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载辅酶 Q10 的鱼油基大分子胶束递药系统:经猪皮渗透及与鱼油脂肪酸相互作用的考察。

Coenzyme Q10-Loaded Fish Oil-Based Bigel System: Probing the Delivery Across Porcine Skin and Possible Interaction with Fish Oil Fatty Acids.

机构信息

Center for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia.

Lahore Pharmacy College (A Project of Lahore Medical and Dental College), Tulspura Canal Bank, Lahore, 53400, Pakistan.

出版信息

AAPS PharmSciTech. 2018 Apr;19(3):1116-1123. doi: 10.1208/s12249-017-0923-x. Epub 2017 Nov 27.

Abstract

Coenzyme Q10 (CoQ10) is a vitamin-like oil-soluble molecule that has anti-oxidant and anti-ageing effects. To determine the most optimal CoQ10 delivery vehicle, CoQ10 was solubilised in both water and fish oil, and formulated into hydrogel, oleogel and bigel. Permeability of CoQ10 from each formulation across porcine ear skin was then evaluated. Furthermore, the effects of the omega-3 fatty eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from fish oil on skin permeation were investigated by means of nuclear magnetic resonance (NMR) and computerised molecular modelling docking experiments. The highest drug permeation was achieved with the bigel formulation that proved to be the most effective vehicle in delivering CoQ10 across the skin membrane due to a combination of its adhesive, viscous and lipophilic properties. Furthermore, the interactions between CoQ10 and fatty acids revealed by NMR and molecular modelling experiments likely accounted for skin permeability of CoQ10. NMR data showed dose-dependent changes in proton chemical shifts in EPA and DHA. Molecular modelling revealed complex formation and large binding energies between fatty acids and CoQ10. This study advances the knowledge about bigels as drug delivery vehicles and highlights the use of NMR and molecular docking studies for the prediction of the influence of drug-excipient relationships at the molecular level.

摘要

辅酶 Q10(CoQ10)是一种类似维生素的油溶性分子,具有抗氧化和抗衰老作用。为了确定最佳的 CoQ10 传递载体,将 CoQ10 溶解在水中和鱼油中,并制成水凝胶、油凝胶和双凝胶。然后评估 CoQ10 从每种制剂穿过猪耳朵皮肤的渗透性。此外,通过核磁共振(NMR)和计算机分子模拟对接实验研究了鱼油中 ω-3 脂肪酸二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)对皮肤渗透的影响。双凝胶制剂的药物渗透性最高,由于其粘合性、粘性和亲脂性的结合,被证明是在皮肤膜中传递 CoQ10 的最有效载体。此外,NMR 和分子建模实验揭示的 CoQ10 与脂肪酸之间的相互作用可能解释了 CoQ10 的皮肤渗透性。NMR 数据显示 EPA 和 DHA 质子化学位移随剂量呈依赖性变化。分子建模揭示了脂肪酸与 CoQ10 之间的复杂形成和大结合能。本研究提高了对双凝胶作为药物传递载体的认识,并强调了使用 NMR 和分子对接研究预测药物-赋形剂关系在分子水平上的影响。

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