Preparation of polysaccharide derivates chitosan-graft-poly(ɛ-caprolactone) amphiphilic copolymer micelles for 5-fluorouracil drug delivery.

Biodegradable graft copolymer, chitosan-graft-poly(ɛ-caprolactone) (CS-g-PCL) was synthesized via ring opening polymerization and characterized by (1)H NMR and FTIR spectroscopy. Then graft copolymers were self-assembled into micelles as drug delivery system. To evaluate drug-polymer compatibility, the Flory-Huggins interaction parameter between 5-fluorouraci (5-Fu) and hydrophobic segment was calculated. The result was in agreement with experimental data from drug loading content and drug loading efficiency. Meanwhile, DLS and TEM were utilized to evaluate the trend of particle size and morphology in aqueous solution with different repeating units of ɛ-CL. The in vitro drug release data was fitted with three kinetic models, usually applied in the drug delivery system. Results indicated that the release of 5-Fu was controllable and the release half-time could reach as long as 54.46 h, much slower than that of free 5-Fu. Cytotoxicity evaluation and cellular apoptosis study suggested good biocompatibility of CS-g-PCL micelles. Moreover, 5-Fu loaded micelles could delay the release of drug and exert comparable cytotoxicity against A549 cells.