ray CT and MRI scanners. Numerous types of imaging probes for both imaging techniques are described, as well as reviewing their strengths and limitations, thereby showing the current need for the development of new diagnostic contrast agents (CAs). Read More

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http://link.springer.com/10.1007/s11095-019-2608-5
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http://dx.doi.org/10.1007/s11095-019-2608-5DOI Listing
April 2019
1 Read

Direct Drug Delivery of Low-Permeable Compounds to the Central Nervous System Via Intranasal Administration in Rats and Monkeys.

Pharm Res 2019 Apr 1;36(5):76. Epub 2019 Apr 1.

Drug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Co., Ltd., 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.

Purpose: Intranasal administration enhances drug delivery to the brain by allowing targeted-drug delivery. Here, we investigated the properties that render a compound suitable for intranasal administration, and the differences between rodents and non-human primates in delivery to the brain.

Methods: The delivery of 10 low-permeable compounds to the brain, including substrates of efflux drug transporters expressed in the blood-brain barrier (didanosine, metformin, zolmitriptan, cimetidine, methotrexate, talinolol, ranitidine, atenolol, furosemide, and sulpiride) and two high-permeable compounds (ropinirole and midazolam) was evaluated following intranasal and intravenous administration in rats. Read More

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http://dx.doi.org/10.1007/s11095-019-2613-8DOI Listing
April 2019
2 Reads

How Full-Length FVIII Benefits from Its Heterogeneity - Insights into the Role of the B-Domain.

Pharm Res 2019 Apr 1;36(5):77. Epub 2019 Apr 1.

Research & Development, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.

Purpose: To explore how the natural heterogeneity of human coagulation factor VIII (FVIII) and the processing of its B-domain specifically modulate protein aggregation.

Methods: Recombinant FVIII (rFVIII) molecular species containing 70% or 20% B-domain, and B-domain-deleted rFVIII (BDD-rFVIII), were separated from full-length recombinant FVIII (FL-rFVIII). Purified human plasma-derived FVIII (pdFVIII) was used as a comparator. Read More

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http://dx.doi.org/10.1007/s11095-019-2599-2DOI Listing

Cefquinome-Loaded Microsphere Formulations in Protection against Pneumonia with Klebsiella pneumonia Infection and Inflammatory Response in Rats.

Pharm Res 2019 Mar 28;36(5):74. Epub 2019 Mar 28.

College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266109, China.

Purpose: This study aimed to compare in vivo activity between cefquinome (CEQ)-loaded poly lactic-co-glycolic acid (PLGA) microspheres (CEQ-PLGA-MS) and CEQ injection (CEQ-INJ) against Klebsiella pneumonia in a rat lung infection model.

Methods: Forty-eight rats were divided into control group (sham operated without infection and drug treatment), Klebsiella pneumonia model group (KPD + Saline), CEQ-PLGA-MS and CEQ-INJ therapy groups (KPD + CEQ-PLGA-MS and KPD + INJ, respectively). In the KPD + Saline group, rats were infected with Klebsiella pneumonia ATCC 10031. Read More

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http://dx.doi.org/10.1007/s11095-019-2614-7DOI Listing
March 2019
2 Reads

Mathematical Modeling and Simulation to Investigate the CNS Transport Characteristics of Nanoemulsion-Based Drug Delivery Following Intranasal Administration.

Pharm Res 2019 Mar 28;36(5):75. Epub 2019 Mar 28.

Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, 02115, USA.

Purpose: Despite encouraging preclinical results, mechanisms of CNS drug delivery following intranasal dosing of nanoemulsions remain incompletely understood. Herein, the transport characteristics of intranasally administered nanoemulsions are investigated using mathematical modeling and simulation.

Methods: A compartmental model was developed to describe systemic and brain pharmacokinetics of drug solutions following intranasal dosing in rodents. Read More

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http://dx.doi.org/10.1007/s11095-019-2610-yDOI Listing
March 2019
1 Read

Antiretroviral Hydrophobic Core Graft-Copolymer Nanoparticles: The Effectiveness against Mutant HIV-1 Strains and in Vivo Distribution after Topical Application.

Pharm Res 2019 Mar 27;36(5):73. Epub 2019 Mar 27.

