Zhang Leyang, Sun Minjie, Guo Rui, Jiang Zhiping, Liu Yun, Jiang Xiqun, Yang Changzheng
Laboratory of Mesoscopic Chemistry, Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):2912-20. doi: 10.1166/jnn.2006.431.
This study explored the feasibility of using surface-modified nanoparticulate drug delivery system to enhance the transepithelial transport of antitumor drugs. An antitumor drug, 10-hydroxycamptothecin, was encapsulated into nanoparticles made of biodegradable poly(caprolactone-co-lactide)-PEG-poly(caprolactone-co-lactide) by a novel two-step nano-precipitation method. The obtained nanoparticles had a drug loading content of 10.4% and a size of 256.3 nm, exhibiting a steady and sustained in vitro release profile. By incubation in chitosan containing medium, the drug-loaded nanoparticles could be subsequently surface-modified with chitosan. The surface modification was monitored by dynamic light scattering method, zeta potential observation, and transmission electron microscopy, and its degree could be easily adjusted by varying the concentration of chitosan in the incubation medium. Caco-2 cell monolayer was used as an in vitro model to evaluate the intestinal 10-hydroxycamptothecin absorption. The absorptive transport of 10-hydroxycamptothecin could be improved to some extent by drug loaded nanoparticles and could be further enhanced in the case of surface-modified nanoparticles, suggesting that chitosan surface-modified nanoparticles may be a promising oral delivery system for antitumor drugs.
本研究探讨了使用表面改性的纳米颗粒药物递送系统增强抗肿瘤药物经上皮转运的可行性。通过一种新型的两步纳米沉淀法，将抗肿瘤药物10-羟基喜树碱封装到由可生物降解的聚（己内酯-共-丙交酯）-聚乙二醇-聚（己内酯-共-丙交酯）制成的纳米颗粒中。所制备的纳米颗粒载药量为10.4%，粒径为256.3 nm，在体外呈现出稳定且持续的释放曲线。通过在含壳聚糖的培养基中孵育，载药纳米颗粒随后可被壳聚糖进行表面改性。采用动态光散射法、zeta电位观察和透射电子显微镜对表面改性进行监测，通过改变孵育培养基中壳聚糖的浓度可轻松调节其改性程度。以Caco-2细胞单层作为体外模型评估肠道对10-羟基喜树碱的吸收。载药纳米颗粒可在一定程度上提高10-羟基喜树碱的吸收转运，而表面改性纳米颗粒的吸收转运效果更佳，这表明壳聚糖表面改性纳米颗粒可能是一种有前景的抗肿瘤药物口服递送系统。
