Bilensoy Erem, Gürkaynak Oya, Doğan A Lale, Hincal A Atilla
Hacettepe University Faculty of Pharmacy Department of Pharmaceutical Technology, 06100 Ankara, Turkey.
Int J Pharm. 2008 Jan 22;347(1-2):163-70. doi: 10.1016/j.ijpharm.2007.06.051. Epub 2007 Jul 5.
Paclitaxel is a potent anticancer agent with limited bioavailability due to side-effects associated with solubilizer used in its commercial formulation and the tendency of the drug to precipitate in aqueous media. In this study, paclitaxel was encapsulated in amphiphilic cyclodextrin nanoparticles. Safety of blank nanoparticles was compared against commercial vehicle cremophor:ethanol (50:50 v/v) by hemolysis and cytotoxicity experiments. Data revealed that nanoparticles caused significantly less hemolysis. Results were confirmed with SEM imaging of erythrocytes treated with nanospheres, nanocapsules or commercial vehicle. Cytotoxicity of the blank carriers was evaluated against L929 cells. A vast difference between the cytotoxicity of nanoparticles and cremophor:ethanol mixture was observed. Physical stability of paclitaxel in nanoparticles was assessed for 1 month with repeated particle size and zeta potential measurements and AFM imaging. Recrystallization of paclitaxel, very typical in diluted aqueous solutions of the drug, did not take place when the drug is bound to cyclodextrin nanoparticles. Anticancer efficacy of paclitaxel-loaded nanoparticles was evaluated in comparison to paclitaxel in cremophor vehicle against MCF-7 cells. Cyclodextrin nanoparticle caused a slightly higher anticancer effect than cremophor:ethanol vehicle. Thus, amphiphilic cyclodextrin nanoparticles emerged as promising alternative formulations for injectable paclitaxel administration with low toxicity and equivalent efficacy.
紫杉醇是一种强效抗癌药物，但其商业制剂中使用的增溶剂会带来副作用，且该药物在水性介质中易沉淀，导致其生物利用度有限。在本研究中，紫杉醇被包裹于两亲性环糊精纳米颗粒中。通过溶血和细胞毒性实验，将空白纳米颗粒的安全性与商用载体聚氧乙烯蓖麻油：乙醇（50:50 v/v）进行了比较。数据显示，纳米颗粒引起的溶血明显较少。用纳米球、纳米胶囊或商用载体处理红细胞后的扫描电子显微镜成像证实了该结果。评估了空白载体对L929细胞的细胞毒性。观察到纳米颗粒与聚氧乙烯蓖麻油：乙醇混合物的细胞毒性存在巨大差异。通过重复测量粒径、zeta电位以及原子力显微镜成像，对紫杉醇在纳米颗粒中的物理稳定性进行了为期1个月的评估。当药物与环糊精纳米颗粒结合时，在该药物的稀释水溶液中非常典型的紫杉醇重结晶现象并未发生。与载于聚氧乙烯蓖麻油载体中的紫杉醇相比，评估了载紫杉醇纳米颗粒对MCF-7细胞的抗癌疗效。环糊精纳米颗粒产生的抗癌效果略高于聚氧乙烯蓖麻油：乙醇载体。因此，两亲性环糊精纳米颗粒成为用于注射用紫杉醇给药的有前景的替代制剂，具有低毒性和等效疗效。