Laboratory of Molecular Imaging Probes, Department of Radiology, University of Massachusetts Medical School, S6-434, 55 Lake Ave North, Worcester, MA, 01655, USA.

Purpose: Developing and testing of microbicides for pre-exposure prophylaxis and post-exposure protection from HIV are on the list of major HIV/AIDS research priorities. To improve solubility and bioavailability of highly potent anti-retroviral drugs, we explored the use of a nanoparticle (NP) for formulating a combination of two water-insoluble HIV inhibitors.

Methods: The combination of a non-nucleoside HIV reverse transcriptase inhibitor (NNRTI), Efavirenz (EFV), and an inhibitor of HIV integrase, Elvitegravir (ELV) was stabilized with a graft copolymer of methoxypolyethylene glycol-polylysine with a hydrophobic core (HC) composed of fatty acids (HC-PGC). Read More

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http://dx.doi.org/10.1007/s11095-019-2604-9DOI Listing
March 2019
1 Read

Effects of Temperature and Ionic Strength of Dissolution Medium on the Gelation of Amorphous Lurasidone Hydrochloride.

Pharm Res 2019 Mar 26;36(5):72. Epub 2019 Mar 26.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198,, People's Republic of China.

Purpose: Amorphous lurasidone hydrochloride (LH) showed decreased dissolution behavior in comparison to crystalline LH owing to gelation during dissolution as reported in our previous study. The current study aims to investigate external factors including temperature and ionic strength on the gelation and hence the dissolution of amorphous LH.

Methods: Dissolution tests of amorphous LH were performed under different temperatures and buffer ionic strengths. Read More

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http://link.springer.com/10.1007/s11095-019-2611-x
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http://dx.doi.org/10.1007/s11095-019-2611-xDOI Listing
March 2019
4 Reads

Application of Magnetic Resonance to Assess Lyophilized Drug Product Reconstitution.

Pharm Res 2019 Mar 22;36(5):71. Epub 2019 Mar 22.

Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.

Purpose: Dynamic in-situ proton (H) magnetic resonance imaging (MRI) and H T-relaxometry experiments are described in an attempt to: (i) understand the physical processes, that occur during the reconstitution of lyophilized bovine serum albumin (BSA) and monoclonal antibody (mAb) proteins; and (ii) objectify the reconstitution time.

Methods: Rapid two-dimensional H MRI and diffusion weighted MRI were used to study the temporal changes in solids dissolution and characterise water mass transport characteristics. One-shot T relaxation time measurements were also acquired in an attempt to quantify the reconstitution time. Read More

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http://link.springer.com/10.1007/s11095-019-2591-x
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http://dx.doi.org/10.1007/s11095-019-2591-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430757PMC
March 2019
5 Reads

Oligo(Lactic Acid)-Rapamycin Prodrug-Loaded Poly(Ethylene Glycol)-block-Poly(Lactic Acid) Micelles for Injection.

Pharm Res 2019 Mar 19;36(5):70. Epub 2019 Mar 19.

Pharmaceutical Sciences Division, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin, 53705-2222, USA.

Purpose: To prepare an oligo(lactic acid)-rapamycin prodrug (o(LA)-RAP)-loaded poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelle for injection and characterize its compatibility and performance versus a RAP-loaded PEG-b-PLA micelle for injection in vitro and in vivo.

Methods: Monodisperse o(LA) was coupled on RAP at the C-40 via DCC/DMAP chemistry, and conversion of o(LA)-RAP prodrug into RAP was characterized in vitro. Physicochemical properties of o(LA)-RAP- and RAP-loaded PEG-b-PLA micelles and their antitumor efficacies in a syngeneic 4 T1 breast tumor model were compared. Read More

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http://dx.doi.org/10.1007/s11095-019-2600-0DOI Listing
March 2019
6 Reads

Ophthalmic Drug Discovery and Development.

Pharm Res 2019 03 18;36(5):69. Epub 2019 Mar 18.

Allergan plc., Pharmaceutical Development, Irvine, California, USA.

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http://dx.doi.org/10.1007/s11095-019-2606-7DOI Listing

Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model.

Pharm Res 2019 Mar 18;36(5):68. Epub 2019 Mar 18.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Purpose: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems.

