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Pharmaceutical Research

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https://www.readbyqxmd.com/read/30225831/genetic-basis-of-delayed-hypersensitivity-reactions-to-drugs-in-jewish-and-arab-populations
#1
REVIEW
Mohammed Aboukaoud, Shoshana Israel, Chaim Brautbar, Sara Eyal
Genetic variation can affect drug pharmacokinetics and pharmacodynamics and contribute to variability between individuals in response to medications. Specifically, differences in allele frequencies among individuals and ethnic groups have been associated with variation in their propensity to develop drug hypersensitivity reactions (HSRs). This article reviews the current knowledge on the genetic background of HSRs and its relevance to Jewish and Arab populations. The focus is on human leukocyte antigen (HLA) alleles and haplotypes as predictive markers of HSRs ("immunopharmacogenetics"), but other genes and alleles are described as well...
September 17, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30225649/using-human-plasma-as-an-assay-medium-in-caco-2-studies-improves-mass-balance-for-lipophilic-compounds
#2
Kasiram Katneni, Thao Pham, Jessica Saunders, Gong Chen, Rahul Patil, Karen L White, Nada Abla, Francis C K Chiu, David M Shackleford, Susan A Charman
PURPOSE: To examine the utility of human plasma as an assay medium in Caco-2 permeability studies to overcome poor mass balance and inadequate sink conditions frequently encountered with lipophilic compounds. METHODS: Caco-2 permeability was assessed for reference compounds with known transport mechanisms using either pH 7.4 buffer or human plasma as the assay medium in both the apical and basolateral chambers. When using plasma, Papp values were corrected for the unbound fraction in the donor chamber...
September 17, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30218393/can-population-modelling-principles-be-used-to-identify-key-pbpk-parameters-for-paediatric-clearance-predictions-an-innovative-application-of-optimal-design-theory
#3
Elisa A M Calvier, Thu Thuy Nguyen, Trevor N Johnson, Amin Rostami-Hodjegan, Dick Tibboel, Elke H J Krekels, Catherijne A J Knibbe
PURPOSE: Physiologically-based pharmacokinetic (PBPK) models are essential in drug development, but require parameters that are not always obtainable. We developed a methodology to investigate the feasibility and requirements for precise and accurate estimation of PBPK parameters using population modelling of clinical data and illustrate this for two key PBPK parameters for hepatic metabolic clearance, namely whole liver unbound intrinsic clearance (CLint,u,WL ) and hepatic blood flow (Qh) in children...
September 14, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30215146/drug-polymer-interaction-pharmacokinetics-and-antitumor-effect-of-peg-pla-taxane-derivative-tm-2-micelles-for-intravenous-drug-delivery
#4
Qiao Wang, Yi Liu, Chenguang Pu, Hongjuan Zhang, Xinyi Tan, Jingxin Gou, Haibing He, Tian Yin, Yu Zhang, Yanjiao Wang, Xing Tang
PURPOSE: A novel polymer micelle was prepared with a high drug loading, good stability, high tolerance and better anti-tumor effect. METHODS: TM-2 was encapsulated in poly-block-poly (D, L-lactic acid) self-assembled micelles by the thin-film hydration method. From the critical micelle concentrations of the copolymers, particle size, drug loading and encapsulation efficiency of drug-loading micelles, the appropriate polymer material could be assessed. Comparisons between TM-2 solution and TM-2 micelles were done to evaluate the pharmacokinetics and toxicity in rats, compared with Taxol to evaluate the anti-tumor effect in mice...
September 13, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30209680/ph-promoted-release-of-a-novel-anti-tumour-peptide-by-stealth-liposomes-effect-of-nanocarriers-on-the-drug-activity-in-cis-platinum-resistant-cancer-cells
#5
Francesca Sacchetti, Gaetano Marverti, Domenico D'Arca, Leda Severi, Eleonora Maretti, Valentina Iannuccelli, Salvatore Pacifico, Glauco Ponterini, Maria Paola Costi, Eliana Leo
PURPOSE: To evaluate the potential effects of PEGylated pH-sensitive liposomes on the intracellular activity of a new peptide recently characterized as a novel inhibitor of the human thymidylate synthase (hTS) over-expressed in many drug-resistant human cancer cell lines. METHODS: Peptide-loaded pH-sensitive PEGylated (PpHL) and non-PEGylated liposomes (nPpHL) were carefully characterized and delivered to cis-platinum resistant ovarian cancer C13* cells; the influence of the PpHL on the drug intracellular activity was investigated by the Western Blot analysis of proteins involved in the pathway affected by hTS inhibition...
