Mahmood Syed, Taher Muhammad, Mandal Uttam Kumar
Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM), Pahang Darul Makmur, Malaysia.
Int J Nanomedicine. 2014 Sep 12;9:4331-46. doi: 10.2147/IJN.S65408. eCollection 2014.
Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon(®) 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 μg/cm(2)/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser scanning microscopy proved an enhanced permeation of coumarin-6-loaded transfersomes, to a depth of approximately160 μM, as compared with rigid liposomes. These ex vivo findings proved that a raloxifene hydrochloride-loaded transfersome formulation could be a superior alternative to oral delivery of the drug.
盐酸雷洛昔芬是一种用于治疗绝经后女性浸润性乳腺癌和骨质疏松症的高效药物，但其口服生物利用度较差，仅为2%。本研究的目的是开发、通过统计学方法优化并表征用于透皮给药的载盐酸雷洛昔芬传递体，以克服该药物生物利用度差的问题。采用响应面法实验设计对传递体进行优化，使用Box-Behnken实验设计。选择磷脂（®）90G、脱氧胆酸钠和超声处理时间，各设三个水平，作为自变量，而包封率、囊泡大小和透皮通量被确定为因变量。通过表面形态和形状、粒径和zeta电位对制剂进行表征。使用Hanson扩散池组件，以大鼠皮肤作为屏障介质，测定离体透皮通量。发现优化制剂的传递体具有球形、单层结构，分布均匀且多分散指数低（0.08）。它们的粒径为134±9 nM，包封率为91.00%±4.90%，透皮通量为6.5±1.1 μg/cm²/小时。与载药传统脂质体和乙醇磷酸盐缓冲盐水相比，载盐酸雷洛昔芬传递体在药物渗透到皮肤中的量和沉积量方面表现出显著优势，增强率分别为6.25±1.50和9.25±2.40。差示扫描量热法研究表明，在离体药物扩散研究中，与对照样品相比，皮肤结构发生了更大的变化。此外，共聚焦激光扫描显微镜证明，与刚性脂质体相比，载香豆素-6传递体的渗透增强，深度约为160 μM。这些离体研究结果证明，载盐酸雷洛昔芬传递体制剂可能是该药物口服给药的一种更好的替代方案。
