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Pharmaceutical Research

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https://www.readbyqxmd.com/read/28646325/anti-tuberculosis-bacteriophage-d29-delivery-with-a-vibrating-mesh-nebulizer-jet-nebulizer-and-soft-mist-inhaler
#1
Nicholas B Carrigy, Rachel Y Chang, Sharon S Y Leung, Melissa Harrison, Zaritza Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hak-Kim Chan, Dominic Sauvageau, Warren H Finlay, Reinhard Vehring
PURPOSE: To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices. METHODS: Phage D29 lysate was amplified to a titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify phage titer...
June 23, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28646324/expression-purification-and-characterization-of-gmz2-10c-a-complex-disulphide-bonded-fusion-protein-vaccine-candidate-against-the-asexual-and-sexual-life-stages-of-the-malaria-causing-plasmodium-falciparum-parasite
#2
Ulrik H Mistarz, Susheel K Singh, Tam T T N Nguyen, Will Roeffen, Fen Yang, Casper Lissau, Søren M Madsen, Astrid Vrang, Régis W Tiendrebeogo, Ikhlaq H Kana, Robert W Sauerwein, Michael Theisen, Kasper D Rand
PURPOSE: Production and characterization of a chimeric fusion protein (GMZ2'.10C) which combines epitopes of key malaria parasite antigens: glutamate-rich protein (GLURP), merozoite surface protein 3 (MSP3), and the highly disulphide bonded Pfs48/45 (10C). GMZ2'.10C is a potential candidate for a multi-stage malaria vaccine that targets both transmission and asexual life-cycle stages of the parasite. METHODS: GMZ2'.10C was produced in Lactococcus lactis and purified using either an immunoaffinity purification (IP) or a conventional purification (CP) method...
June 23, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28643237/small-airway-absorption-and-microdosimetry-of-inhaled-corticosteroid-particles-after-deposition
#3
P Worth Longest, Michael Hindle
PURPOSE: To predict the cellular-level epithelial absorbed dose from deposited inhaled corticosteroid (ICS) particles in a model of an expanding and contracting small airway segment for different particle forms. METHODS: A computational fluid dynamics (CFD)-based model of drug dissolution, absorption and clearance occurring in the surface liquid of a representative small airway generation (G13) was developed and used to evaluate epithelial dose for the same deposited drug mass of conventional microparticles, nanoaggregates and a true nanoaerosol...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28643236/multi-reservoir-phospholipid-shell-encapsulating-protamine-nanocapsules-for-co-delivery-of-letrozole-and-celecoxib-in-breast-cancer-therapy
#4
Ahmed O Elzoghby, Shaimaa K Mostafa, Maged W Helmy, Maha A ElDemellawy, Salah A Sheweita
PURPOSE: In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). METHODS: Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. RESULTS: Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28643235/design-and-evaluation-of-rgd-modified-gemini-surfactant-based-lipoplexes-for-targeted-gene-therapy-in-melanoma-model
#5
Waleed Mohammed-Saeid, Jackson Chitanda, Mays Al-Dulaymi, Ronald Verrall, Ildiko Badea
PURPOSE: We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy. METHODS: Integrin receptor targeting peptide, cyclic-arginylglycylaspartic acid (cRGD), was either chemically coupled to a gemini surfactant backbone or physically co-formulated with lipoplexes. Several formulations and transfection techniques were developed. Transfection efficiency and cellular toxicity of the lipoplexes were evaluated in an in vitro human melanoma model...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28639052/gentamicin-loaded-polysaccharide-membranes-for-prevention-and-treatment-of-post-operative-wound-infections-in-the-skeletal-system
#6
Urszula Cibor, Małgorzata Krok-Borkowicz, Monika Brzychczy-Włoch, Łucja Rumian, Krzysztof Pietryga, Dominika Kulig, Wojciech Chrzanowski, Elżbieta Pamuła
PURPOSE: To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections. METHODS: Membranes made of gellan gum (GUM), sodium alginate (ALG), GUM and ALG crosslinked with calcium ions (GUM + Ca and ALG + Ca, respectively) as well as reference collagen (COL) were produced by freeze-drying. Mechanical properties, drug release, antimicrobial activity and cytocompatibility of the membranes were assessed...
