title: In vitro evaluation of pH-sensitive cholesterol-containing stable polymeric micelles for delivery of camptothecin.
abstract: Two novel amphiphilic statistical copolymers poly(cholesteryl acrylate-co-methoxypoly(ethylene glycol) methacrylate), poly[CHOL(y)-co-mPEG(n,x)] (for n=5, x=110 and y=15, and for n=23, x=22 and y=3) with copolymer composition (x:y) of 7:1 were designed and synthesized as a delivery system for water-insoluble anticancer agent, S-(+)-camptothecin (CPT). The polymers were synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization technique and they were found to form stable polymeric micelles in water above a relatively low critical concentration. The polymeric micelles (PMs) were characterized by a number of techniques including surface tension, fluorescence, dynamic light scattering, and electron microscopy. Incorporation of CPT into the micelles and the stability of CPT-loaded micelles were studied by spectrophotometric method. Sustained release of an encapsulated fluorescent guest triggered by hydrolysis of the ester linkages in acidic pH is demonstrated. The polymers are not only hemocompatible and nontoxic in the allowed concentration range, but also they can easily permeate into the cancer cells (MCF7 and HeLa). The in vitro drug delivery assay of CPT-loaded polymeric micelles on cancer cells (HeLa) showed very good chemotherapeutic activity in the biocompatible concentration range of the copolymers.
authors: Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India.
authors: Partha
authors: P
authors: Laskar
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur 721 302, India.
authors: Sintu
authors: S
authors: Samanta
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur 721 302, India.
authors: Sudip Kumar
authors: SK
authors: Ghosh
authors: Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India. Electronic address: joydey@chem.iitkgp.ernet.in.
authors: Joykrishna
authors: J
authors: Dey
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002166:Camptothecin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002784:Cholesterol / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D002784:Cholesterol; D002166:Camptothecin
keywords: Camptothecin; Cell permeability; Chemotherapeutic activity; Cytotoxicity; Fluorescence; Hemocompatibility; Polymeric micelle; RAFT; Statistical copolymer; pH-sensitivity