Methods: A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues. Read More

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http://dx.doi.org/10.1007/s11095-019-2598-3DOI Listing
March 2019
1 Read
3.420 Impact Factor

Improving Stability and Dissolution of Amorphous Clofazimine by Polymer Nano-Coating.

Pharm Res 2019 Mar 15;36(5):67. Epub 2019 Mar 15.

School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA.

Purpose: To inhibit the surface crystallization and enhance the dissolution of the basic amorphous drug clofazimine by polymer nano-coating.

Methods: The free surface of amorphous clofazimine was coated by dip coating in an alginate solution at pH 7. The stability of the coated amorphous drug against crystallization was evaluated by X-ray diffraction and light microscopy. Read More

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http://dx.doi.org/10.1007/s11095-019-2584-9DOI Listing

Efficacy of Surface-Modified PLGA Nanoparticles as a Function of Cervical Cancer Type.

Pharm Res 2019 Mar 13;36(5):66. Epub 2019 Mar 13.

Department of Bioengineering, University of Louisville, 505 S. Hancock, CTR 623, Louisville, Kentucky, 40202, USA.

Purpose: Hypovascularization of cervical tumors, coupled with intrinsic and acquired drug resistance, has contributed to marginal therapeutic outcomes by hindering chemotherapeutic transport and efficacy. Recently, the heterogeneous penetration and distribution of cell penetrating peptide (CPP, here MPG) and polyethylene glycol (PEG) modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were evaluated as a function of tumor type and morphology in cervical cancer spheroids modeling hypovascularized tumor nodules. Building upon this work, this study investigates the efficacy imparted by surface-modified Doxorubicin-loaded NPs transported into hypovascularized tissue. Read More

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http://dx.doi.org/10.1007/s11095-019-2602-yDOI Listing
March 2019
1 Read

Surface Modification of Polymeric Nanoparticles with M2pep Peptide for Drug Delivery to Tumor-Associated Macrophages.

Pharm Res 2019 Mar 11;36(4):65. Epub 2019 Mar 11.

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

Purpose: Tumor-associated macrophages (TAMs) with immune-suppressive M2-like phenotype constitute a significant part of tumor and support its growth, thus making an attractive therapeutic target for cancer therapy. To improve the delivery of drugs that control the survival and/or functions of TAMs, we developed nanoparticulate drug carriers with high affinity for TAMs.

Methods: Poly(lactic-co-glycolic acid) nanoparticles were coated with M2pep, a peptide ligand selectively binding to M2-polarized macrophages, via a simple surface modification method based on tannic acid-iron complex. Read More

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http://dx.doi.org/10.1007/s11095-019-2596-5DOI Listing
March 2019
2 Reads

A Macromolecular Janus Kinase (JAK) Inhibitor Prodrug Effectively Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

Pharm Res 2019 Mar 11;36(4):64. Epub 2019 Mar 11.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 986125 Nebraska Medical Center, PDD 3020, Omaha, NE, 68198-6125, USA.

Background: Tofacitinib (Tofa) has been approved for moderately to severely active ulcerative colitis (UC). To improve its therapeutic efficacy and limit dose-dependent toxicity, we developed a macromolecular prodrug of Tofa (P-Tofa). If the prodrug design improves the potency and duration of Tofa therapy, it would widen its therapeutic window, potentially leading to improved safety and better clinical management of UC. Read More

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http://dx.doi.org/10.1007/s11095-019-2587-6DOI Listing
March 2019
1 Read

Nanomedicines for Infectious Diseases.

Authors:
Admire Dube

Pharm Res 2019 Mar 11;36(4):63. Epub 2019 Mar 11.

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

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http://dx.doi.org/10.1007/s11095-019-2603-xDOI Listing

A Comprehensive Physicochemical, In Vitro and Molecular Characterization of Letrozole Incorporated Chitosan-Lipid Nanocomplex.

Pharm Res 2019 Mar 8;36(4):62. Epub 2019 Mar 8.

Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran.

Purpose: The aim of this study is to show a new mesomicroscopic insight into Letrozole (LTZ) loaded nanocomplexes and their ex vivo characteristics as a drug delivery system.

