Erdogar Nazlı, Varan Gamze, Bilensoy Erem
Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Sıhhiye-Ankara, Turkey.
Department of Nanotechnology and Nanomedicine, Instıtute of Graduate Studies in Science, Hacettepe University, 06800 Beytepe-Ankara, Turkey.
Curr Top Med Chem. 2017;17(13):1521-1528. doi: 10.2174/1568026616666161222101104.
Villiers has extensively studied cyclodextrins, a family of macrocyclic oligosaccharides linked by α-1,4 glycosidic bonds, in different fields since their discovery in 1891. The unique structure enabling inclusion complexation for natural cyclodextrins and cyclodextrin derivatives make them attractive for novel drug delivery systems. Cyclodextrins can be modified with long aliphatic chains to render an amphiphilic property and these different amphiphilic cyclodextrins are able to form nanoparticles without surfactants. In the literature, several different amphiphilic cyclodextrins are reported and applied to drug delivery and targeting especially to tumors. Specificly, folateconjugated amphiphilic cyclodextrin derivatives are used for active tumor targeting of poorly water soluble drugs and improve the efficacy and safety of therapeutic agents. On the other hand, effect of positive surface charge has also been under research in the recent years. Polycationic amphiphilic cyclodextrins have shown promise towards forming small complexes with negatively charged molecules such as drugs or plasmid DNA. Polycationic amphiphilic cyclodextrins enhance interaction with cell membrane due to their net positive surface charge. The scope of this review is to describe potential uses and pharmaceutical applications of tumor-targeted amphiphilic cyclodextrins, with focus on folate-conjugated cyclodextrin derivatives and polycationic cyclodextrin derivatives both studied by our group at Hacettepe University.
自1891年环糊精被发现以来,维利尔斯在不同领域对其进行了广泛研究。环糊精是一类通过α-1,4糖苷键连接的大环寡糖。天然环糊精及其衍生物独特的结构使其能够形成包合物,这使得它们在新型药物递送系统中颇具吸引力。环糊精可以用长脂肪链进行修饰,以赋予其两亲性,这些不同的两亲性环糊精能够在不使用表面活性剂的情况下形成纳米颗粒。在文献中,报道了几种不同的两亲性环糊精,并将其应用于药物递送和靶向,尤其是肿瘤靶向。具体而言,叶酸偶联的两亲性环糊精衍生物用于难溶性药物的主动肿瘤靶向,并提高治疗剂的疗效和安全性。另一方面,正表面电荷的作用近年来也一直在研究中。聚阳离子两亲性环糊精已显示出与带负电荷的分子(如药物或质粒DNA)形成小复合物的潜力。聚阳离子两亲性环糊精由于其净正表面电荷而增强了与细胞膜的相互作用。本综述的范围是描述肿瘤靶向两亲性环糊精的潜在用途和药物应用,重点是我校研究小组研究的叶酸偶联环糊精衍生物和聚阳离子环糊精衍生物。