Singh Hardevinder Pal, Tiwary Ashok Kumar, Jain Subheet
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, India.
Yakugaku Zasshi. 2010 Mar;130(3):397-407. doi: 10.1248/yakushi.130.397.
In the present study, an attempt was made to develop a cyclodextrin-colchicine complex and to study its effect on skin permeation and deposition of colchicine. Colchicine beta cyclodextrin (BCD) complex was prepared by freeze-drying method and complex formation was confirmed by NMR and in vitro drug release study. Formulation containing cyclodextrin-drug complex showed 6-fold increase in transdermal flux in comparison with drug solution. Skin retention studies were carried out with the objective of determining the depot effect of elastic liposomes in skin. The amount of drug deposited was 12.4-fold higher in case of elastic liposomes of colchicine-cyclodextrin complex (567+/-1.5 microg) than drug solution (46+/-1.1 microg). The biological evaluation of various vesicular formulations and drug solution was carried out using monosodium urate-induced air pouch model. The results of anti-gout activity in rats showed better and sustained biological effects over 24 h measured in terms of exudate volume, reduction in leukocyte count, decrease in inflammatory cell accumulation, and collagen deposition with colchicine-BCD elastic liposomal formulation than drug solution. Hence the present study reveals that colchicine-cyclodextrin-elastic liposomes approach possesses good potential to enhance skin accumulation, prolong drug release, and improve the site-specificity of colchicine.
在本研究中,尝试开发一种环糊精 - 秋水仙碱复合物,并研究其对秋水仙碱皮肤渗透和沉积的影响。通过冷冻干燥法制备秋水仙碱β-环糊精(BCD)复合物,并通过核磁共振(NMR)和体外药物释放研究确认复合物的形成。含环糊精 - 药物复合物的制剂与药物溶液相比,经皮通量增加了6倍。进行皮肤滞留研究以确定弹性脂质体在皮肤中的储库效应。秋水仙碱 - 环糊精复合物弹性脂质体(567±1.5微克)中沉积的药物量比药物溶液(46±1.1微克)高12.4倍。使用尿酸钠诱导的气袋模型对各种囊泡制剂和药物溶液进行生物学评价。以渗出液体积、白细胞计数减少、炎症细胞积累减少和秋水仙碱 - BCD弹性脂质体制剂的胶原蛋白沉积来衡量,大鼠抗痛风活性结果显示,在24小时内比药物溶液具有更好且持续的生物学效应。因此,本研究表明秋水仙碱 - 环糊精 - 弹性脂质体方法具有增强皮肤蓄积、延长药物释放和改善秋水仙碱位点特异性的良好潜力。