Methods: The LTZ loaded hybrid chitosan-based carrier was fabricated using a modified ionic crosslinking technique and characterized in more detail. To understand the mechanism of LTZ action encapsulated in the hybrid polymer-lipid carrier, all-atom molecular dynamics simulations were also used. Read More

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http://link.springer.com/10.1007/s11095-019-2597-4
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http://dx.doi.org/10.1007/s11095-019-2597-4DOI Listing
March 2019
7 Reads
3.420 Impact Factor

A Multifunctional Hydrogel Delivers Gold Compound and Inhibits Human Lung Cancer Xenograft.

Pharm Res 2019 Mar 8;36(4):61. Epub 2019 Mar 8.

Department of Chemistry and Chemical Biology Centre, The University of Hong Kong, Pokfulam, Hong Kong.

Purpose: Interpenetrating network system (IPN), consisting of polyethylene glycol (PEG) -diacrylate (PEGdA) and modified gelatin, is a biocompatible and biodegradable hydrogel and has been studied for the local delivery of bioactive molecules and drugs. Gold(III) porphyrin(AuP) is a stable metal compound in the development for anticancer application when administered systemically. The aim of this work is to develop a novel formulation for AuP based on IPN for local delivery. Read More

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http://dx.doi.org/10.1007/s11095-019-2581-zDOI Listing
March 2019
1 Read

Biomimetic Hydroxyapatite a Potential Universal Nanocarrier for Cellular Internalization & Drug Delivery.

Pharm Res 2019 Mar 7;36(4):60. Epub 2019 Mar 7.

Department of Chemical Engineering, Institute of Chemical Technology, Matunga (E), Mumbai, 400019, India.

Purpose: Functional biomaterials can be used as drug loading devices, components for tissue engineering or as biological probes. As such, the design, synthesis and evaluation of a variety of local-drug delivery structures has been undertaken over the past few decades with the ultimate aim of providing materials that can encapsulate a diverse array of drugs (in terms of their sizes, chemical compositions and chemical natures (i.e. Read More

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http://dx.doi.org/10.1007/s11095-019-2594-7DOI Listing
March 2019
10 Reads

Recovery of OATP1B Activity after Living Kidney Transplantation in Patients with End-Stage Renal Disease.

Pharm Res 2019 Feb 26;36(4):59. Epub 2019 Feb 26.

Department of Clinical Pharmacy, Oita University Hospital, 1-1 Hasama-machi, Oita, 879-5593, Japan.

Purpose: Recently, several studies have shown that renal failure decreases the metabolic clearance of drugs and the transportation capability of some drug transporters. However, whether organic anion transporting polypeptide (OATP)1B activities decrease in renal failure remains unknown. In this study, we measured plasma concentrations of coproporphyrin-I (CP-I), a specific endogenous OATP1B probe, in patients with end stage renal disease before and after living kidney transplantation and evaluated the effect of renal function on OATP1B activity. Read More

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http://dx.doi.org/10.1007/s11095-019-2593-8DOI Listing
February 2019

Translational Preclinical Pharmacologic Disease Models for Ophthalmic Drug Development.

Pharm Res 2019 Feb 25;36(4):58. Epub 2019 Feb 25.

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

Preclinical models of human diseases are critical to our understanding of disease etiology, pathology, and progression and enable the development of effective treatments. An ideal model of human disease should capture anatomical features and pathophysiological mechanisms, mimic the progression pattern, and should be amenable to evaluating translational endpoints and treatment approaches. Preclinical animal models have been developed for a variety of human ophthalmological diseases to mirror disease mechanisms, location of the affected region in the eye and severity. Read More

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http://dx.doi.org/10.1007/s11095-019-2588-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394514PMC
February 2019
1 Read

New Insights into Using Lipid Based Suspensions for 'Brick Dust' Molecules: Case Study of Nilotinib.

Pharm Res 2019 Feb 22;36(4):56. Epub 2019 Feb 22.

School of Pharmacy, University College Cork, Cavanagh Building, College Road, Cork, Ireland.

Purpose: Lipid suspensions have been shown to be a suitable bio-enabling formulation approach for highly lipophilic or 'grease ball' drug molecules, but studies on 'brick dust' drugs are lacking. This study explored the utility of lipid suspensions for enhancing oral bioavailability of the rather hydrophobic drug nilotinib in vivo in rats.

