丝裂霉素-聚氰基丙烯酸丁酯纳米粒制备及体外释药特性

Preparation and in vitro drug-release behaviour of mitomycin-polybutylcyanoacrylate nanoparticles

目的制备具有肝靶向特性的丝裂霉素(mitomycinMMC)-聚氰基丙烯酸正丁酯(polybutylcyanoacrylate,PBCA)纳米粒(MMC-PBCA-NP),并优化制备工艺,使其具有一定的缓释药物特征。方法用乳化聚合法合成MMC-PBCA-NP,用U7(76)表安排实验进行均匀设计,优化工艺条件。纳米粒径及其分布用马尔文激光粒度分析仪测试,用透射电镜(TEM)观察纳米粒形态,用紫外分光光度法在波长365nm处测定纳米粒中MMC含量。结果TEM镜下,纳米粒呈圆形,无粘连,粒度分析仪测定平均粒径为79.89nm,跨距(span)为1.60,纳米制剂的载药量与包封率分别为6.58%与79.03%,远高于国外同类研究的报道,稳定性实验表明,于室温避光条件下,样品储存3个月,载药量与粒径无明显变化。体外累积释药实验表明,前12h释药达22.58%,稍有突释效应,随后基本呈线性关系,缓释达96h。结论该纳米制剂具有较好物理性能与体外缓释特性。

OBJECTIVE To prepare the mitomycin-polybutylcyanoacrylate nanoparticles （MMC-PBCA-NP） for liver-targeting with sustained release behavior. METHODS The MMC-PBCA-NP was prepared based on the emulsion polymerization under the optimal conditions of uniform design arranged with U7（7^6） table. The size and size distribution of nanoparticles （NP） were measured using the Malvern laser mastersizer 3000HS and the morphology of NP was observed by transmission electron microscope（TEM）, rrhe MMC contents in the nanoparticles were measured by means of UV spectra at 365 nm. RESULTS The nanoparticles were discrete and uniform spheres with average diameter 79.87 nm and span 1.60. The loading and incorporation efficiency of MMC-PBCA-NP were 6.58% and 79.03%, respectively, which were higherthan those publicated. The stability test of MMC-PBCA-NP showed no change of drug loading and the diameter of nanoparticles after 3 months under room temperature and dark conditions. The drug release time extended to 96 h with a httle burst effect at the first hour in vitro. CONCLUSION The nanoparticles possess good physical performance and sustained release character in vitro.