September 12, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30209623/cationic-liposomes-a-flexible-vaccine-delivery-system-for-physicochemically-diverse-antigenic-peptides
#6
Jeroen Heuts, Eleni Maria Varypataki, Koen van der Maaden, Stefan Romeijn, Jan Wouter Drijfhout, Anton Terwisscha van Scheltinga, Ferry Ossendorp, Wim Jiskoot
PURPOSE: Personalized peptide-based cancer vaccines will be composed of multiple patient specific synthetic long peptides (SLPs) which may have various physicochemical properties. To formulate such SLPs, a flexible vaccine delivery system is required. We studied whether cationic liposomes are suitable for this purpose. METHODS: Fifteen SIINFEKL T cell epitope-containing SLPs, widely differing in hydrophobicity and isoelectric point, were separately loaded in cationic liposomes via the dehydration-rehydration method...
September 12, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30191400/molecular-targets-of-the-hydrophobic-block-of-pluronics-in-cells-a-photo-affinity-labelling-approach
#7
A Zhirnov, E Nam, G Badun, A Romanyuk, A Ezhov, N Melik-Nubarov, I Grozdova
PURPOSE: Pluronics are known as inhibitors of multidrug resistance thus making tumor cells sensitive to therapeutic doses of drugs. The purpose of our study consists in revealing molecular targets of the hydrophobic poly(propylene oxide) block of pluronics in living cells and the dependence of the polymers chemosensitizing efficiency upon targeting. METHODS: A photo sensitive tracer was attached to the hydrophobic poly(propylene oxide) block of 3 H-labeled tert-Bu-EO-PO copolymer...
September 6, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30191329/modeling-sex-differences-in-anti-inflammatory-effects-of-dexamethasone-in-arthritic-rats
#8
Dawei Song, Debra C DuBois, Richard R Almon, William J Jusko
PURPOSE: Collagen-induced arthritic (CIA) rats are used commonly for preclinical pharmacologic research into rheumatoid arthritis (RA). Dexamethasone (DEX), a potent corticosteroid (CS), remains an important component in combination therapy for RA. Although sex differences in RA and CS pharmacokinetics/pharmacodynamics (PK/PD) have been documented in humans, there has been no such comprehensive evaluation of sex differences in CIA rats. METHODS: Paw size measurements were obtained for males and females from four groups of animals: healthy controls, non-drug treated arthritic animals, and both 0...
September 6, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30191328/selective-inhibition-on-organic-cation-transporters-by-carvedilol-protects-mice-from-cisplatin-induced-nephrotoxicity
#9
Dong Guo, Hong Yang, Qing Li, Hyo Jung Bae, Obinna Obianom, Sujuan Zeng, Tong Su, James E Polli, Yan Shu
PURPOSE: The organic cation transporters (OCTs) and multidrug and toxin extrusions (MATEs), located in the basolateral and apical membrane of proximal tubular cells respectively, are crucial determinants of renal elimination and/or toxicity of cationic drugs such as cisplatin. The purpose of this study was to discover selective OCT inhibitors over MATEs, and explore their potential to protect against cisplatin-induced nephrotoxicity that is clinically common. METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1...