June 21, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28631206/diclofenac-loaded-lipid-nanovesicles-prepared-by-double-solvent-displacement-for-skin-drug-delivery
#7
M Sala, F Locher, M Bonvallet, G Agusti, A Elaissari, H Fessi
PURPOSE: Herein, we detail a promising strategy of nanovesicle preparation based on control of phospholipid self-assembly: the Double Solvent Displacement. A systematic study was conducted and diclofenac as drug model encapsulated. In vitro skin studies were carried out to identify better formulation for dermal/transdermal delivery. METHODS: This method consists in two solvent displacements. The first one, made in a free water environment, has allowed triggering a phospholipid pre-organization...
June 19, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28623473/increasing-the-bile-acid-sequestration-performance-of-cationic-hydrogels-by-using-an-advanced-controlled-polymerization-technique
#8
Patrícia V Mendonça, André Matos, Andreia F Sousa, Arménio C Serra, Sérgio Simões, Jorge F J Coelho
PURPOSE: To investigate the influence of the polymerization technique and the content of hydroxyl groups on the performance of new bile acid sequestrants based on PAMPMTA-co-PHEA (PAMPTMA: poly((3-acrylamidopropyl)trimethylammonium chloride); PHEA: poly(2-hydroxyethyl acrylate)) hydrogels. METHODS: PAMPMTA-co-PHEA hydrogels were prepared using either free radical polymerization or supplemental activator and reducing agent atom transfer radical polymerization. The chemical structure and composition of the hydrogels was confirmed by both FTIR and ssNMR...
June 16, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28620888/design-of-isoniazid-smart-nanogel-by-gamma-radiation-induced-template-polymerization-for-biomedical-application
#9
Samia M Omar, Nabila A Maziad, Nourhan M El-Tantawy
PURPOSE: Preparation of Isoniazid (INH) loaded nanogel particles using gamma radiation as safe, simple, cheap and reproducible technique for promoting mycobacterial killing in a lower-dose system aiming in developing of drug resistance. METHODS: Polymeric pH-sensitive nanogels were prepared by gamma radiation-induced polymerization of Acrylic acid (AAc) or Itaconic acid (IA), in aqueous solution of polyvinylpyrrolidone (PVP), as template polymer. The prepared nanogels were utilized for encapsulation of INH...
June 15, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28620887/controlled-suspensions-enable-rapid-determinations-of-intrinsic-dissolution-rate-and-apparent-solubility-of-poorly-water-soluble-compounds
#10
Sara B E Andersson, Caroline Alvebratt, Christel A S Bergström
PURPOSE: To develop a small-scale set-up to rapidly and accurately determine the intrinsic dissolution rate (IDR) and apparent solubility of poorly water-soluble compounds. METHODS: The IDR and apparent solubility (Sapp) were measured in fasted state simulated intestinal fluid (FaSSIF) for six model compounds using wet-milled controlled suspensions (1.0% (w/w) PVP and 0.2% (w/w) SDS) and the μDISS Profiler. Particle size distribution was measured using a Zetasizer and the total surface area was calculated making use of the density of the compound...
June 15, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28616685/endocytic-uptake-transport-and-macromolecular-interactions-of-anionic-pamam-dendrimers-within-lung-tissue
#11
Christopher J Morris, Ghaith Aljayyoussi, Omar Mansour, Peter Griffiths, Mark Gumbleton
PURPOSE: Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. METHODS: Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy...
June 14, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28616684/influence-of-ethanol-on-darunavir-hepatic-clearance-and-intracellular-pk-pd-in-hiv-infected-monocytes-and-cyp3a4-darunavir-interactions-using-inhibition-and-in-silico-binding-studies
#12
Narasimha M Midde, Yuqing Gong, Theodore J Cory, Junhao Li, Bernd Meibohm, Weihua Li, Santosh Kumar
PURPOSE: Although the prevalence of alcohol consumption is higher in HIV+ people than general public, limited information is available on how alcohol affects the metabolism and bioavailability of darunavir (DRV). METHODS: DRV was quantified by using LC-MS/MS method. All in vitro experiments were performed using human liver microsomes and HIV-infected monocytic cells. CYP3A4 and DRV/Ritonavir (RTV) docking was performed using GOLD suite 5.8. RESULTS: Ethanol (20 mM) significantly decreased apparent half-life and increased degradation rate constant of RTV-boosted DRV but not for DRV alone...
June 14, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28608140/on-the-road-to-development-of-an-in-vitro-permeation-test-ivpt-model-to-compare-heat-effects-on-transdermal-delivery-systems-exploratory-studies-with-nicotine-and-fentanyl
#13
Soo Hyeon Shin, Priyanka Ghosh, Bryan Newman, Dana C Hammell, Sam G Raney, Hazem E Hassan, Audra L Stinchcomb
PURPOSE: At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). METHODS: IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs...
