Baek Jong-Suep, Pham Cuong Viet, Myung Chang-Seon, Cho Cheong-Weon
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, South Korea.
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, South Korea.
Int J Pharm. 2015 Nov 30;495(2):701-9. doi: 10.1016/j.ijpharm.2015.09.054. Epub 2015 Sep 28.
Tadalafil is a phosphodiesterase-5 inhibitor indicated for the treatment of erectile dysfunction. In this study, we prepared and evaluated transdermal nanostructured lipid carriers (NLC) to improve the skin permeability of tadalafil. Tadalafil-loaded NLC dispersions were prepared using glyceryl monostearate as a solid lipid, oleic acid as a liquid lipid, and Tween 80 as a surfactant. We characterized the dispersions according to particle size, polydispersity index, zeta potential, encapsulation efficiency, and transmission electron microscopy. In vitro skin permeation studies were carried out using Franz diffusion cells, and cytotoxicity was examined using HaCaT keratinocyte cell lines. Tadalafil skin permeability increased for all tadalafil-loaded NLC formulations. The tadalafil-loaded NLC dispersion with ethanol and limonene as skin permeation enhancers exhibited the highest flux (∼4.8-fold) compared to that observed with tadalafil solution alone. Furthermore, a tadalafil-loaded NLC gel with selected permeation enhancers showed tolerance against toxicity in HaCaT cells. These results suggest that the NLC formulations with ethanol and limonene as skin permeation enhancers could be a promising dermal delivery carrier for tadalafil.
他达拉非是一种磷酸二酯酶-5抑制剂，用于治疗勃起功能障碍。在本研究中，我们制备并评估了透皮纳米结构脂质载体（NLC）以提高他达拉非的皮肤渗透性。以单硬脂酸甘油酯为固体脂质、油酸为液体脂质、吐温80为表面活性剂制备了载他达拉非的NLC分散体。我们根据粒径、多分散指数、zeta电位、包封率和透射电子显微镜对分散体进行了表征。使用Franz扩散池进行体外皮肤渗透研究，并使用HaCaT角质形成细胞系检测细胞毒性。所有载他达拉非的NLC制剂的他达拉非皮肤渗透性均有所提高。与单独使用他达拉非溶液相比，以乙醇和柠檬烯作为皮肤渗透促进剂的载他达拉非NLC分散体表现出最高的通量（约4.8倍）。此外，含有选定渗透促进剂的载他达拉非NLC凝胶对HaCaT细胞具有毒性耐受性。这些结果表明，以乙醇和柠檬烯作为皮肤渗透促进剂的NLC制剂可能是一种有前景的他达拉非皮肤给药载体。
