Memisoglu-Bilensoy Erem, Doğan A Lale, Hincal A Atilla
Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
J Pharm Pharmacol. 2006 May;58(5):585-9. doi: 10.1211/jpp.58.5.0002.
Nanoparticles were prepared using beta-CDC6, which is an amphiphilic beta-cyclodextrin derivative modified on the secondary face with 6C aliphatic esters. A nanoprecipitation technique was used to prepare the blank nanoparticles without any surfactant and nanoparticles containing Pluronic F68 as surfactant in a concentration range of 0.1 to 1%. Nanoparticle formulations were characterized by particle size distribution and zeta potential measurements. Entrapment efficiency and in-vitro release profiles were determined and the cytotoxicity of these injectable nanospheres was evaluated against mouse fibroblast L929 cell line and human polymorphonuclear cells by methlythiazolyltetrazolium assay. As far as particle size and zeta potential are concerned, there is a relationship between surfactant presence and nanoparticle characteristics. However, these effects are not significant. It was also found that surfactant presence has no effect on model drug nimodipine encapsulation but accelerates the in-vitro release of the drug. Cell culture studies on mouse fibroblasts and human polymorphonuclear cells revealed a concentration-dependent cytotoxicity more pronounced in fibroblast cells. This led to the conclusion that the use of surfactants in injectable nanoparticles prepared from amphiphilic beta-cyclodextrins may lead to altered in-vitro properties and impaired safety for the drug delivery system.
使用β-CDC6制备纳米颗粒，β-CDC6是一种在二级面上用6C脂肪族酯修饰的两亲性β-环糊精衍生物。采用纳米沉淀技术制备不含任何表面活性剂的空白纳米颗粒以及含有浓度范围为0.1%至1%的普朗尼克F68作为表面活性剂的纳米颗粒。通过粒度分布和zeta电位测量对纳米颗粒制剂进行表征。测定包封率和体外释放曲线，并通过甲基噻唑基四氮唑法评估这些可注射纳米球对小鼠成纤维细胞L929细胞系和人多形核细胞的细胞毒性。就粒径和zeta电位而言，表面活性剂的存在与纳米颗粒特性之间存在关系。然而，这些影响并不显著。还发现表面活性剂的存在对模型药物尼莫地平的包封没有影响，但会加速药物的体外释放。对小鼠成纤维细胞和人多形核细胞的细胞培养研究显示，浓度依赖性细胞毒性在成纤维细胞中更为明显。由此得出结论，在由两亲性β-环糊精制备的可注射纳米颗粒中使用表面活性剂可能会导致体外性质改变以及药物递送系统的安全性受损。