June 12, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28608139/doxorubicin-hydrochloride-loaded-zymosan-polyethylenimine-biopolymeric-nanoparticles-for-dual-chemoimmunotherapeutic-intervention-in-breast-cancer
#14
Vivek K Pawar, Yuvraj Singh, Komal Sharma, Arpita Shrivastav, Abhisheak Sharma, Akhilesh Singh, Jaya Gopal Meher, Pankaj Singh, Kavit Raval, Himangshu K Bora, Dipak Datta, Jawahar Lal, Manish K Chourasia
OBJECTIVE: To utilize nanoparticles produced by condensation of zymosan (an immunotherapeutic polysaccharide) with pegylated polyethylenimine (PEG-PEI) for dual intervention in breast cancer by modulating tumor microenvironment and direct chemotherapy. METHOD: Positively charged PEG-PEI and negatively charged sulphated zymosan were utilized for electrostatic complexation of chemoimmunotherapeutic nanoparticles (ChiNPs). ChiNPs were loaded with doxorubicin hydrochloride (DOX) for improved delivery at tumor site and were tested for in-vivo tolerability...
June 12, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28608138/a-functional-iron-oxide-nanoparticles-modified-with-pla-peg-dg-as-tumor-targeted-mri-contrast-agent
#15
Fei Xiong, Ke Hu, Haoli Yu, Lijun Zhou, Lina Song, Yu Zhang, Xiuhong Shan, Jianping Liu, Ning Gu
PURPOSE: Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent. METHODS: In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe3O4@OA NPs...
June 12, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28593474/high-throughput-prediction-approach-for-monoclonal-antibody-aggregation-at-high-concentration
#16
Mitja Zidar, Ana Šušterič, Miha Ravnik, Drago Kuzman
PURPOSE: Characterization of the monoclonal antibody aggregation process and identification of stability factors that could be used as indicators of aggregation propensity with an emphasis on a large number of samples and low protein material consumption. METHODS: Differential scanning calorimetry, dynamic light scattering and size exclusion chromatography were used as the main methodological approaches. Conformational stability, colloidal stability and aggregation kinetics were assessed for two different IgG monoclonal antibody (mAbs) subclasses...
June 7, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28593473/pharmacokinetic-pharmacodynamic-relationship-of-erenumab-amg-334-and-capsaicin-induced-dermal-blood-flow-in-healthy-and-migraine-subjects
#17
Thuy Vu, Peiming Ma, Jiyun Sunny Chen, Jan de Hoon, Anne Van Hecken, Lucy Yan, Liviawati Sutjandra Wu, Lisa Hamilton, Gabriel Vargas
PURPOSE: Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. METHODS: Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined...
June 7, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28589445/chemoprevention-of-breast-cancer-by-transdermal-delivery-of-%C3%AE-santalol-through-breast-skin-and-mammary-papilla-nipple
#18
Kaushalkumar Dave, Fahd M Alsharif, Saiful Islam, Chandradhar Dwivedi, Omathanu Perumal
PURPOSE: Almost all breast cancers originate from epithelial cells lining the milk ducts in the breast. To this end, the study investigated the feasibility of localized transdermal delivery of α-santalol, a natural chemopreventive agent to the breast. METHODS: Different α-santalol formulations (cream, solution and microemulsion) were developed and the in vitro permeability was studied using excised animal (porcine and rat) and human breast skin/mammary papilla (nipple)...
June 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28589444/reflections-on-the-future-of-pharmaceutical-public-private-partnerships-from-input-to-impact
#19
REVIEW
Remco L A de Vrueh, Daan J A Crommelin
Public Private Partnerships (PPPs) are multiple stakeholder partnerships designed to improve research efficacy. We focus on PPPs in the biomedical/pharmaceutical field, which emerged as a logical result of the open innovation model. Originally, a typical PPP was based on an academic and an industrial pillar, with governmental or other third party funding as an incentive. Over time, other players joined in, often health foundations, patient organizations, and regulatory scientists. This review discusses reasons for initiating a PPP, focusing on precompetitive research...
June 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28589443/metformin-a-future-therapy-for-neurodegenerative-diseases
#20
REVIEW
Magdalena Markowicz-Piasecka, Joanna Sikora, Aleksandra Szydłowska, Agata Skupień, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties...
June 6, 2017: Pharmaceutical Research
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