September 6, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30187188/co-delivery-of-teriflunomide-and-methotrexate-from-hydroxyapatite-nanoparticles-for-the-treatment-of-rheumatoid-arthritis-in-vitro-characterization-pharmacodynamic-and-biochemical-investigations
#10
Shweta Pandey, Vijay Kumar, Ankita Leekha, Nishant Rai, Farhan Jalees Ahmad, Anita Kamra Verma, Sushama Talegaonkar
PURPOSE: The present investigation was aimed at developing Teriflunomide (TEF) and Methotrexate (MTX) loaded hydroxyapatite nanoparticles and increasing tolerability towards combination therapy against rheumatoid arthritis by reducing hepatotoxicity. METHODS: Drug-loaded HAp-NPs were synthesized by wet-chemical precipitation method and optimized by Box-Behnken experimental design. The developed NPs were subjected to in vitro and in vivo characterization. In-vivo pharmacodynamics and biochemical studies were performed on adjuvant- induced arthritis model treated with different formulations; MTX-TEF-SOL, TEF-HAp-NP, MTX-HAp-NP, TEF-MTX-HAp-NP, FOLITRAX-10 and AUBAGIO...
September 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30187140/correction-to-bioreducible-poly-amino-ethers-based-mtor-sirna-delivery-for-lung-cancer
#11
Nishant S Gandhi, Sudhakar Godeshala, Dana-Lynn T Koomoa-Lange, Bhavani Miryala, Kaushal Rege, Mahavir B Chougule
Under the heading "Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)", on page 3, line 14-17, there is an error. The quantity unit of PAE and 2-iminothiolane hydrochloride needs to be corrected to mg instead of g.
September 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30171428/radiolabeled-plga-nanoparticles-for-effective-targeting-of-bendamustine-in-tumor-bearing-mice
#12
Iliyas Khan, Avinash Gothwal, Ankur Kaul, Rashi Mathur, Anil Kumar Mishra, Umesh Gupta
PURPOSE: Bendamustine is an important drug for the treatment of chronic lymphatic leukaemia (CLL), non-Hodgkin lymphoma (NHL). However, its delivery is challenging due to its instability. Current approach reports the development and characterization of bendamustine encapsulated PLGA nanoparticles for the effective targeting to leukemic cells. METHODS: The prepared, bendamustine loaded PLGA nanoparticles (BLPNP) were developed and characterized for particle size, zeta potential and polydispersity index...
August 31, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30167890/fabrication-of-tpgs-stabilized-liposome-plga-hybrid-nanoparticle-via-a-new-modified-nanoprecipitation-approach-in-vitro-and-in-vivo-evaluation
#13
Mengyuan Zhang, Jianhua He, Wenli Zhang, Jianping Liu
PURPOSE: In this study, a new modified nanoprecipitation approach that more efficient and simpler than conventional approach was developed to synthesize D-alpha-Tocopheryl polyethylene glycol 1000 succinate stabilized liposome-PLGA hybrid nanoparticle, loaded with simvastatin (ST-TLPN). METHODS: The optimum formulation was screened via investigation of the impact of TPGS mass within polymeric core and lipid shell on the physicochemical properties of nanoparticles respectively...
August 30, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30151753/orcinol-glucoside-loaded-polymer-lipid-hybrid-nanostructured-lipid-carriers-potential-cytotoxic-agents-against-gastric-colon-and-hepatoma-carcinoma-cell-lines
#14
Prasant Nahak, Rahul L Gajbhiye, Gourab Karmakar, Pritam Guha, Biplab Roy, Shila Elizabeth Besra, Alexey G Bikov, Alexander V Akentiev, Boris A Noskov, Kaushik Nag, Parasuraman Jaisankar, Amiya Kumar Panda
PURPOSE: Orcinol glucoside (OG) - loaded nanostructured lipid carrier (NLC), coated with polyethylene glycol-25/55-stearate (PEG-25/55-SA), were explored for delivering OG to improve in vitro cytotoxicity against gastrointestinal tract (GIT), colon and hepatoma carcinoma cell lines. It is being expected that the PEGylated formulations would possess the sustainability in withstanding the adverse physiological extremities like the most significant metabolic activities and phase I / II enzymatic activities in the intestines...
