Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663# North Zhongshan Road, Shanghai 200062, PR China.
Colloids Surf B Biointerfaces. 2010 Feb 1;75(2):543-9. doi: 10.1016/j.colsurfb.2009.09.034. Epub 2009 Sep 26.
This research is aimed to develop a nanomicelle delivery system in order to enhance the solubility and stability of camptothecin (CPT) in aqueous media. In this case, alpha,beta-poly[(N-carboxybutyl)-L-aspartamide] (PBAsp)-CPT was conjugated by the esterification between PBAsp and 20-OH of CPT, and hence used to fabricate nanomicelles with a particle size between the pore size of blood capillary in normal tissue and that in tumor tissue. It was worthy of note that the drug-loaded system of PBAsp-CPT nanomicelle improved the solubility and stability of CPT in aqueous media. However, with an increase of the CPT loading in PBAsp-CPT, the solubility sharply decreased. Meanwhile, the sizes of PBAsp-CPT nanomicelles showed a tendency of increase. Moreover, the drug release of PBAsp-CPT nanomicelles displayed a linear sustaining profile, and hence resulted in the essential decrease of cytotoxicity to L929 cell line. The assembled nanomicelles based on the PBAsp-CPT conjugates showed a great potential as polymer prodrug of tumor therapy, and the controlled nano-scale might achieve the passive tumor targeting.
本研究旨在开发一种纳米胶束递药系统，以提高喜树碱（CPT）在水介质中的溶解度和稳定性。在这种情况下，通过 PBAsp 和 CPT 的 20-OH 之间的酯化反应将α，β-聚[(N-羧基丁基)-L-天冬酰胺]（PBAsp）-CPT 进行偶联，从而用于制备粒径在正常组织和肿瘤组织毛细血管孔径之间的纳米胶束。值得注意的是，载药系统 PBAsp-CPT 纳米胶束提高了 CPT 在水介质中的溶解度和稳定性。然而，随着 PBAsp-CPT 中 CPT 负载的增加，溶解度急剧下降。同时，PBAsp-CPT 纳米胶束的粒径呈现出增加的趋势。此外，PBAsp-CPT 纳米胶束的药物释放呈现出线性持续的特征，从而导致对 L929 细胞系的细胞毒性显著降低。基于 PBAsp-CPT 缀合物的组装纳米胶束显示出作为肿瘤治疗的聚合物前药的巨大潜力，并且纳米级的控制可能实现被动的肿瘤靶向。
