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In vivo pharmacokinetic studies and intracellular delivery of methotrexate by means of glycine-tethered PLGA-based polymeric micelles

Publication date: 15 March 2017 Source:International Journal of Pharmaceutics, Volume 519, Issues 1–2 Author(s): Madhwi, Rajendra Kumar, Pramod Kumar, Bhupinder Singh, Gajanand Sharma, Om Prakash Katare, Kaisar Raza Methotrexate (MTX) is a widely used drug for the management of various kinds of cancers. However, numerous challenges are associated with MTX like poor aqueous solubility, dose-dependent side effects and poor-bioavailability. With an aim to explore the potential benefits in drug delivery of MTX, it was intended to fabricate glycine-PLGA-based polymeric micelles. Glycine was chemically linked to PLGA and the linkage was confirmed by FT-IR, and NMR-Spectroscopy. The developed polymeric micelles offered substantial loading to MTX with a pH-dependent drug release profile. The drug was released maximally at the cancer cell pH vis-à-vis blood plasma pH. The cytotoxicity of drug against MDA-MB-231 cell lines was enhanced by approx. 100% and the confocal laser scanning microscopy confirmed the localization of dye-tagged nanocarriers in the interiors of cancer cells. The bioavailable fraction of the drug was increased by approx. 4-folds, whereas elimination half-life was enhanced by around two-folds in Wistar rats. The novel approach offers a biodegradable and promising carrier for the better delivery of anticancer agents with immense promises of efficacy enhancement, improved delivery and better pharmacokinetic profile. Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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Source: Pancreas - Category: Gastroenterology Tags: Original Articles Source Type: research
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Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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