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Construction and Evaluation in Vitro and in Vivo of Targeting Sustained Release VCR-loaded Microspheres

Author: LuoHao
Tutor: ChangJin
School: Tianjin University
Course: Materials Science
Keywords: Vincristine PLGA Folate Targeting Sustained release Microspheres Adenoid Cystic Carcinoma
CLC: R94
Type: Master's thesis
Year: 2008
Downloads: 279
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Abstract


The modified W/O/W extraction–evaporation technique was chosen to prepare targeting vincristine-loaded microspheres using poly (lactic-co-glycolic) acid (PLGA). PLGA, the mixture ratio of solvent, the emulsification of inner aqueous phase, the emulsification of outer aqueous phase were researched. After orthogonal experiment, the highest drug loading of microspheres was found.The microspheres were characterized for morphology by transmission electronic microscopy (TEM). The particle sizes of microspheres were determined by Particle Size Analyzer. Folate on the surface of microspheres was detected by IR and 1H-NMR. The release performances of VCR-loaded PLGA microspheres in vitro and drug loading were researched. The results showed microspheres were smooth and spherical with a mean particle size 249.2nm, the index of polydispersity was 0.154, and the drug loading was 4.53%. The release of VCR from PLGA microspheres can persist for 14d. After fitting, the release performance was coincided with Higuchi models.In this paper, biocompatibility experiments, inhibition of tumor cells in vitro, and targeting test in cell level were researched. The results showed after empty microspheres and Adenoid Cystic Carcinoma (ACC) cells co-cultured for 5 days, cell viability had remained at more than 80 percent. After inhibitory effect in vitro for 5 days, inhibitory rate was 96%. The inhibition rate was determined by different concentration of VCR and reaction time. Microspheres could find and attach to the ACC cells in 3 hours by targeting effect of FA.The ACC model nude mice were used for researching the therapy effects of VCR- loaded microspheres. The change of tumor volume showed that targeting microspheres group and sustained release microspheres group could significantly enhanced tumor inhibition rate, which were compared with VCR group and control group, tumor inhibition rate was 90 % in 14th day. Histological examination and scanning electronic microscopy (SEM) were used to observe the therapeutic effects in microscopic view. The results showed VCR could be sustained released from targeting microspheres, which could remain sustained therapeutic effect. And targeting microspheres could reduce the side effect of VCR.

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