School of Pharmaceutical Sciences of Ribeirão Preto, Department of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Mater Sci Eng C Mater Biol Appl. 2020 May;110:110639. doi: 10.1016/j.msec.2020.110639. Epub 2020 Jan 7.
In this study, we developed a water-in-oil microemulsion containing vitamin A (retinol) and vitamin E (α-tocopherol), which serves as a multifunctional nanosystem that co-delivers antioxidants and displayed additive effect against acute skin inflammation. Microemulsion (ME) was prepared by mixing a surfactant blend (Tween 80 and propylene glycol, 5:1) with isopropyl myristate and water (ratio of 50:40:10, respectively). Vitamin A (0.05% w/w concentration) and/or vitamin E (0.1% w/w concentration) were incorporated into the surfactant mixture of ME by stirring with a magnetic stirrer for 30 min. This multifunctional ME displayed physical stability, with low cytotoxicity in 3T3 cell line, as well as cellular internalization into the cytosol. In vivo treatments using ME delivering α-tocopherol reduced dermal expression of TNF-α by 1.3-fold (p < 0.01), when compared to unloaded ME treatment group. When retinol was added into the ME containing α-tocopherol, it further reduced TNF-α expression by 2-fold (p < 0.001), suggesting the additive effect of vitamin E and vitamin A in the treatment against skin inflammation. In conclusion, we successfully developed the use of water-in-oil ME to pack both vitamin E and vitamin A, and demonstrated for the first time its anti-inflammatory potential when applied topically to TPA-induced inflamed skin.
在这项研究中，我们开发了一种含有维生素 A（视黄醇）和维生素 E（α-生育酚）的油包水乳剂，它作为一种多功能纳米系统，同时递送抗氧化剂，并对急性皮肤炎症表现出相加作用。乳剂（ME）通过将表面活性剂混合物（吐温 80 和丙二醇，5:1）与肉豆蔻酸异丙酯和水（分别为 50:40:10 的比例）混合来制备。通过用磁力搅拌器搅拌 30 分钟，将维生素 A（0.05%w/w 浓度）和/或维生素 E（0.1%w/w 浓度）掺入 ME 的表面活性剂混合物中。这种多功能 ME 表现出物理稳定性，在 3T3 细胞系中具有低细胞毒性，并且能够进入细胞质内。与未负载 ME 处理组相比，用递送 α-生育酚的 ME 进行体内处理可使 TNF-α 的皮肤表达降低 1.3 倍（p<0.01）。当视黄醇被添加到含有 α-生育酚的 ME 中时，它进一步使 TNF-α 的表达降低 2 倍（p<0.001），表明维生素 E 和维生素 A 在治疗皮肤炎症方面具有相加作用。总之，我们成功地开发了使用油包水乳剂来包装维生素 E 和维生素 A，并首次证明了其在局部应用于 TPA 诱导的炎症皮肤时的抗炎潜力。
