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°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.