Patel Hetal K, Barot Bhavesh S, Parejiya Punit B, Shelat Pragna K, Shukla Arunkumar
Department of Pharmaceutics, K. B. Institute of Pharmaceutical Education and Research, Kadi Sarva Vishwavidyalaya, Sector 23, Gandhinagar, 382023, India.
Department of Pharmaceutics, K. B. Institute of Pharmaceutical Education and Research, Kadi Sarva Vishwavidyalaya, Sector 23, Gandhinagar, 382023, India.
Colloids Surf B Biointerfaces. 2014 Jul 1;119:145-53. doi: 10.1016/j.colsurfb.2014.02.005. Epub 2014 Mar 29.
Vitiligo is a non contagious acquired pigmentation disorder with limited treatment possibilities. Clobetasol propionate (CP) is the drug-of-choice for vitiligo which suppresses the immune system by reducing immunoglobulin action and causes the restoration of melanocytes leading to repigmentation of skin. However, despite being effective, its low and variable bioavailability prompt for development of novel carrier that could effectively target CP to site of action without producing undesirable side-effects. Low solubility of CP in subsequent poor in vivo bioavailability was overcome by formulating microemulsion based gel of CP (MBC) which would enhance the percutaneous transport of CP into and across the skin barrier. Comprehensive characterization of MBC was carried out for viscosity, gel strength and rheological behavior. In vitro studies revealed much higher drug release, skin penetration and enhanced skin accumulation as compared to control (Cream of CP). In vitro and in vivo occlusion studies demonstrated similar occlusiveness for MBC and control. MBC exhibited 3.16 times higher stratum corneum CP levels compared to control. Visualization of cutaneous uptake in vivo using laser scanning microscopy confirmed targeting of CP to epidermis and dermis. Dermatopharmacokinetic studies of MBC showed enhanced drug deposition of CP in skin layers. MBC was assessed for in vivo efficacy by single blind randomized pilot clinical study. The efficacy was assessed by vitiligo area scoring index (VASI) method. After completion of trial, repigmentation of vitiligo patches in patients were evaluated and scored. MBC was superior in terms of faster repigmentation and efficacy when compared with control (p value<0.5). Hence, it was concluded that CP loaded MBC possess enhanced skin localization as well as therapeutic activity in vitiligo patients.
白癜风是一种非传染性的后天性色素沉着紊乱疾病，治疗方法有限。丙酸氯倍他索（CP）是治疗白癜风的首选药物，它通过降低免疫球蛋白的作用来抑制免疫系统，并促使黑素细胞恢复，从而导致皮肤色素沉着恢复。然而，尽管CP有效，但其低且可变的生物利用度促使人们开发新型载体，这种载体可以有效地将CP靶向作用部位，而不会产生不良副作用。通过制备CP的微乳凝胶（MBC）克服了CP低溶解度以及随之而来的体内生物利用度差的问题，该微乳凝胶可增强CP经皮进入并穿过皮肤屏障的转运。对MBC的粘度、凝胶强度和流变行为进行了全面表征。体外研究表明，与对照（CP乳膏）相比，MBC的药物释放、皮肤渗透和皮肤蓄积明显更高。体外和体内封闭研究表明，MBC和对照的封闭性相似。与对照相比，MBC的角质层CP水平高出3.16倍。使用激光扫描显微镜对体内皮肤摄取进行可视化，证实CP靶向表皮和真皮。MBC的皮肤药代动力学研究表明，CP在皮肤层中的药物沉积增加。通过单盲随机试点临床研究评估了MBC的体内疗效。疗效通过白癜风面积评分指数（VASI）方法进行评估。试验完成后，对患者白癜风斑块的色素沉着恢复情况进行评估和评分。与对照相比，MBC在色素沉着恢复速度和疗效方面更优（p值<0.5）。因此，得出结论，负载CP的MBC在白癜风患者中具有增强的皮肤定位以及治疗活性。
