紫杉醇纳米脂质体凝胶剂的制备及体外透皮研究

Preparation and in Vitro Transdermal Diffusion Characteristics of Paclitaxel Nano-liposomes Gels

关键词:  紫杉醇  纳米脂质体凝胶剂  正交试验  经皮渗透

Key words:  paclitaxel  nano-liposomes gels  orthogonal design  transdermal penetration

摘要:

目的 制备紫杉醇纳米脂质体凝胶剂，考察其粒径、粒径分布、包封率、体外释放度及透皮特性。方法 采用薄膜蒸发高压微射流法制备紫杉醇纳米脂质体，以卡波姆为凝胶基质，研制紫杉醇纳米脂质体凝胶剂，采用正交试验探索最佳工艺。用粒径测定仪测定脂质体的粒径及其粒径分布，低速-超速相结合法测定包封率，透析膜扩散法进行体外释放试验，以离体小鼠皮结合改良Franz扩散装置考察其体外透皮特性。结果 紫杉醇纳米脂质体的最佳工艺：卵磷脂的含量为2%，药物与磷脂质量比为1∶30，磷脂与胆固醇的质量比为10∶1。测得的粒径为81.8 nm；粒径分布系数为0.180；平均包封率73.2%。纳米脂质体凝胶剂72 h累积释放百分率为79.04%；48 h的单位面积累积渗透量为429.68 μg·cm^-2。结论 该制剂制备工艺简单，易于涂布，具有较高的包封率，粒径较小且分布均匀，体外释放缓慢。纳米脂质体能促进脂溶性药物紫杉醇透过皮肤。

Abstract:

OBJECTIVE To prepare the paclitaxel nano-liposomes gels, detect the particle size, particle diameter, the entrapment efficiency, the release and transdermal diffusion characteristics in vitro. METHODS Paclitaxel nano-liposomes were prepared using thin film evaporation high pressure microfluidization, added carbomer to prepare the paclitaxel nano-liposomes gels, and the optimal method was determined by the orthogonal test. The particle size, particle diameter of the modified liposomes was detected by nanoparticle size analyzer. The entrapment efficiency was determined by low-speed combination method with HPLC. The release study adopting membrane diffusion method. Using Franz diffusion cell and rats skin to investigate transdermal diffusion characteristics of the modified nano-liposomes gels in vitro. RESULTS The optimal formulation and preparing conditions were as the following: the content of lecithin was 2%, drug∶lecithin=1∶30, lecithin∶cholesterin=10∶1. The particle size of the liposome prepared was 81.8 nm. The particle size distribution coefficient was 0.180. The average entrapment efficiency of the liposomes was up to 73.2%. The release amount of nano-liposomes gels was 79.04% at 72 h and the cumulative penetration amount per unit area was 429.68 μg·cm^-2 at 48 h. CONCLUSION This preparation is prepared with simple technology and the entrapment efficiency of the paclitaxel is high. The particle sizes are small and uniform. Nano-liposomes gels feature a sustained release in vitro, the nano-liposomes can increase diffusion rate of paclitaxel through the skin of rats.