Laboratory of Drug Delivery Technology, Department of Drug Sciences, University of Catania, Catania, Italy; Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), Coimbra, Portugal.
Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, P-5001-801 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes e Alto Douro (UTAD), Vila Real, Portugal.
Int J Pharm. 2018 Sep 5;548(1):217-226. doi: 10.1016/j.ijpharm.2018.06.064. Epub 2018 Jun 30.
Essential oils are recognized as valuable active pharmaceutical ingredients attributed to a set of biological properties, which include antibacterial, antifungal, antiviral, antioxidant, anticancer, immune-modulatory, analgesic and anti-inflammatory activities. Their use in pharmaceutics is however compromised by their limited water solubility and low physicochemical stability (i.e. volatility, oxidation). In order to overcome these limitations, we aimed to develop nanostructured lipid carriers (NLC) as delivery systems for Mediterranean essential oils, in particular Rosmarinus officinalis L., Lavandula x intermedia "Sumian", Origanum vulgare subsp. hirtum and Thymus capitatus essential oils, selected on the basis of their antioxidant and anti-inflammatory activities. NLC composed of Softisan (as solid lipid) have been produced by phase inversion temperature (PIT) and high-pressure homogenization (HPH), using two different emulsifiers systems. Particles have been further characterized for their mean particle size, polydispersity, zeta potential, morphology and chemical interactions. Best NLC formulations were obtained with Kolliphor/Labrafil as surfactants, and using Rosmarinus, Lavandula and Origanum as essential oils (PDI between 0.126 and 0.141, Zave < 200 nm). Accelerated stability studies have also been carried out to estimate the effect of the production method and surfactant composition on the long-term stability of EOs-loaded NLC. In vitro biological cell viability and anti-inflammatory activities were evaluated in Raw 264.7 cells (macrophage cell line), while in vitro antioxidant activity was checked by DPPH assay. Lavandula and Rosmarinus NLC were shown to be the most biocompatible formulations up to a concentration of 0.1% (v/v), whereas they were able to induce a dose-dependent anti-inflammatory activity in the order Lavandula > Rosmarinus ≥ Origanum.
精油被认为是具有生物活性的有价值的药物成分，具有一系列生物特性，包括抗菌、抗真菌、抗病毒、抗氧化、抗癌、免疫调节、镇痛和抗炎活性。然而，由于其有限的水溶性和低物理化学稳定性（即挥发性、氧化性），其在药剂学中的应用受到限制。为了克服这些限制，我们旨在开发纳米结构脂质载体（NLC）作为药物传递系统，用于地中海精油，特别是迷迭香罗勒、薰衣草杂交种“Sumian”、牛至和百里香精油，选择它们是基于其抗氧化和抗炎活性。由 Softisan（作为固体脂质）组成的 NLC 通过相转变温度（PIT）和高压匀浆（HPH）生产，使用两种不同的乳化剂系统。进一步对颗粒的平均粒径、多分散性、Zeta 电位、形态和化学相互作用进行了表征。使用 Kolliphor/Labrafil 作为表面活性剂，以及使用迷迭香、薰衣草和牛至作为精油时，获得了最佳的 NLC 配方（PDI 介于 0.126 和 0.141 之间，Zave<200nm）。还进行了加速稳定性研究，以估计生产方法和表面活性剂组成对负载精油的 NLC 长期稳定性的影响。在 Raw 264.7 细胞（巨噬细胞系）中评估了体外细胞活力和抗炎活性，并用 DPPH 测定法检查了体外抗氧化活性。薰衣草和迷迭香 NLC 在 0.1%（v/v）的浓度下表现出最高的生物相容性，而它们能够以薰衣草>迷迭香>牛至的顺序诱导剂量依赖性抗炎活性。
