Formation of thermo-sensitive polyelectrolyte complex micelles from two biocompatible graft copolymers for drug delivery

Thermo-sensitive polyelectrolyte complex (PEC) micelles assembled from two biocompatible graft copolymers chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAM) and carboxymethyl cellulose-g-poly(N-isopropylacrylamide) (CMC-g-PNIPAM) were prepared for delivery of 5-fluorouracil (5-FU). The PEC micelles showed a narrow size distribution with core-shell structure, in which the core formed from positively charged CS and negatively charged CMC by electrostatic interactions and the shell formed from thermo-sensitive PNIPAM. The synthesized PEC micelles have lower critical solution temperatures (LCST) in the region of 37 degrees C, which is favorable for smart drug delivery applications. The hydrogen bondings between PEC micelles and 5-FU increased the drug loading. Changing temperature, pH or ionic strength, a sustained and controlled release was observed due to the deformation of PEC micelles. Adding glutaraldehyde, a chemical crosslinking reagent, was an efficient way to reinforce the micelles structure and decrease the initial burst release. Cytotoxicity assays showed that drug-loaded PEC micelles retained higher cell inhibition efficiency in HeLa cells. (C) 2013 Wiley Periodicals, Inc.