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Pharmaceutical Research

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https://www.readbyqxmd.com/read/30421091/an-expandable-mechanopharmaceutical-device-1-measuring-the-cargo-capacity-of-macrophages-in-a-living-organism
#1
Phillip Rzeczycki, Tehetina Woldemichael, Andrew Willmer, Mikhail D Murashov, Jason Baik, Rahul Keswani, Gi Sang Yoon, Kathleen A Stringer, Nair Rodriguez-Hornedo, Gus R Rosania
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...
November 12, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30411255/physicochemical-characterization-and-pharmacokinetics-of-agomelatine-loaded-plga-microspheres-for-intramuscular-injection
#2
Hongjuan Zhang, Chenguang Pu, Qiao Wang, Xinyi Tan, Jingxin Gou, Haibing He, Yu Zhang, Tian Yin, Yanjiao Wang, Xing Tang
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. The pharmacokinetics of different formulations with various particle sizes and drug loadings were evaluated...
November 8, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30411214/stearic-acid-grafted-chitooligosaccharide-nanomicelle-system-with-biocleavable-gadolinium-chelates-as-a-multifunctional-agent-for-tumor-imaging-and-drug-delivery
#3
Chuhua Xin, Xiuzhong Yao, Bin Du, Weiyu Yang, Liuguo Wang, Lirong Ma, Weiyu Weng
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. Gd chelates, DTPA-Gds, were linked to the nanomicelles via redox-responsive disulfide bonds, and hydrophobic drugs were encapsulated in the micelle cores...
November 8, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30411196/new-classes-of-polycationic-compounds-as-preservatives-for-ophthalmic-formulations
#4
Dörte von Deylen, Christina Dreher, Oliver Seidelmann, Stephan Reichl
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. Minimum inhibitory concentrations were determined for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus brasiliensis...
November 8, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30411187/mycobacterium-tuberculosis-and-interactions-with-the-host-immune-system-opportunities-for-nanoparticle-based-immunotherapeutics-and-vaccines
#5
REVIEW
Raymonde B Bekale, Su-Mari Du Plessis, Nai-Jen Hsu, Jyoti R Sharma, Samantha L Sampson, Muazzam Jacobs, Mervin Meyer, Gene D Morse, Admire Dube
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. the Bacillus Calmette-Guerin vaccine, and increasing global antimicrobial resistance, has reinvigorated interest in immunotherapies. Nanoparticles (NPs) potentiate the effect of immune modulating compounds (IMC), enabling cell targeting, improved transfection of antigens, enhanced compound stability and provide opportunities for synergistic action, via delivery of multiple IMCs...
November 8, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30411161/establishment-of-a-mucin-secreting-cell-line-cx-03-from-an-uterine-carcino-sarcoma
#6
R Bücker, C Schaefer, A D Gruber, J Hoppe, L Lazzerini, J Barinoff, J Sehouli, Günter Cichon
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)...
November 8, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30406478/an-expandable-mechanopharmaceutical-device-2-drug-induced-granulomas-maximize-the-cargo-sequestering-capacity-of-macrophages-in-the-liver
#7
Phillip Rzeczycki, Gi Sang Yoon, Rahul K Keswani, Sudha Sud, Jason Baik, Mikhail D Murashov, Ingrid L Bergin, Kathleen A Stringer, Gus R Rosania
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...
November 7, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30406460/pharmaceutical-potential-of-a-novel-chitosan-derivative-schiff-base-with-special-reference-to-antibacterial-anti-biofilm-antioxidant-anti-inflammatory-hemocompatibility-and-cytotoxic-activities
#8
Sameh S Ali, El-Refaie Kenawy, Fatma I Sonbol, Jianzhong Sun, Marwa Al-Etewy, Asmaa Ali, Liu Huizi, Nessma A El-Zawawy
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...
