长春新碱阳离子纳米结构脂质载体及其小肠吸收的研究

Vincristine Cationic Nanostructured Lipid Carriers and Intestinal Absorption

目的:硫酸长春新碱作为一种细胞毒型抗肿瘤药物,临床上多用其注射剂,虽应用广泛,但存在较多缺点,如药物半衰期短,代谢速率快以及毒副作用明显。本文目的是制备包载长春新碱和十二烷基磺酸钠的阳离子纳米结构脂质载体,并对其进行评价。方法:用复乳挥发法制备出目标脂质纳米粒;利用激光粒度仪对其粒径及zeta电位进行检测;利用高效液相色谱法对其包封率和载药量进行测定;透析法检测纳米粒的体外释放行为;用小肠吸收法评价纳米粒的促进吸收作用。结果:制得的纳米粒的平均粒径为(192.4±4.14)nm,多分散系数(PDI)为0.184±0.015,包封率为32.28%,Zeta电位为(30.6±4.09)m V,载药量为(1.56±0.10)%;体外释放实验显示在pH=7.4的中性释放介质中,硫酸长春新碱脂质纳米粒表现出缓释特性;小肠吸收实验表明十二烷基磺酸钠的加入和阳离子纳米粒的修饰可提高小肠对药物的吸收。结论:阳离子硫酸长春新碱纳米结构脂质载体具有缓释效果,并可以促进小肠对药物的吸收。

Objective： Vincristine sulfate is a kind of cytotoxic anticancer drugs. Although its injection is widely used clinically,there are some drawbacks such as short half-life drugs, rapid metabolic rate and significant side effects should be overcomed. The purpose of this article is to prepare and evaluate the characteristics of nanostructured lipid carriers loaded with vincristine sulfate and sodium dodecyl sulfonate. Methods： The target lipid nanoparticles were prepared by double emulsion volatile; its size and zeta potential were tested by laser particle size analyzer; its encapsulation efficiency and drug loading were measured by HPLC; the release behavior was studied by dialysis method; the promoting effect of nanoparticles＇ absorption was evaluated by intestinal absorption. Results： The average particle size of nanoparticles was（192.4±4.14） nm, the polydispersity index（PDI） was 0.184±0.015, the encapsulation efficiency was32.28 %, Zeta potential was（30.6±4.09） m V, drug loading was（1.56±0.10） %; in vitro release experiments showed that vincristine sulfate lipid nanoparticles exhibit sustained release characteristics when media pH was 7.4; intestinal absorption experiments showed that the addition of sodium dodecyl sulfonate and nanoparticles structure can increase the intestinal absorption of drugs. Conclusions： Vincristine Cationic nanostructured lipid carrier has sustained-release effect, and can promote intestinal absorption of drugs.