Hsiue Ging-Ho, Wang Chun-Hung, Lo Chun-Liang, Wang Chau-Hui, Li Ju-Pi, Yang Jia-Ling
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 300 Taiwan, ROC.
Int J Pharm. 2006 Jul 6;317(1):69-75. doi: 10.1016/j.ijpharm.2006.03.002. Epub 2006 Apr 17.
Anticancer drug doxorubicin (DOX) was physically loaded into the micelles prepared from poly(2-ethyl-2-oxazoline)-b-poly(L-lactide) diblock copolymers (PEOz-PLLA). PEOz-PLLA consists of hydrophilic segment PEOz and hydrophobic segment PLLA showed pH-sensitivity in the aqueous solution. The DOX-loaded micelle exhibited a narrow size distribution with a mean diameter around 170 nm. The micellar structure can preserve hydrophobic drug DOX under the physiological condition (pH 7.4) and selectively release DOX by sensing the intracellular pH change in late endosomes and secondary lysosomes (pH 4-5). At 37 degrees C, the cumulated released rate of DOX from micelles was about 65% at pH 5.0 in the initial 24 h. Additionally, polymeric micelles had low cytotoxicity in human normal fibroblast HFW cells for 72 h by using MTT assay. Moreover, DOX-loaded micelles could slowly and efficiency decrease cell viability of non-small-cell lung carcinoma CL3 cells. Taken together, PEOz-b-PLLA diblock polymeric micelles may act as useful drug carriers for cancer therapy.
抗癌药物阿霉素(DOX)被物理负载到由聚(2-乙基-2-恶唑啉)-b-聚(L-丙交酯)二嵌段共聚物(PEOz-PLLA)制备的胶束中。PEOz-PLLA由亲水性链段PEOz和疏水性链段PLLA组成,在水溶液中表现出pH敏感性。负载DOX的胶束呈现出窄的尺寸分布,平均直径约为170nm。胶束结构可以在生理条件(pH 7.4)下保留疏水性药物DOX,并通过感知晚期内体和次级溶酶体中的细胞内pH变化(pH 4-5)选择性地释放DOX。在37℃下,在最初的24小时内,DOX从胶束中的累积释放率在pH 5.0时约为65%。此外,通过MTT测定法,聚合物胶束在人正常成纤维细胞HFW细胞中72小时具有低细胞毒性。此外,负载DOX的胶束可以缓慢且有效地降低非小细胞肺癌CL3细胞的细胞活力。综上所述,PEOz-b-PLLA二嵌段聚合物胶束可能作为癌症治疗的有用药物载体。