| MitomycinC-polybutylcyanoacrylate-nanoparticles(MMC-PBCA-NP), whichour research group have studied for several years, is a new passive targetingpreparation for liver cancer. Up to now no literature is available on the clinical use ofMMC-PBCA-NP yet. In this investigation, antineoplastic antibiotic MMC, as themodel drug, was enwrapped by a macromoleculer drug carrier BCA, formingnanoparticles about 100nm. The purpose of this research is to study thebiocompatibility and stability of MMC-PBCA-NP freeze-dried powder based on theoptimization of the MMC-PBCA-NP preparation process. Purification, sterilizationmethod and freeze-drying craft of MMC-PBCA-NP formulation were also discussed.First, MMC-PBCA-NP coarse emulsion was prepared by emulsionpolymerization method in bunsen beaker. The treatment for about 3 hours in ice bathand lucifuge under stirring resulted in the formation of a coarsely dispersed colloidalsolution. And then the coarse emulsion was processed through microfluidizer, whichis known as a high-pressure homogenizer, until a more homogeneous and stablecolloid solution was obtained. The working principle of the high-pressurehomogenizer consists in multiply repeated passage of the product through a microslit in the valve. The forces of turbulent flow pulsations, developed by the pressuregradient, produce comminucation and homogenization of the material, rendering ithomogeneous with respect to the particle size distribution in the dispersed phase. Thesurface of the nanoparticle was circular and smooth observed in transmission electronmicroscopy (TEM). The particle size and distribution of MMC-PBCA-NP wasdetermined by photo correlation spectroscopy (PCS). The encapsulation efficiency(EE) and drug loading(DL) were examined by ultraviolet spectrophotometer (UV).The results showed that the mean number diameter (Dn), the EE and DL ofMMC-PBCA-NP were 102±5.85nm, 85.27±1.50％, 6.97±0.14％, respectively. Itwas shown that the purification of MMC-PBCA-NP was freezing centrifuged at 4℃,20000 rpm for 30 min and washed for three times, while the sterilization method wasthat sterilized the MMC-PBCA-NP colloid solution by 60Co radiation for 7.5h at thedosage of 6kGy, the freeze-dry protector was lactase of 5％.The second part of this thesis concentrated on the study of the biocompatibilityof MMC-PBCA-NE By single iv KM mice MMC, MMC-PBCA-NP and PBCA-NPfour different dosages and observed the toxicity reaction for 14 days, the results ofthe acute toxicity testing showed that the LD50 values of MMC,MMC-PBCA-NPand PBCA-NP were 12.2 mg.kg-1, 52.8 mg.kg-1and296.3 mg.kg-1 separately, whichindicated that the MMC-PBCA-NP was less toxic than MMC, and PBCA-NP had thelowest toxicity activity. The hemolytic testing showed that the MMC-PBCA-NPsolution had no hemolytic activities and pyrogen testing displayed that theMMC-PBCA-NP solution had no pyrogen, which initially evinces that thispreparation can be used as intravenous injection.In the last part of this thesis, the stability of MMC-PBCA-NP freeze-driedpowder was investigated by acceleration testing in the temperature of 40±2℃and thehumidity of 75±5％for 3 months. Sampling was conducted every month to check the Dn, DL, PH and redispersion etc. For comparison, the ambient temperaturestability of MMC-PBCA-NP colloidal solution was also studied at the roomtemperature for three months and checked for the Dn, DL, PH and so on. The resultsof the acceleration testing manifested that the Dn,DL,and PH had no evidentvariation, while the results of the room temperature stability testing showed the Dnbecame bigger while the DL smaller as time went by, which means that lyophilizingMMC-PBCA-NP colloidal solution into freeze-dry powder can markedly increasethe stability of MMC-PBCA-NRBased on the results mentioned above, it can be concluded that theMMC-PBCA-NP prepared by emulsion polymerization method and microfluidizertechnology had good biocompatibility and stability after gelsiccation, and therefore, isa promising drug formulation which needs a further and enlarge research.
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