Development of potent oral nanoparticulate formulation of coenzyme Q10 for treatment of hypertension: Can the simple nutritional supplements be used as first line therapeutic agents for prophylaxis/therapy?

Coenzyme Q10 (CoQ10) is an antioxidant with well-established pharmacological activities against several chronic diseases; however, it is marketed only as a nutritional supplement without any claims of its therapeutic activity and one of the reasons for this could be the poor oral bioavailability rendering difficulties in administering this molecule to achieve therapeutic concentrations. Therefore, the present investigation was aimed at improving the oral bioavailability of CoQ10 by delivering it as nanoparticulate formulation. Biodegradable nanoparticulate formulations based on poly(lactide-co-gylcolide) (PLGA) were prepared by emulsion technique using quaternary ammonium salt didodecyldimethylammonium bromide (DMAB) as a stabilizer. The effect of initial CoQ10 loading on entrapment efficiency and the particle size was studied using 5-75% initial load resulting in good entrapment efficiency (61-83%) without any appreciable increase in the particle size for 5-30% loading (107-110 nm). However, 50% and 75% led to increase in particle size with no appreciable changes in entrapment efficiency. The intestinal uptake of CoQ10 as a suspension in carboxymethylcellulose (CIVIC), a commercial formulation and the developed nanoparticulate formulation was studied in male Sprague-Dawley (SD) rats and found to be 45%, 75% and 79%, respectively, suggesting that solubility and permeability related problems of CoQ10 were overcome by nanoparticulate formulation. Furthermore, the developed nanoparticulate formulation was evaluated for its therapeutic potential in renal hypertensive animals (Goldblatt 2K1C model), demonstrating improved efficacy at a 60% lowered dose as compared to CoQ10 suspension and superior efficacy than the commercial formulation at an equal dose. Together, these results indicate the potential of nanotechnology in improving the therapeutic value of molecules like CoQ10, facilitating its usage as first line therapeutic agent thus revolutionizing its role in current medical therapy. (c) 2007 Elsevier B.V. All rights reserved.