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Obesity is the major cause of type 2 diabetes with hyperlipidemia as one of its complications and antioxidants were found to be beneficial in such disease conditions. The present investigation is geared towards reduction of the dose required/improve the bioavailability of the combination of antioxidants, ellagic acid and coenzyme Q10 by co-encapsulating them into nanoparticles and study the possible synergism in ameliorating hyperlipidemia in high fat diet fed rats. The co-encapsulated particles at 10% (w/w of polymer) loading of ellagic acid and coenzyme Q10 have particle size of 260 nm. Male Sprague-Dawley (SD) rats on feeding high fat diet for over 4 weeks developed hyperlipidemia. The hyperlipidemic rats on 2 weeks post treatment with antioxidant combination administered as oral suspension or nanoparticles found to ameliorate the hyperlipidemic conditions and nanoparticles were found to be equally/more effective at 3 times lower dose in sustaining cholesterol lowering effect for extended periods, lowering glucose and triglycerides and in improving endothelial functioning, indicating the ability of the nanoparticles in improving efficacy of the duo. The results promise the potential of nanoparticles in improving the efficacy of ellagic acid and coenzyme Q10 in treating high fat diet induced hyperlipidemia in rats.

Atorvastatin calcium (AC) is a second-generation 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor approved for clinical use as a lipid lowering agent. AC, the world's best selling drug is associated with poor oral bioavailability and serious adverse effects like rhabdomyolysis on chronic administration. A biodegradable nanoparticulate approach was introduced here with a view to improving the efficacy and safety of AC. Poly lactide-co-glycolic acid (PLGA) nanoparticles containing atorvastatin calcium were prepared using two stabilizers i.e. didodecyl dimethyl ammonium bromide (DMAB) and Vitamin E tocopheryl polyethylene glycol 1000 succinate (Vit E-TPGS) using a co-solvent approach by emulsion-diffusion-evaporation method. AC loaded PLGA nanoparticles prepared using DMAB and Vit E-TPGS were found to be 120.0 +/- 4.2 nm and 140.0 +/- 1.5 nm (z-average) in size respectively. In vitro release studies at pH 7.4 revealed a zero order release profile for nanoparticles. Efficacy and safety parameters of the prepared nanoparticles against marketed formulation were evaluated in high fat diet fed (hyperlipidemic) rats. It was found that atorvastatin calcium nanoparticles were equally effective in comparison to Lipicure, at a 66%-reduced dose in treating the hyperlipidemia characterized by alterations in PTC, LDL-C, VLDL-C, HDL-C, PTG and PGL in the high fat diet fed rats. On the other hand, when evaluated for safety, nanoparticulate formulation showed no/negligible myotoxicity characterized by lower PC, BUN, CK, LDH and AST levels in comparison to the marketed formulation.

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