Food and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
Eur J Pharm Sci. 2018 Feb 15;113:159-170. doi: 10.1016/j.ejps.2017.10.024. Epub 2017 Oct 21.
Coenzyme Q (CoQ) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ nanosuspensions designed to be administered to the lungs by nebulization. Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ formulations. Preparations were identified as nanosuspensions (particle size in the range 35-60nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02μm). Stability tests showed that the most stable formulation, after 90days, was the one containing vitamin-E TPGS, followed by the CoQ-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ.
辅酶 Q（CoQ）是一种抗氧化物质，作为膳食补充剂被推荐用于治疗心血管疾病和癌症，因为它具有保护和免疫刺激作用。本工作的目的是通过高压匀质法制备、表征和研究三种不同的 CoQ 纳米混悬剂，并将其设计用于通过雾化给药到肺部。选择了三种表面活性剂，即卵磷脂、PEG32 硬脂酸酯和维生素 E TPGS，以稳定 CoQ 制剂。制剂被鉴定为纳米混悬剂（粒径范围为 35-60nm）：用维生素 E TPGS 获得的最小颗粒，表现出核壳结构。从商用空气射流雾化器输送的 CoQ 约为加载剂量的 30%。含有 PEG32 硬脂酸酯的纳米混悬剂具有最高的可吸入分数（70.6%）和最小的 MMAD（3.02μm）。稳定性测试表明，经过 90 天，最稳定的制剂是含有维生素 E TPGS 的制剂，其次是 CoQ-卵磷脂制剂。有趣的是，这些制剂也被证明适用于使用其他气溶胶生成机制（如超声和振动网雾化器）的雾化器。研究集中在制剂及其单一成分对 A549 人肺细胞的体外细胞毒性上，结果表明，含有卵磷脂和 PEG 32 硬脂酸酯的制剂没有明显的细胞毒性。单独的维生素 E TPGS 被证明能够破坏质膜，然而，当维生素 E TPGS 存在于含有 CoQ 的制剂中时，细胞损伤会减少。