August 27, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30143878/hyaluronic-acid-layer-by-layer-lbl-nanoparticles-for-synergistic-chemo-phototherapy
#15
Juan Zhao, Zhuoya Wan, Chuchu Zhou, Qin Yang, Jianxia Dong, Xu Song, Tao Gong
PURPOSE: The aim of this study was to design hyaluronic acid (HA) layer-by-layer (LbL) nanoparticles, which carried paclitaxel (PTX) and Indocyanine green (ICG) to both tumor cells and tumor associated cells to achieve synergistic chemo-photothermal therapeutic effect. METHODS: The LbL-engineered nanoparticles (PDIH) were prepared by dopamine self-polymerization on PTX nanocrystal to form thin, surface-adherent polydopamine (PDA) films, which subsequently absorbed ICG and HA...
August 24, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30143865/in-silico-prediction-of-major-clearance-pathways-of-drugs-among-9-routes-with-two-step-support-vector-machines
#16
Naomi Wakayama, Kota Toshimoto, Kazuya Maeda, Shun Hotta, Takashi Ishida, Yutaka Akiyama, Yuichi Sugiyama
PURPOSE: The clearance pathways of drugs are critical elements for understanding the pharmacokinetics of drugs. We previously developed in silico systems to predict the five clearance pathway using a rectangular method and a support vector machine (SVM). In this study, we improved our classification system by increasing the number of clearance pathways available for our prediction (CYP1A2, CYP2C8, CYP2C19, and UDP-glucuronosyl transferases (UGTs)) and by accepting multiple major pathways...
August 24, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30141117/formulation-of-high-performance-dry-powder-aerosols-for-pulmonary-protein-delivery
#17
Erin M Wilson, J Christopher Luft, Joseph M DeSimone
PURPOSE: Pulmonary delivery of biologics is of great interest, as it can be used for the local treatment of respiratory diseases or as a route to systemic drug delivery. To reach the full potential of inhaled biologics, a formulation platform capable of producing high performance aerosols without altering protein native structure is required. METHODS: A formulation strategy using Particle Replication in Non-wetting Templates (PRINT) was developed to produce protein dry powders with precisely engineered particle morphology...
August 23, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30132207/efficient-nose-to-lung-aerosol-delivery-with-an-inline-dpi-requiring-low-actuation-air-volume
#18
Dale Farkas, Michael Hindle, P Worth Longest
PURPOSE: To demonstrate efficient aerosol delivery through an in vitro nasal model using a dry powder inhaler (DPI) requiring low actuation air volumes (LV) applied during low-flow nasal cannula (LFNC) therapy. METHODS: A previously developed LV-DPI was connected to a LFNC system with 4 mm diameter tubing. System connections and the nasal cannula interface were replaced with streamlined components. To simulate nasal respiration, an in vitro nasal model was connected to a downstream lung simulator that produced either passive or deep nasal respiration...
August 21, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30128780/in-silico-prediction-of-diffusion-interaction-parameter-k-d-a-key-indicator-of-antibody-solution-behaviors
#19
Dheeraj S Tomar, Satish K Singh, Li Li, Matthew P Broulidakis, Sandeep Kumar
PURPOSE: To develop resource-sparing in silico approaches that aim to reduce experimental effort and material required by developability assessments (DA) of monoclonal antibody (mAb) drug candidates. METHODS: A battery of standardized biophysical experiments was performed on high concentration formulations of 16 drug product development stage mAbs using a platform buffer. Full-length molecular models of these mAbs were also generated via molecular modeling. These models were used to computationally estimate molecular descriptors of these 16 mAbs...
August 20, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30116974/doing-it-all-how-families-are-reshaping-rare-disease-research
#20
Sean Ekins, Ethan O Perlstein
The face of rare disease drug discovery and development is changing right before our eyes. The outliers of the past were the plucky parents who summoned up the courage to try to treat their children against all odds. Think of the rare disease focused movies 'Lorenzo's Oil' and 'Extraordinary Measures' but now accelerated to develop treatments even quicker. Parents, patient advocates and their collaborators are now capable of doing it all themselves. We think this will have profound implications for everyone from the incumbent rare disease foundations that have held sway for decades to the multibillion dollar rare disease market, BioPharma companies, VCs and angel investors that inhabit this space...
August 16, 2018: Pharmaceutical Research
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