抗癌复方硫酸长春新碱脂质体的体外释药特性及小鼠体内的组织分布

目的研究复方硫酸长春新碱脂质体的制备方法并考察其体外释放规律以及在小鼠体内的组织分布。方法采用pH梯度法合并逆相蒸发制备同时包载硫酸长春新碱(VCR)和盐酸米托蒽醌(MTO)的复方脂质体，实验考察脂质体的体外释药特性；采用反相高效液相法测定小鼠组织中的VCR和MTO浓度。结果体外释放结果表明，复方脂质体中VCR在24 h释放完全，对照溶液中VCR在6 h释放完全，脂质体中MTO在288 h仅释放了0.05%，对照溶液中MTO在12 h释放完全；体内药动学结果表明复方脂质体在血浆中VCR的AUC是对照溶液的1.70倍，T_1/2(Ke)为对照溶液的1.14倍；MTO的AUC是对照溶液的40.62倍，T_1/2(Ke)为对照溶液的432倍。结论 与对照液比较，体外释放实验证实复方脂质体具有缓释特性，体内实验结果表明复方脂质体可延长药物在血液中的循环时间并且提高了药物在血液中浓度，改善了原药的体内分布特性。

Release profile of compound liposomes entrapped with vincristine sulfate and mitoxantrone chlorhydric acid in vitro and their distribution in mice

AIM: To study on the release profile in vitro and biodistribution in mice of the compound liposomes carried with vincristine sulfate (VCR) and mitoxantrone chlorhydric acid (MTO). METHODS: The release behaviors of the VCR and MTO from compound liposomes were studied in vitro. HPLC was developed for the determination of the contents of VCR and MTO in tissues in mice. RESULTS: The release time of VCR from compound liposome was 24 h and that from free drug (in control solution) was 6 h. The release of MTO from compound liposome was 0.05% after 288 h and release time of MTO from free drug (in control solution) was 12 h. The liposomes and free drugs were injected intravenously at same dose to mice. The elimination half-life time (T 1/2) in plasma of liposomal and free VCR were 0.16 h and 0.14 h, and the AUCs (0 - 48 h) of them were 2.69 (ug x g(-1)) x h and 1.58 (ug x g(-1)) x h, respectively. The elimination half-life times (T 1/2) in plasma of liposomal and free MTO were 21.6 h and 0.05 h and the AUCs (0 - 48 h) of them were 17.06 (ug x g(-1)) x h and 0.42 (ug x g(-1)) x h, respectively. CONCLUSION: The compound liposome with high entrapping efficiency and small particle size could be prepared by pH-gradients method and reverse evaporation technique. Two drugs were sustained-released from the compound liposome. Mice tail intravenous injection of compound liposomes showed that compound liposome prolonged the retention time and improved the concentration of MTO and VCR in the blood circulation system compared to control. In the mean time, compound liposome reduced the concentration of the MTO and VCR in heart, lung, kidney etc. These observations indicated that compound liposome could improve anticancer activity and reduce side effect.