紫杉醇磁性长循环脂质体的研究

Study on long circulating magnetoliposome entrapped paclitaxel

目的 制备紫杉醇磁性长循环脂质体 ,以提高紫杉醇的疗效并降低其不良反应。方法 用逆相蒸发法制备紫杉醇磁性长循环脂质体 ,高效液相色谱法测定药物的含量。大耳白兔药动学考察BALB/C ,小鼠体内分布实验 ,建立了小鼠EMT 6乳腺癌模型 ,静注或腹腔注射给药 ,并计算抑瘤率。结果 紫杉醇磁性长循环脂质体的粒径是 6 4 0nm ,包封率是 96 .6 4 % ,兔体中药动学符合三室模型。体内分布研究表明 :紫杉醇磁性长循环脂质体对小鼠EMT 6肿瘤生长均有较明显的抑制作用 ,抑瘤作用较紫杉醇注射液提高 ;同时 ,可降低药物对心、肺、肾等器官的毒性。结论 紫杉醇磁性长循环脂质体不同给药途径均有一定的肿瘤靶向性和缓释长效作用。

OBJECTIVE: To study the preparation of paclitaxel entrapped long circulating magnetoliposomes (TAX-LMLP) and evaluate its quality. METHODS: TAX-LMLP were prepared by reverse-phase evaporation method. The RP-HPLC method was used for the determination of TAX. The pharmaceutical qualities and tissue distribution were evaluated. EMT-6 breast cancer models were established, the treatment efficacy was evaluated by sc. or ip. TAX preparations. RESULTS: The average diameters of TAX-LMLP were less than 1 μm. The concentration of TAX in the cancer was much higher and that in the heart or kidney was lower than that of TAX injection after administration of TAX-LMLP. The blood concentration-time curves of TAX-LMLP was conformed to a three compartments models. TAX-LMLP showed higher anti-neoplastic activity. CONCLUSION: The results indicated that TAX-LMLP has a good anti-cancer efficiency in vivo and it may decrease the side effects of paclitaxel and improve its treatment effectively.