| Cancer is a great threat to the health of human beings. At present, chemical therapy is a commom method of its treatment comparing with operation and radial therapy. Although the traditional intravenous chemotherapy has a certain effect, it's often difficult for patients to tolerance because of severe side effects all over the body. In recent years, great success has been made for interstitial chemotherapy using controlled or sustained release drug delivery system. Interstitial chemotherapy has become an effective method of local chemotherapy.Mitomycin C (MMC) is a broad-spectrum antitumor antibiotic drug. Form of medication is freeze-dried powder injection. To reduce the amount of administration and side effects, MMC-loaded nanoparticles were first prepared with reverse micellar emulsion-solvent evaporation method, and the composite film and drug-loaded film were further prepared. Then, we investigated the in vivo pharmacodynamic effects and biocompatibility of drug-loaded film through animal experiments. The contents are summarized as follows:1. Preparation, optimization and properties of MMC-loaded nanoparticles: MMC-loaded nanoparticles were prepared with novel reverse micellar emulsion-solvent evaporation method, and preparation techniques were optimized through orthogonal design. Properties of MMC-loaded nanoparticles (eg. morphological form, diameter, distribution, Zeta electric potential, drug loading, encapsulation efficiency, in vitro release properties) and drug distribution in phytosome and nanoparticles were investigated in this thesis. The results showed that the nanoparticles produced with the optimized recipes and preparation technique displayed smooth surface, consistent diameters, mean diameter controlled between 300-800 nm, the max encapsulation efficiency more than 90%, and obvious sustained-release effect in vitro release period.2. Prepration and properties of composite film and MMC-loaded film: Collagen, chitosan, and soybean phosphatidylcholine were chosen as film materials. Composite film and MMC-loaded film were prepared and their properties (eg. morphological form, swelling ratio, the interaction among film materials, in vitro releasing curve) were investigated. The results showed that composite film and MMC-loaded film had favourable microstructure and nanoparticles were uniformly distributed over internal and surface of film; swelling ratios of composite film and MMC-loaded film were obvious reduced compared with collagen film; the excellent biological characteristics of collagen had been retained in composite film; the in vitro release rate of MMC-loaded film was slower and more stable than MMC-loaded nanoparticles, and displayed favourable sustained-release effect with no burst release.3. The in vivo pharmacodynamic effect and biocompatibility study: The inhibition effect of MMC-loaded film on H22 solid tumor developed in mice was investigated through interstitial chemotherapy with film implanting around tumor, and the biocompatibility of MMC-loaded film was evaluated with pathological examination of mice skin after implantation. The results suggested that the inhibition effect of MMC-loaded film was obvious and dose-dependent and higher than that of MMC injection. Besides, MMC-loaded film could remarkably reduce side effects of MMC. Through pathological examination, it could be inferred that MMC-loaded film had lethal effect to hepatoma carcinoma cell because of its functions with inhibiting tumor cells increase and leading its apoptosis. Inflammation response in mice skin could be observed after implantation of MMC-loaded film, but no sign of infiltration liquid accumulation was found, and neither did of obvious angiogenesis and fiber hyperplasia. So it implied that MMC-loaded film possessed good biological compatibility.
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