Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Department of Post-Graduate Studies & Research in Chemistry, Mangalore University, Mangalagangothri (DK), Karnataka, 574199, India.
AAPS PharmSciTech. 2019 Apr 12;20(4):162. doi: 10.1208/s12249-019-1307-1.
All-trans retinoic acid (ATRA) has been regarded as a wonder drug for many dermatological complications; however, its application is limited due to the extreme irritation, and toxicity seen once it has sufficiently concentrated into the bloodstream from the skin. Thus, the present study was aimed to increase the entrapment of ATRA and minimize its transdermal permeation. ATRA incorporated within nanostructured lipid carriers (NLCs) were produced by a green and facile thin lipid-film based microwave-assisted rapid technique (MART). The optimization was carried out using the response surface methodology (RSM)-driven artificial neural network (ANN) coupled with genetic algorithm (GA). The liquid lipid and surfactants were seen to play a very crucial role culminating in the particle size (< 70 nm), zeta potential (< - 32 mV), and entrapment of ATRA (> 98%). ANN-GA-optimized NLCs required a minimal quantity of the surfactants, formed within 2 min and were stable for 1 year at different storage conditions. The optimized NLC-loaded creams showed a skin retention (ex vivo) to an extent of 87.42% with no detectable drug in the receptor fluid (24 h) in comparison to the marketed cream which released 47.32% (12 h) of ATRA. The results were in good correlation with the in vivo skin deposition studies. The NLCs were biocompatible and non-skin irritant based on the primary irritation index. In conclusion, the NLCs were seen to have a very high potential in overcoming the drawbacks of ATRA for dermal delivery and could be produced conveniently by the MART.
全反式维 A 酸（ATRA）被认为是许多皮肤科并发症的神奇药物；然而，由于其从皮肤充分集中到血液中后会出现极度刺激和毒性，因此其应用受到限制。因此，本研究旨在增加 ATRA 的包封率并最小化其经皮渗透。通过绿色简便的基于薄脂质膜的微波辅助快速技术（MART），将 ATRA 掺入纳米结构脂质载体（NLC）中。通过响应面法（RSM）驱动的人工神经网络（ANN）与遗传算法（GA）的结合进行了优化。发现液体脂质和表面活性剂起着至关重要的作用，导致粒径（<70nm）、Zeta 电位（<-32mV）和 ATRA 的包封率（>98%）。ANN-GA 优化的 NLC 需要最少的表面活性剂，在 2 分钟内形成，在不同的储存条件下可稳定 1 年。与市售乳膏相比，优化的 NLC 载药乳膏在 24 小时时显示出 87.42%的皮肤保留（离体），在受体液中没有检测到药物（24 小时），而市售乳膏在 12 小时时释放了 47.32%的 ATRA。结果与体内皮肤沉积研究具有良好的相关性。NLC 具有生物相容性，根据初级刺激性指数，是非皮肤刺激性的。总之，NLC 具有克服 ATRA 用于皮肤给药的缺点的巨大潜力，并且可以通过 MART 方便地生产。