November 7, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30406349/an-overview-of-3d-printing-technologies-for-soft-materials-and-potential-opportunities-for-lipid-based-drug-delivery-systems
#9
REVIEW
Kapilkumar Vithani, Alvaro Goyanes, Vincent Jannin, Abdul W Basit, Simon Gaisford, Ben J Boyd
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...
November 7, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30406281/understanding-the-impacts-of-surface-compositions-on-the-in-vitro-dissolution-and-aerosolization-of-co-spray-dried-composite-powder-formulations-for-inhalation
#10
Sharad Mangal, Rongkun Xu, Heejun Park, Dmitry Zemlyanov, Nivedita Shetty, Yu-Wei Lin, David Morton, Hak-Kim Chan, Jian Li, Qi Tony Zhou
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...
November 7, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30402714/evaluation-of-a-potential-clinical-significant-drug-drug-interaction-between-digoxin-and-bupropion-in-cynomolgus-monkeys
#11
Yang Shen, Yang Yu, Wei Lai, Shuai Li, Zixuan Xu, Jiejing Jin, Xia Yan, Han Xing, Xijing Chen, Aizhen Xiong, Chunhua Xia, Jiake He, Kui Hong
PURPOSE: A three-period digoxin-bupropion drug-drug interaction study was performed in cynomolgus monkeys to assess the effect of bupropion and its metabolites on digoxin disposition. METHODS: Monkeys were administered either an i.v. infusion (0.1 mg/kg) or an oral dose of digoxin (0.2 mg/kg) as control. In single-dosing period, monkeys received an i.v. infusion of bupropion at 1.5 mg/kg together with an infusion or oral dosing of digoxin, respectively. During multiple-dosing period, bupropion was orally administered q...
November 6, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30402713/an-expandable-mechanopharmaceutical-device-3-a-versatile-raman-spectral-cytometry-approach-to-study-the-drug-cargo-capacity-of-individual-macrophages
#12
Vernon LaLone, Márcio A Mourão, Theodore J Standiford, Krishnan Raghavendran, Kerby Shedden, Kathleen A Stringer, Gus R Rosania
PURPOSE: To improve cytometric phenotyping abilities and better understand cell populations with high interindividual variability, a novel Raman-based microanalysis was developed to characterize macrophages on the basis of chemical composition, specifically to measure and characterize intracellular drug distribution and phase separation in relation to endogenous cellular biomolecules. METHODS: The microanalysis was developed for the commercially-available WiTec alpha300R confocal Raman microscope...
November 6, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30397820/a-review-of-the-emerging-role-of-silk-for-the-treatment-of-the-eye
#13
REVIEW
Simon H Tran, Clive G Wilson, F Philipp Seib
Silk is a remarkable biopolymer with a long history of medical use. Silk fabrications have a robust track record for load-bearing applications, including surgical threads and meshes, which are clinically approved for use in humans. The progression of top-down and bottom-up engineering approaches using silk as the basis of a drug delivery or cell-loaded matrix helped to re-ignite interest in this ancient material. This review comprehensively summarises the current applications of silk for tissue engineering and drug delivery, with specific reference to the eye...
November 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30386927/formulating-inhalable-dry-powders-using-two-fluid-and-three-fluid-nozzle-spray-drying
#14
Donglei Leng, Kaushik Thanki, Camilla Foged, Mingshi Yang
PURPOSE: The spray drying process is widely applied for pharmaceutical particle engineering. The purpose of this study was to investigate advantages and disadvantages of two-fluid nozzle and three-fluid nozzle spray drying processes to formulate inhalable dry powders. METHODS: Budesonide nanocomposite microparticles (BNMs) were prepared by co-spray drying of budesonide nanocrystals suspended in an aqueous mannitol solution by using a two-fluid nozzle spray drying process...
