Synthesis, self-assembly, and cytotoxicity of well-defined trimethylated chitosan-O-poly(ε-caprolactone): effect of chitosan molecular weight.

Abstract

Structurally well-defined trimethylated chitosan-O-poly(ε-caprolactone) (TMC-O-PCL) was synthesized under mild homogeneous conditions, using sodium dodecyl sulfate-dimethylated chitosan complex (SDC) as an organosoluble intermediate. The effect of chitosan molecular weight (MW) on the preparation, organosolubility, self-assembly, and cytotoxicity of the copolymers was investigated. The copolymers with low-MW chitosan backbone had improved solubility in common organic solvents. Spherical micelles with average diameter of 25-55 nm and uniform morphology were formed through self-assembly of TMC-O-PCL in pH 7.4 PBS. When trimethylation degree of the copolymers was above 44%, the micelles could remain stable in neutral aqueous media. The critical aggregation concentration of TMC-O-PCL slightly increased with a decrease in the MW of chitosan backbone. The cytotoxicity of the cationic micelles could be suppressed by increasing PCL grafting levels, reducing trimethylation degree, and MW of the chitosan backbone.