College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan, 712-749, South Korea.
AAPS PharmSciTech. 2014 Feb;15(1):44-51. doi: 10.1208/s12249-013-0034-2. Epub 2013 Sep 25.
The aim of this study was to investigate the capability of two surfactants, Cremophor RH 40 (RH) and Cremophor EL (EL), to prepare liquid crystalline nanoparticles (LCN) and to study its influence on the topical delivery of finasteride (FNS). FNS-loaded LCN was formulated with the two surfactants and characterized for size distribution, morphology, entrapment efficiency, in vitro drug release, and skin permeation/retention. Influence of FNS-loaded LCN on the conformational changes on porcine skin was also studied using attenuated total reflectance Fourier-transform infrared spectroscopy. Transmission electron microscopical image confirmed the formation of LCN. The average particle size of formulations was in the range of 165.1-208.6 and 153.7-243.0 nm, respectively. The formulations prepared with higher surfactant concentrations showed faster release and significantly increased skin permeation. Specifically, LCN prepared with RH 2.5% presented higher permeation flux (0.100 ± 0.005 μgcm(-2)h(-1)) compared with lower concentration (0.029 ± 0.007 μgcm(-2)h(-1)). Typical spectral bands of lipid matrix of porcine skin were shifted to higher wavenumber, indicating increased degree of disorder of the lipid acyl chains which might cause fluidity increase of stratum corneum. Taken together, Cremophor surfactants exhibited a promising potential to stabilize the LCN and significantly augmented the skin permeation of FNS.
本研究旨在考察两种表面活性剂(Cremophor RH 40(RH)和 Cremophor EL(EL))制备液晶纳米粒(LCN)的能力,并研究其对非那雄胺(FNS)经皮传递的影响。用两种表面活性剂制备了载 FNS 的 LCN,并对其粒径分布、形态、包封效率、体外药物释放和皮肤渗透/滞留进行了表征。还使用衰减全反射傅里叶变换红外光谱研究了载 FNS 的 LCN 对猪皮构象变化的影响。透射电子显微镜图像证实了 LCN 的形成。制剂的平均粒径分别为 165.1-208.6nm 和 153.7-243.0nm。表面活性剂浓度较高的制剂表现出更快的释放和显著增加的皮肤渗透。具体而言,与低浓度(0.029±0.007μgcm-2h-1)相比,RH 2.5%制备的 LCN 具有更高的渗透通量(0.100±0.005μgcm-2h-1)。猪皮脂质基质的典型光谱带向更高的波数移动,表明脂质酰基链的无序程度增加,这可能导致角质层流动性增加。综上所述,Cremophor 表面活性剂具有稳定 LCN 的潜力,并显著增加 FNS 的皮肤渗透。