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.

Keywords: Camptothecin; Cell permeability; Chemotherapeutic activity; Cytotoxicity; Fluorescence; Hemocompatibility; Polymeric micelle; RAFT; Statistical copolymer; pH-sensitivity.