In Vitro and In Vivo Evaluation of Novel Implantable Collagen-Chitosan-Soybean Phosphatidylcholine Composite Film for the Sustained Delivery of Mitomycin C

An implantable mitomycin C (MMC) delivery system (MMC-film), incorporating polylactide (PLA)–MMC nanoparticles in a composite film from blends of collagen–chitosan–soybean phosphatidylcholine (SPC) with a mass ratio of 4:1:1, was developed and evaluated. PLA–MMC nanoparticles were prepared using an improved emulsion/solvent evaporation technique and then dispersed uniformly within the film to result in a final MMC loading content of 0.8 mg/cm2. Drug release studies were performed in pH 7.4 PBS at 37°C with drug analysis using UV/vis spectrometer at 366 nm. The MMC-film exhibited more fractional drug release and a longer time to reach release equilibrium as compared with PLA-MMC nanoparticles. In vivo, the MMC-film was implanted at subcutaneous tumor sites of hepatoma-bearing mice, and the curative effect was compared with those of drug-free film. The growth of the tumors was dose-dependently inhibited by MMC-film. Histopathological analysis of specimens taken from tumor tissues harvested indicated that MMC-film was lethal to hepatoma cells. Additionally, post mortem visual examination and microscopic images showed no sign of internal infection and fibrous encapsulation in any animals after 20 days of implantation of the MMC-film or drug-free film. It was concluded that the system provides great potential for local sustained delivery of MMC at the site of tumor or tumor resection for therapeutic purposes. Drug Dev Res 2009. © 2009 Wiley-Liss, Inc.