The Study Of Collagen-Chitosan Complex Film Containing VCR-microspheres

Cancer chemotherapy is not always effective. Difficulties in drug delivery to the tumor site, drug toxicity to normal tissues, and drug stability in the body contribute to this problem. The production and characterization of implant films made of collagen, chitosan and PLGA microspheres for the delivery of VCR is described. The objective of this study is to investigate the film and their characters. A water-in-oil-in-oil double-emulsion/solvent evaporation method was used to prepare VCR-loaded PLGA microspheres, with ZnCO3 suspended in the polymer solution as additive to raise the microclimate pH inside the microspheres. Then microspheres were mixed withcollagen and (or) chitosan swelling solution, and lyophilized. The films were cross-linked by 0.3% glutaraldehyde. Encapsulation efficiency, particle size and release kinetics of VCR microspheres were fully characterized, as well as in vitro degradation and release kinetics of the film. The rate of VCR release from the film submerged in PBS (pH6.8) and the content were measured by high-performance liquid chromatography (HPLC). We also observed the physical & chemical properties of the film such as surface morphology, mechanical function, differential scanning calorimetry. All data were analyzed using ANOVA.The neutralization of acidic PLGA microclimate by addding ZnCO₃ reduced degradation of the VCR evidently. VCR was released from the film in a prolonged period and the initial burst release of the film was less significant than the microspheres. The initial release of microspheres is (27.3±1.2)%, but as for the film of collagan and collagen- chitosan(9:1, 4:1, 3:2, w/w) it is(20.3±1.2)%,(18.2±1.0)%, (16.6±1.6)% respectively. In vitro degradation experiment, the film containing chitosan degraded more slowly than that without chitosan. The chitosan-free collagen film is loosen after 2 weeks during the release period, and microspheres were fewer than ever. With more proportion of chitosan, the tensile strength of the film was strenghened, and the breaking elongating rate of the film was decreased. DSC thermogram of the collagan film suggested that more degradation product than that of the film with chitosan. The results suggest that chitosan could significantly affect physical & chemical properties of the film, especially the degradation rate and initial burst release of VCR. The film (collagen:chitosan 4:1) is properly. Preparation stability testing suggest that the film should store under a dried place and keep away from light.In conclusion, the film could achieve the goal of a relative constant release of drug and the initial burst release was decreased to some extent. It has a prospect future.