Rajinikanth Paruvathanahalli Siddalingam, Chellian Jestin
School of Pharmacy, Taylors University; School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
Int J Nanomedicine. 2016 Oct 5;11:5067-5077. doi: 10.2147/IJN.S117511. eCollection 2016.
The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol ATO 5 (glyceryl palmitostearate) and Labrasol were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 μg/cm/h) as compared with plain 5-FU gel (2.85±1.12 μg/cm/h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations.
本研究的目的是开发一种基于纳米结构脂质载体（NLC）的水凝胶，并研究其用于5-氟尿嘧啶（5-FU）局部给药的潜力。分别选择Precirol ATO 5（甘油棕榈硬脂酸酯）和Labrasol作为固体和液体脂质相。选择泊洛沙姆188和Solutol HS15（聚氧乙烯-15-羟基硬脂酸酯）作为表面活性剂。将所开发的脂质制剂分散在1%卡波姆934（聚丙烯酸）凝胶介质中，以保持局部应用的一致性。5-FU-NLC的平均粒径、zeta电位和多分散指数分别为208.32±8.21 nm、-21.82±0.40 mV和0.352±0.060。透射电子显微镜研究显示5-FU-NLC的尺寸小于200 nm，呈球形。体外药物渗透研究表明，其释放模式为先有初始突释，随后为持续释放，与普通5-FU凝胶（2.85±1.12 μg/cm/h）相比，5-FU-NLC凝胶（10.27±1.82 μg/cm/h）的5-FU渗透速率显著提高。此外，皮肤滞留研究表明，与大鼠皮肤中的5-FU普通凝胶（12.23±3.86 μg/cm）相比，NLC凝胶中的5-FU滞留量显著增加（91.256±4.56 μg/cm）。与5-FU普通凝胶相比，5-FU-NLC凝胶的皮肤刺激性也显著降低。这些结果表明，所制备的载5-FU的NLC具有很大潜力来提高5-FU透过角质层的渗透率，具有大量滞留且皮肤刺激性最小，这是局部应用制剂的前提条件。
