Oral bioavailability, therapeutic efficacy and reactive oxygen species scavenging properties of coenzyme Q10-loaded polymeric nanoparticles

• Published in: Biomaterials Vol. 32; no. 28; pp. 6860 - 6874
• Main Authors: Swarnakar, Nitin K, Jain, Amit K, Singh, Raman P, Godugu, Chandraiah, Das, Manasmita, Jain, Sanyog
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2011
• Subjects: Advanced Basic Science; Animals; Anti-inflammatory activity; Bioavailability; Biological Availability; Cell Line; CoQ10; Dentistry; Effectiveness; Female; Free radicals; Freeze Drying; Hepatoprotective activity; Humans; Imaging; In vitro testing; Inflammation - drug therapy; Materials Testing; Mice; Mitochondria; Mitochondria and lysosomes localization; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Nanoparticles - ultrastructure; Oxidative stress; Particle Size; PLGA nanoparticles; Polymers - chemistry; Polymers - pharmacokinetics; Random Allocation; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Surgical implants; Thiobarbituric Acid Reactive Substances - metabolism; Ubiquinone - analogs & derivatives; Ubiquinone - chemistry; Ubiquinone - metabolism; X-Ray Diffraction; Hepatoprotective activity; Oxidative stress; Mitochondria and lysosomes localization; Anti-inflammatory activity; PLGA nanoparticles; CoQ10
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2011.05.079

Abstract 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.