Methods: Four lipid suspensions were developed containing long chain triglycerides, medium chain triglyceride, long chain monoglycerides and medium chain monoglycerides and in vivo bioavailability was compared to an aqueous suspension. Read More

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http://dx.doi.org/10.1007/s11095-019-2590-yDOI Listing
February 2019

A Theoretical Model for the Cell Cycle and Drug Induced Cell Cycle Arrest of FUCCI Systems with Cell-to-Cell Variation during Mitosis.

Pharm Res 2019 Feb 22;36(4):57. Epub 2019 Feb 22.

College of Pharmacy, Seoul National University, 1 Gwanak-ro Gwanak-gu, Seoul, 08826, South Korea.

Purpose: Since the molecular mechanism of the cell cycle was established, various theoretical models of this process have been developed. A recent study revealed significant variability in cell cycle duration between mother and daughter cells, but this observation has not been incorporated into the theoretical models.

Methods: We used fluorescent ubiquitination-based cell cycle indicator (FUCCI) systems and live-monitored the heterogeneity of cell cycle progression within daughter cells, which accounts for dephasing synchrony. Read More

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http://dx.doi.org/10.1007/s11095-019-2570-2DOI Listing
February 2019
2 Reads

Metal Organic Framework (MOF) Particles as Potential Bacteria-Mimicking Delivery Systems for Infectious Diseases: Characterization and Cellular Internalization in Alveolar Macrophages.

Pharm Res 2019 Feb 21;36(4):53. Epub 2019 Feb 21.

Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, South Dakota State University, 1055 Campanile Avenue, Avera Health Science Building, Brookings, SD, 57007, USA.

Purpose: Intramacrophagic bacteria pose a great challenge for the treatment of infectious diseases despite many macrophage targeted drug delivery approaches explored. The use of biomimetic approaches for treating infectious diseases is promising, but not studied extensively. The study purpose is to evaluate iron-based metal-organic frameworks (MOF) as a potential bacteria-mimicking delivery system for infectious diseases. Read More

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http://dx.doi.org/10.1007/s11095-019-2589-4DOI Listing
February 2019
1 Read

Ophthalmic Drug Discovery and Development: Regulatory Aspects of Patient Focused Drug Development in Ophthalmology.

Pharm Res 2019 Feb 21;36(4):54. Epub 2019 Feb 21.

Ophthalmic Medical and Research Consulting, Omar Consulting Group, LLC, Princeton Junction, NJ, 08550, USA.

In 2009, members of the ophthalmic research community held a joint meeting with members of the Food and Drug Administration (FDA) and the National Eye Institute (NEI) to define and describe the types of patient-focused drug development (PFDD) tools used in ophthalmology. Since then numerous reports have been published which indicate that many of the questionnaires used for patient-reported outcomes (PROs) in ophthalmic clinical development lack rigor and reliability according to modern methods. In 2017, the FDA began development of a series of four methodological guidances for sponsors of clinical trials on the significance of PFDD. Read More

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http://dx.doi.org/10.1007/s11095-019-2577-8DOI Listing
February 2019

Correction to: Comparative Study of the Dose-Dependence of OATP1B Inhibition by Rifampicin Using Probe Drugs and Endogenous Substrates in Healthy Volunteers.

Pharm Res 2019 02 21;36(4):55. Epub 2019 Feb 21.

Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

There was a miscalculation of coproporphyrin I AUC in the published article (Volume 35, Number 7). After the correction of AUC, AUC ratio and R-square were re-calculated. Then, following corrections were made in the abstract, the body, Fig. Read More

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http://dx.doi.org/10.1007/s11095-019-2585-8DOI Listing
February 2019

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://link.springer.com/10.1007/s11095-019-2586-7
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http://dx.doi.org/10.1007/s11095-019-2586-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394513PMC
February 2019
2 Reads

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
4 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373292PMC
February 2019
7 Reads

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373306PMC
February 2019
5 Reads

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373530PMC
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
7 Reads

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
5 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
1 Read

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
11 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
14 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
12 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
25 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
22 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
10 Reads