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酒石酸长春瑞滨长循环脂质体的包封率测定及药效研究

Encapsulation efficiency and efficacy of vinorelbine tartrate long-circulating liposomes

  • 摘要: 以超滤法对酒石酸长春瑞滨(VBT)长循环脂质体包封率的测定方法进行研究,并观察VBT脂质体注射液的体内抗肿瘤作用。采用薄膜蒸发-高压乳匀法制备VBT长循环脂质体,以超滤法分离脂质体和游离药物检测其包封率,并建立了小裸鼠实体瘤HT-29抗肿瘤模型,脂质体组给药剂量为3 mg/kg和6 mg/kg,阳性VBT注射液对照组为6 mg/kg,阴性对照组为0.9% NaCl,尾静脉给药。结果发现,超滤法能将脂质体与游离药物很好地分离,游离药物回收率为99.3%~101.1%,加样回收率为97.2%~98.7%。VBT长循环脂质体以6和3 mg/kg给药后,对实体瘤HT-29的抑瘤率分别为84.9%和54.4%,阳性VBT注射液对照组抑瘤率为27.6%,二者有显著性差异(P<0.01)。采用超滤-HPLC法能有效测定VBT长循环脂质体的含量及包封率;高剂量及低剂量组VBT长循环脂质体的体内抗肿瘤作用均显著优于高剂量VBT注射液。

     

    Abstract: The aim of this study was to determine the encapsulation efficiency of vinorelbine tartrate (VBT) liposomes by the ultrafiltration method and to assess the efficacy of VBT liposome on colon carcinoma in the nude mice.VBT long-circulating liposome were prepared by film dispersion-homogenization method,and free drug from the liposomes was separated by ultrafiltration method.The colon carcinoma models of BALB/C nude mice were created using HT-29 cells,and were divided into four groups for the administration of VBT liposomes at 3 mg/kg,VBT liposomes at 6 mg/kg, VBT solution at 6 mg/kg, and 0.9% NaCl. The results showed that the separation of free drug from VBT liposomes resulted in free drug recovery of 99.3%-101.1% and the added recovery of 97.2%-98.7%.The tumor inhibition ratios for 6 mg/kg and 3 mg/kg were 84.9 % and 54.4 %,both of which were significantly higher than that of free VBT group (27.6 %).The present work not only proposed the method of liposomes that is proved to be good encapsulation efficiency of VBT, but also improve their efficacy on colon carcinoma if compared to positive control group.

     

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