Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar (Mohali), Punjab 160062, India.
Biomaterials. 2011 Oct;32(28):6860-74. doi: 10.1016/j.biomaterials.2011.05.079. Epub 2011 Jun 24.
The present investigation consists in the development and characterization of CoQ10 loaded PLGA nanoparticles (CoQ10-NPs, size < 100 nm) by a scalable emulsion-diffusion-evaporation method. Thermal and crystallinity analysis collectively corroborated that CoQ10 was entrapped into the NPs in amorphous form. The lyophilized CoQ10-NPs were found to be stable for a period of 6 months (at room temperature). In vitro cell culture studies indicated that CoQ10-NPs significantly quenched ROS with nearly 10 fold higher efficacy than free CoQ10. Further, positively charged CoQ10-NPs were localized in two major sources of ROS generation: mitochondria and lysosomes. CoQ10-NPs showed improved oral bioavailability (4.28 times) as compared to free CoQ10. Finally remarkably higher hepatoprotective and anti-inflammatory activity of CoQ10-NPs as compared to free CoQ10 was observed due to mitigation of deleterious effects associated with the generation of free radicals. As elucidated by live noninvasive animal imaging, the higher anti-inflammatory activity of CoQ10-NPs can be attributed to significant accumulation of these NPs in the inflamed tissues.
本研究通过可扩展的乳液扩散蒸发法开发并表征了负载 CoQ10 的 PLGA 纳米颗粒（CoQ10-NPs，粒径 <100nm）。热分析和结晶度分析共同证实 CoQ10 以无定形形式包埋在 NPs 中。冻干的 CoQ10-NPs 在室温下稳定保存长达 6 个月。体外细胞培养研究表明，CoQ10-NPs 能显著清除 ROS，其清除效率比游离 CoQ10 高近 10 倍。此外，带正电荷的 CoQ10-NPs 定位于两种主要的 ROS 产生源：线粒体和溶酶体。与游离 CoQ10 相比，CoQ10-NPs 的口服生物利用度提高了 4.28 倍。由于 CoQ10-NPs 减轻了与自由基生成相关的有害影响，因此 CoQ10-NPs 具有更高的肝保护和抗炎活性，明显优于游离 CoQ10。通过活体非侵入性动物成像阐明，CoQ10-NPs 的更高抗炎活性可归因于这些 NPs 在炎症组织中的显著积累。
