title: In vivo pharmacokinetic studies and intracellular delivery of methotrexate by means of glycine-tethered PLGA-based polymeric micelles.
abstract: 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.
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan, 305 817, India.
authors.lastname: Madhwi
authors.affiliation: UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University, Chandigarh, 160 014, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan, 305 817, India.
authors.forename: Pramod
authors.initials: P
authors.lastname: Kumar
authors.affiliation: UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University, Chandigarh, 160 014, India; Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies, Panjab University, Chandigarh, 160 014, India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies, Panjab University, Chandigarh, 160 014, India.
authors.forename: Gajanand
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies, Panjab University, Chandigarh, 160 014, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Katare
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan, 305 817, India. Electronic address: drkaisar@curaj.ac.in.
authors.forename: Kaisar
authors.initials: K
authors.lastname: Raza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005998:Glycine / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008727:Methotrexate / Q000737:chemistry* / Q000493:pharmacokinetics*; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005998:Glycine; D008727:Methotrexate
keywords: Bioavailability; Cytotoxicity; Drug delivery; Glycine; MDA-MB-231 cells; Nanoparticles; Protein binding