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Drug release

Mousumi Pal, Utpal Nandi, Debaraj Mukherjee
Ruthenium (Ru) complexes are known for their promising anticancer activity presumably due to octahedral coordination geometry, slow ligand exchange rate, the range of different oxidation states and target specificity. This review article summarizes the physicochemical processes which are responsible for the selectivity of Ru complexes toward cancer cells over the normal cells. Emphasis has been given on the activation mechanism of Ru(III) complex administered as a prodrug and then the release of active species in an acidic environment of cancer cell through normal or photo induced hydrolysis or ligand oxidation...
March 7, 2018: European Journal of Medicinal Chemistry
Luis Anel-López, Olga Garcia-Álvarez, Tatiana Tarantini, David Del Olmo, Jose Antonio Ortiz, Sergio Ledda, Emilio Arsenio Martinez, Ana J Soler, Jordi Roca, María R Fernández Santos, Juan Maria Vázquez, Inmaculada Parrilla, Jose Julián Garde
The aim of this study was to assess the effect of insemination timing on pregnancy rates in red deer (Cervus elaphus) when using sex-sorted sperm samples. Semen was collected by electroejaculation from 8 mature stags and processed to obtain: Conventional samples, following standard freezing procedures for commercial purposes; Control sorted samples, diluted and handled as per sorted samples but without being submitted to the sorter passage; and Y Sex Sorted (YSS) samples. Hinds were synchronized via intravaginal CIDR (Controlled Internal Drug Release) placement and given eCG (Folligon® PMSG Serum Gonadotrophin) on day 12, upon CIDR removal...
March 9, 2018: Theriogenology
Poovizhi Ponnammal, Parijat Kanaujia, Yin Yani, Wai Kiong Ng, Reginald B H Tan
In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w / w . Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form...
March 16, 2018: Pharmaceutics
Kyle I Mentkowski, Jonathan D Snitzer, Sarah Rusnak, Jennifer K Lang
Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease...
March 15, 2018: AAPS Journal
Lisa Menegazzo, Valentina Scattolini, Roberta Cappellari, Benedetta Maria Bonora, Mattia Albiero, Mario Bortolozzi, Filippo Romanato, Giulio Ceolotto, Saula Vigili de Kreutzeberg, Angelo Avogaro, Gian Paolo Fadini
AIMS: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis. METHODS: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months. To control for the effect on glucose, we also measured NET components in the plasma of patients with type 2 diabetes before and after treatment with insulin or dapagliflozin...
March 15, 2018: Acta Diabetologica
Beatriz V R Pereira, Gregorio Nolazco Matus, Monica Jones Costa, André Cordeiro Alves Dos Santos, Elaine C M Silva-Zacarin, Janaina Braga do Carmo, Bruno Nunes
Over time, many pollutants of anthropogenic origin have caused the contamination of aquatic ecosystems. Among several characteristics, these compounds can reach the trophic chain, causing deleterious interactions with the biota. Pharmaceutical substances can be included in this scenario as emerging contaminants that reach the aquatic environment because of direct human and veterinary usage, and release by industrial effluents, as well as through domestic dumping of surplus drugs. The effects of these compounds on exposed organisms have been studied since the 1990s, but ecotoxicological data for such chemicals are still scarce especially concerning aquatic organisms from tropical regions...
March 15, 2018: Environmental Science and Pollution Research International
Oliver D Montagnat, Graham R Webster, Jürgen B Bulitta, Cornelia Landersdorfer, Rosemary Wyber, Meru Sheel, Jonathan R Carapetis, Ben J Boyd
Jürgen B. Bulitta's name was misspelled in the original version of the article. It is correct as reflected here. The original article has been revised.
March 15, 2018: Drug Delivery and Translational Research
Yuan-Jun Xia, Hong Xia, Ling Chen, Qing-Shui Ying, Xiang Yu, Li-Hua Li, Jian-Hua Wang, Ying Zhang
Bone morphogenetic protein-2 (BMP-2) serves an important role in the development of bone and cartilage. However, administration of BMP-2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP-2 by carriers has been proven necessary to improve the osteogenesis effect of BMP-2. The present study constructed a novel drug delivery system using dextran sulfate (DS)-chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP-2)...
