Laboratory of Chemical, Galenic and Pharmacological Development of Drugs (LR12ES09), Faculty of Pharmacy of Monastir, University of Monastir, 5000, Monastir, Tunisia.
AAPS PharmSciTech. 2019 Nov 1;20(8):330. doi: 10.1208/s12249-019-1543-4.
The present work attempts to develop and optimize the formula of a lipidic nanoemulsion (NE) containing sodium hyaluronate (HNa) and indomethacin (Ind) as HNa-Ind for enhanced transdermal antiarthritic activity. NEs were prepared by the spontaneous emulsification method and characterized by Fourier-transform infrared (FTIR) spectroscopy. The composition of the optimal formulation was statistically optimized using Box-Behnken experimental design method with three independent factors and was characterized for particle size, polydispersity index, and percent transmittance. The selected formula was tested for its in vitro antioxidant activity and in vivo anti-inflammatory activity. The optimized HNa-Ind NE formula was characterized and displayed a particle size of 12.87 ± 0.032 nm, polydispersity index of 0.606 ± 0.082, and 99.4 ± 0.1 percentage of transmittance. FTIR showed no interaction between HNa and Ind as a physical mixture. In addition, the optimized HNa-Ind NE was able to preserve the antioxidant ability of the two drugs, as evidenced through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition assay used to assess free radical scavenging ability. The cell viability was increased while the free radical scavenging activity was decreased (94.28% inhibition at higher concentrations compared with vitamin C as a reference with an inhibition of 100%). Moreover, the pharmacological anti-inflammatory potential of the optimized HNa-Ind NE formulation was assessed using an in vivo model. Compared with reference drugs (ibuprofen gel 5%), the remarkable activity of the optimized formulation was established using xylene-induced ear edema in mice model, in which the inflamed region reduced by 92.5% upon treatment. The optimized HNa-Ind NE formulation showed considerably higher skin permeation and drug deposition capability compared with the HNa-Ind solution. HNa-Ind NE was demonstrated to be a successful carrier with enhanced antioxidant and anti-inflammatory potential while showing better skin penetration, thus being a promising vehicle for transdermal drug delivery.
本工作试图开发和优化包含透明质酸钠（HNa）和吲哚美辛（Ind）的脂质纳米乳（NE）的配方，以提高其经皮抗关节炎活性。通过自发乳化法制备 NE，并通过傅里叶变换红外（FTIR）光谱进行表征。使用三因素 Box-Behnken 实验设计方法对最佳配方的组成进行统计学优化，并对粒径、多分散指数和透光率进行了表征。选择的配方进行了体外抗氧化活性和体内抗炎活性测试。对优化的 HNa-Ind NE 配方进行了表征，结果显示粒径为 12.87±0.032nm，多分散指数为 0.606±0.082，透光率为 99.4±0.1%。FTIR 显示 HNa 和 Ind 作为物理混合物之间没有相互作用。此外，优化的 HNa-Ind NE 能够保持两种药物的抗氧化能力，这可以通过 2,2-二苯基-1-苦基肼（DPPH）抑制试验来评估自由基清除能力得到证明。细胞活力增加，而自由基清除活性降低（与作为参比的维生素 C 相比，较高浓度下抑制率为 94.28%，抑制率为 100%）。此外，还通过体内模型评估了优化的 HNa-Ind NE 制剂的药理学抗炎潜力。与参比药物（布洛芬凝胶 5%）相比，在小鼠二甲苯诱导的耳肿胀模型中，优化制剂的显著活性得到了证实，治疗后炎症区域减少了 92.5%。与 HNa-Ind 溶液相比，优化的 HNa-Ind NE 制剂显示出更高的皮肤渗透和药物沉积能力。HNa-Ind NE 被证明是一种成功的载体，具有增强的抗氧化和抗炎潜力，同时具有更好的皮肤穿透性，因此是一种有前途的经皮给药载体。
