Drug Design and Discovery Research Group, University of Saskatchewan, Saskatoon, Canada.
Eur J Pharm Biopharm. 2012 Aug;81(3):548-56. doi: 10.1016/j.ejpb.2012.03.016. Epub 2012 Apr 17.
Various analogs of curcumin show high in vitro cytotoxic activity and are potential candidates for treating a deadly skin disease, melanoma. Due to the low solubility of the drugs, a new delivery agent, namely a cationic gemini surfactant-conjugated β-cyclodextrin, was designed to incorporate novel drug candidates of the 1,5-diaryl-3-oxo-1,4-pentadienyl family. Based on physicochemical parameters, such as particle size and zeta potential, a schematic model for the potential interaction of the drug with the delivery agent was developed. The drug formulations were highly efficient in inhibiting the growth of melanoma cells, with IC(50) values significantly lower than melphalan, the drug currently used for the treatment of in-transit melanoma. CDgemini formulations showed excellent cellular selectivity, triggering apoptosis in the A375 cell line while showing no cytotoxicity to healthy human epidermal keratinocytes. The goal is to develop this novel nanoparticle approach into a non-invasive therapy for in-transit melanoma metastasis that lacks adequate treatment to date.
各种姜黄素类似物在体外显示出很高的细胞毒性，是治疗致命皮肤疾病——黑色素瘤的潜在候选药物。由于药物的溶解度低，因此设计了一种新的递送剂，即阳离子双子表面活性剂结合的β-环糊精，以包载新型的 1,5-二芳基-3-氧代-1,4-戊二烯基家族药物候选物。基于物理化学参数，如粒径和zeta 电位，开发了药物与递送剂潜在相互作用的示意模型。药物制剂在抑制黑色素瘤细胞生长方面非常有效，IC50 值明显低于目前用于治疗转移性黑色素瘤的药物美法仑。CDgemini 制剂表现出优异的细胞选择性，在 A375 细胞系中引发细胞凋亡，而对健康的人表皮角质形成细胞没有细胞毒性。目标是将这种新型纳米颗粒方法开发成一种非侵入性治疗转移期黑色素瘤的方法，目前这种疾病缺乏有效的治疗方法。