April 2018: Experimental and Therapeutic Medicine
Dan-Dan Wang, Qing-Xi Wu, Wen-Juan Pan, Sajid Hussain, Shomaila Mehmood, Yan Chen
Background: Polysaccharides extracted from fungus that have been used widely in the food and drugs industries due to biological activities. Objective: The objective of the present study was to investigate the tumor-suppressive activity and mechanism of a novel polysaccharide (SAP) extracted from Sarcodon aspratus . Methods: The SAP was extracted and purified using Sepharose CL-4B gel from S. aspratus . The cytotoxicity of SAP on cell lines was determined by MTT method...
2018: Food & Nutrition Research
Marwa M Abu-Serie
Liver cancer is mainly originated by cancer stem cells (CSCs). Due to difference in pH between normal and tumor cell microenvironments, targeting hepatic CSCs exploiting pH-dependent charge switchable nanoparticles (NPs) is extremely required to limit nonselective toxicity to normal hepatocytes (NHCs) and to completely eliminate the root of cancer origin. In this study, NPs were prepared from cationic chitosan and then coated with anionic albumin namely uncoated and coated NPs, respectively. Both NPs were loaded with diethyldithiocarbamate (DDC) which is an inhibitor of the critical enzyme, aldehyde dehydrogenase (ALDH) 1A1, for CSCs survival...
March 15, 2018: Scientific Reports
James W Hindley, Yuval Elani, Catriona M McGilvery, Simak Ali, Charlotte L Bevan, Robert V Law, Oscar Ces
Cell-sized vesicles have tremendous potential both as miniaturised pL reaction vessels and in bottom-up synthetic biology as chassis for artificial cells. In both these areas the introduction of light-responsive modules affords increased functionality, for example, to initiate enzymatic reactions in the vesicle interior with spatiotemporal control. Here we report a system composed of nested vesicles where the inner compartments act as phototransducers, responding to ultraviolet irradiation through diacetylene polymerisation-induced pore formation to initiate enzymatic reactions...
March 15, 2018: Nature Communications
Danuta Jarocha, Karen K Vo, Randolph B Lyde, Vincent Hayes, Rodney M Camire, Mortimer Poncz
In vitro-grown megakaryocytes for generating platelets may have value in meeting the increasing demand for platelet transfusions. Remaining challenges have included the poor yield and quality of in vitro-generated platelets. We have shown that infusing megakaryocytes leads to intrapulmonary release of functional platelets. A Src kinase inhibitor (SU6656), a Rho-associated kinase inhibitor (Y27632), and an aurora B kinase inhibitor (AZD1152) have been shown to increase megakaryocyte ploidy and in vitro proplatelet release...
March 27, 2018: Blood Advances
Hao Chen, Yueyue Chen, Han Wu, Jiang-Fei Xu, Zhiwei Sun, Xi Zhang
We develop a strategy of supramolecular polymeric chemotherapy based on a new kind of water-soluble polymer that bears cucurbit[7]uril (CB[7]) in the main-chain. To this end, we synthesized a bis-alkynyl functionalized CB[7] and polymerized it with α,ω-diazide-PEG through click reaction to form the desired CB[7] based main-chain polymer (poly-CB[7]). Anticancer drug, oxaliplatin, could be encapsulated into the cavity of poly-CB[7] to form a supramolecular polymeric complex, which displayed low cytotoxicity to normal cells...
February 28, 2018: Biomaterials
Sandrina Lampis, Maura Carboni, Daniela Steri, Sergio Murgia, Maura Monduzzi
Lipid based formulations, endowed of long term stability as a result of the formation of lamellar liquid crystals, were prepared using the natural lipids lecithin and glycerol trioleate in water, and characterized using optical microscopy, SAXRD and NMR. The formulations, designed as possible carriers for lysozyme and caffeine, were evaluated for structural features and stability after the loading of the guest molecules. Release experiments were performed at 37 °C using the PBS medium. No burst release was observed either for lysozyme or caffeine...
