title: Dextran-PLGA-loaded docetaxel micelles with enhanced cytotoxicity and better pharmacokinetic profile.
abstract: Docetaxel is one of the promising drugs and employed for the management of variety of cancers. However, challenges like poor-bioavailability, low tissue-permeability, compromised aqueous solubility and dose-dependent side-effects limit its clinical applications. Whereas, PLGA-based polymeric micelles possess the ability to enhance the tissue permeability of drugs and increase their biocompatibility. Henceforth, it was aimed to fabricate the dextran-PLGA-based polymeric-micelles loaded with docetaxel to explore the potential benefits in drug delivery. Dextran was chemically linked to PLGA and the linkage was confirmed by FT-IR, UV and NMR-spectroscopy. Critical-micelle-concentration of amphiphilic polymer was determined and drug was encapsulated by diffusion technique and erythrocyte compatibility. The system was evaluated for drug release profile and in vitro cytotoxicity studies. The pharmacokinetic profile was studied in rats. The micelles obtained were of 96.5±2.5nm and offered drug encapsulation of order of 54.85±1.21%.The cytotoxicity of drug against MCF-7 and MDA-MB-231 cell lines was enhanced by approx. 100%. The pharmacokinetic profile was substantially modified and about 16-folds enhancement in bioavailability was observed vis-à-vis plain drug. The approach was not only able to control the drug release, but also offered promise to enhance the pharmacokinetic and pharmacodynamic potential of docetaxel and similar anticancer agents.
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan 305817, India. Electronic address: drkaisar@curaj.ac.in.
authors.forename: Kaisar
authors.initials: K
authors.lastname: Raza
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan 305817, India.
authors.forename: Nitesh
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan 305817, India.
authors.forename: Charu
authors.initials: C
authors.lastname: Misra
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan 305817, India.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Kaushik
authors.affiliation: Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Guru
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan 305817, India.
authors.forename: Pramod
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan 305817, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Malik
authors.affiliation: Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: O P
authors.initials: OP
authors.lastname: Katare
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry*; D000077143:Docetaxel; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D004912:Erythrocytes; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D004337:Drug Carriers; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Biomacromolecule; Cytotoxicity; Drug release