November 1, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30374744/topical-drug-delivery-to-the-posterior-segment-of-the-eye-addressing-the-challenge-of-preclinical-to-clinical-translation
#15
REVIEW
Gerard A Rodrigues, David Lutz, Jie Shen, Xiaoda Yuan, Hong Shen, James Cunningham, Hongwen M Rivers
Topical delivery of therapeutics to the posterior segment of the eye remains the "holy grail" of ocular drug delivery. As an example, anti-vascular endothelial growth factor biologics, such as ranibizumab, aflibercept, and bevacizumab, are delivered by intravitreal injection to treat neovascular age-related macular degeneration and, although these drugs have revolutionized treatment of the disease, less invasive alternatives to intravitreal injection are desired. Multiple reports in the literature have demonstrated topical delivery of both small and large molecules to the back of the eye in small animal models...
October 29, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30374619/transport-of-pregabalin-via-l-type-amino-acid-transporter-1-slc7a5-in-human-brain-capillary-endothelial-cell-line
#16
Yu Takahashi, Tomohiro Nishimura, Kei Higuchi, Saki Noguchi, Yuma Tega, Toshiki Kurosawa, Yoshiharu Deguchi, Masatoshi Tomi
PURPOSE: The anti-epileptic drug pregabalin crosses the blood-brain barrier (BBB) in spite of its low lipophilicity. This study was performed to determine whether L-type amino acid transporters (LAT1/SLC7A5 and LAT2/SLC7A8) contribute to the uptake of pregabalin. METHODS: Pregabalin uptake by LATs-transfected HEK293 cells or hCMEC/D3 cells, an in vitro human BBB model, was measured by LC-MS/MS analysis. Expression of LAT1 mRNA in hCMEC/D3 cells was determined by quantitative RT-PCR analysis...
October 29, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30367284/correction-to-application-of-a-novel-make-and-test-in-parallel-strategy-to-investigate-the-effect-of-formulation-on-the-pharmacokinetics-of-gdc-0810-in-healthy-subjects
#17
Sravanthi Cheeti, Hao Helen Hou, Eric Nelson, Helen Walker, Buyun Chen, Roland Morley, Mary Gates, Luna Musib, Sandhya Girish, Srikumar Sahasranaman, Lichuan Liu
The Publisher regrets the typesetting mistake of retaining incorrect text in the Figure 1 caption. The correct text for the caption is "Molecular Structure of GDC-0810 NMG Salt". The original article has been corrected.
October 26, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30361780/irinotecan-alters-the-disposition-of-morphine-via-inhibition-of-organic-cation-transporter-1-oct1-and-2-oct2
#18
Peng Zhu, Zhi Ye, Dong Guo, Zongping Xiong, Shiqiong Huang, Jun Guo, Wei Zhang, James E Polli, Honghao Zhou, Qing Li, Yan Shu
PURPOSE: The organic cation transporters (OCTs) and multidrug and toxin extrusions (MATEs) together are regarded as an organic cation transport system critical to the disposition and response of many organic cationic drugs. Patient response to the analgesic morphine, a characterized substrate for human OCT1, is highly variable. This study was aimed to examine whether there is any organic cation transporter-mediated drug and drug interaction (DDI) between morphine and commonly co-administrated drugs...
October 25, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30349948/the-extended-clearance-concept-following-oral-and-intravenous-dosing-theory-and-critical-analyses
#19
Leslie Z Benet, Christine M Bowman, Shufang Liu, Jasleen K Sodhi
PURPOSE: To derive the theoretical basis for the extended clearance model of organ elimination following both oral and IV dosing, and critically analyze the approaches previously taken. METHODS: We derived from first principles the theoretical basis for the extended clearance concept of organ elimination following both oral and IV dosing and critically analyzed previous approaches. RESULTS: We point out a number of critical characteristics that have either been misinterpreted or not clearly presented in previously published treatments...
October 22, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30338408/editorial-iapc-6-meeting
#20
EDITORIAL
Kin Tam, Tonglei Li, Zoran Mandić
No abstract text is available yet for this article.
October 18, 2018: Pharmaceutical Research
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