March 2, 2018: Colloids and Surfaces. B, Biointerfaces
Urmi Bajpai, Abhishek Kumar Mehta, Kandasamy Eniyan, Avni Sinha, Ankita Ray, Simran Virdi, Shazeb Ahmad, Aridni Shah, Deepanksha Arora, Devyani Marwaha, Gunjan Chauhan, Prarthna Saraswat, Punita Bathla, Ruchi Singh
Bacteriophages are being considered as a promising natural resource for the development of alternative strategies against mycobacterial diseases, especially in the context of the wide spread occurrence of drug-resistance amongst the clinical isolates of M. tuberculosis. However, there isn't much information documented on mycobacteriophages from India. Here, we report the isolation of 17 mycobacteriophages using M. smegmatis as the bacterial host where 9 phages also lyse M. tuberculosis H37Rv. We present detailed analysis of one of these mycobacteriophage (PDRPv)...
March 15, 2018: Canadian Journal of Microbiology
Grace Juyun Kim, Kye Hwa Lee, Ju Han Kim
BACKGROUND: The Beers Criteria released by the American Geriatrics Society includes a list of drugs to avoid in the geriatric population and is frequently used as a safety resource in geriatric pharmacotherapy. OBJECTIVE: To evaluate the exposure of South Korean geriatrics to potentially inappropriate medications according to the Beers Criteria and the risk of adverse events from these medications. METHODS: This study included medications recommended to be avoided in patients 65 years or older regardless of concomitant drug therapy or disease...
2018: PloS One
Leslee Sprague, Joel M Lee, Brian J Hutzen, Pin-Yi Wang, Chun-Yu Chen, Joe Conner, Lynne Braidwood, Kevin A Cassady, Timothy P Cripe
High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, other groups including previous reports from our laboratory highlight the synergistic effects of OVs with chemotherapy drugs. Here, we show that virus-free supernatants have varying cytotoxic potential, and HMGB1 is actively secreted by two established fibroblast cell lines (NIH 3T3 and 3T6-Swiss albino) following HSV1716 infection in vitro...
March 15, 2018: Viruses
Nora Freyer, Selina Greuel, Fanny Knöspel, Florian Gerstmann, Lisa Storch, Georg Damm, Daniel Seehofer, Jennifer Foster Harris, Rashi Iyer, Frank Schubert, Katrin Zeilinger
The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0...
March 15, 2018: Bioengineering
Petr Chytil, Milada Sirova, Júlia Kudláčová, Blanka Rihova, Karel Ulbrich, Tomáš Etrych
Herein, the biodegradable micelle-forming amphiphilic N-(2-hydroxypropyl) methacrylamide (HPMA)-based polymer conjugates with the anti-cancer drug doxorubicin (Dox) designed for enhanced tumor accumulation were investigated, and the influence of their stability in the blood stream on biodistribution, namely, tumor uptake, and in vivo antitumor efficacy were evaluated in detail. Dox was attached to the polymer carrier by a hydrazone bond enabling pH-controlled drug release. While the polymer-drug conjugates were stable in a buffer at pH 7...
March 15, 2018: Molecular Pharmaceutics
Kuikun Yang, Yijing Liu, Yi Liu, Qian Zhang, Chuncai Kong, Chenglin Yi, Zijian Zhou, Zhantong Wang, Guofeng Zhang, Yang Zhang, Niveen M Khashab, Xiaoyuan Chen, Zhihong Nie
This article describes the fabrication of nanosized magneto-vesicles (MVs) comprising tunable layers of densely-packed superparamagnetic iron oxide nanoparticles (SPIONs) in membranes via cooperative assembly of polymer-tethered SPIONs and free poly(styrene)-b-poly(acrylic acid) (PS-b-PAA). The membrane thickness of MVs could be well controlled from 9.8 to 93.2 nm by varying the weight ratio of PS-b-PAA to SPIONs. The increase in membrane thickness was accompanied with the transition from monolayer MVs, to double-layered MVs and to multilayered MVs (MuMVs)...
March 15, 2018: Journal of the American Chemical Society
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