Development of nanotechnology-based drug delivery systems with olive vegetable oil for cutaneous application

ABSTRACT Liquid-Crystalline Systems represent active compounds delivery systems that may be able to overcome the physical barrier of the skin, especially represented by the stratum corneum. To obtain these systems, aqueous and oily components are used with surfactants. Of the different association structures in such systems, the liquid-crystalline offer numerous advantages to a topical product. This manuscript presents the development of liquid-crystalline systems consisting, in which the oil component is olive oil, its rheological characterizations, and the location of liquid crystals in its phase map. Cytotoxic effects were evaluated using J-774 mouse macrophages as the cellular model. A phase diagram to mix three components with different proportions was constructed. Two liquid crystalline areas were found with olive oil in different regions in the ternary diagram with two nonionic surfactants, called SLC1 (S1) and SLC2 (S2). These systems showed lamellar liquid crystals that remained stable during the entire analysis time. The systems were also characterized rheologically with pseudoplastic behavior without thixotropy. The texture and bioadhesion assays showed that formulations were similar statistically (p < 0.05), indicating that the increased amount of water in S2 did not interfere with the bioadhesive properties of the systems. In vitro cytotoxic assays showed that formulations did not present cytotoxicity. Olive oil-based systems may be a promising platform for skin delivery of drugs.

摘要 液晶系统（Liquid-Crystalline Systems）是一类活性物质递送系统，可突破以角质层（stratum corneum）为代表的皮肤物理屏障。该类系统通过表面活性剂（surfactants）复配水相与油相组分制备得到。在这类体系的多种缔合结构中，液晶结构对外用制剂具有诸多优势。本研究构建了以橄榄油为油相组分的液晶系统，并对其开展流变学表征，同时明确了该系统在相图中的液晶相分布位置。本研究以J-774小鼠巨噬细胞（J-774 mouse macrophages）为细胞模型，评估了该系统的细胞毒性效应：通过调控三组分的不同配比构建了三元相图，在以两种非离子表面活性剂（nonionic surfactants）SLC1（S1）与SLC2（S2）构筑的三元体系中，共发现两处分布于不同区域的橄榄油基液晶相区。该体系形成的层状液晶在整个分析周期内均保持稳定；流变学表征结果显示，该类系统呈现假塑性流变行为且无触变性（thixotropy）。质地与生物粘附性实验表明，各组配方的检测结果无统计学显著性差异（p < 0.05），说明S2组中含水量的提升并未对体系的生物粘附特性产生干扰。体外（in vitro）细胞毒性实验结果显示，所有受试配方均未表现出细胞毒性。综上，以橄榄油为基础的液晶系统有望成为药物经皮递送的潜力平台。