Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Eur J Pharm Biopharm. 2021 Jun;163:223-239. doi: 10.1016/j.ejpb.2021.04.007. Epub 2021 Apr 14.
In the present study, combinatorial nanostructured lipid carrier gel of 5-fluorouracil and resveratrol was formulated, optimized and characterized to enhance permeation in between epidermis and dermis layers of the skin to obtain a synergistic effect against skin cancer. After extensive trials, a newly modified emulsiosonication method was developed and additionally, for the first time, stability studies were done in the beginning to optimize formulation technique, which exhibited two major benefits simultaneously; first, it provided best-optimized technique for preparation of combinatorial lipid-nanosystem, and secondly, it also demonstrated a detailed report card of durability of formulations. In vitro release study showed a significantly improved, slow and prolonged release of drugs from the optimized lipid-nanosystem (***p < 0.05), which followed non-Fickian Higuchi kinetics. Besides, mechanism of skin permeation enhancement study, dermatokinetic assessment, and depth analysis of optimized formulation on skin exhibited improved permeation and well distribution of drugs up to the dermis layer of skin. Moreover, combinatorial linogel possessed significantly greater efficacy (**p < 0.01) on the A431 cell line, as compared to the conventional formulation. Thus, findings revealed that modified method of preparation for dual drug-loaded lipid-nanosystem lead to the production of a stable formulation that also improved the retention of both 5-fluorouracil and resveratrol in between the epidermis and dermis region of skin thereby helping in the management and treatment of skin cancer.
在本研究中，我们设计、优化并表征了组合式纳米结构脂质载体 5-氟尿嘧啶和白藜芦醇凝胶，以增强药物在皮肤表皮和真皮层之间的渗透，从而获得针对皮肤癌的协同作用。经过广泛的试验，我们开发了一种新的改良乳化超声法，并首次进行了稳定性研究，以优化制剂技术，这同时具有两个主要优势；首先，它为制备组合脂质纳米系统提供了最佳优化技术，其次，它还详细说明了制剂的耐用性报告卡。体外释放研究表明，药物从优化的脂质纳米系统中得到了显著改善、缓慢和持久的释放（***p < 0.05），符合非菲克扩散动力学。此外，皮肤渗透增强机制研究、皮肤药代动力学评估以及对优化配方在皮肤中的深度分析表明，药物的渗透和在皮肤真皮层的分布得到了改善。此外，组合型凝胶在 A431 细胞系中表现出显著更高的疗效（**p < 0.01），优于常规制剂。因此，研究结果表明，改良的双载药脂质纳米系统的制备方法可生产出稳定的制剂，还可提高 5-氟尿嘧啶和白藜芦醇在皮肤表皮和真皮区域的保留，从而有助于皮肤癌的管理和治疗。
