The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 3(2) factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and -12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX.
Objectives:This study was aimed to investigate the therapeutic potential of coenzyme Q10 and its combination with metformin on streptozotocin (STZ)-nicotinamide-induced diabetic nephropathy (DN).Materials and Methods:Type 2 diabetes in rats was induced with STZ-nicotinamide. The diabetic rats were treated with coenzyme Q10 (10 mg/kg, p.o.) alone or coenzyme Q10 + metformin. Various parameters of renal function tests such as serum creatinine, urea, uric acid, and markers of oxidative stress such as renal malondialdehyde (MDA) level, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) activity, transforming growth factor-β (TGF-β), and nitrite content were estimated in renal tissues. All treated animal were subjected to histopathological changes of kidney.Result:Diabetic rats showed a significant reduction in renal function, which was reflected with an increase in serum urea, serum creatinine, uric acid. In addition, STZ-nicotinamide caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity and glutathione (GSH) level. Moreover, TNF-α, MPO activity, TGF-β, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-α, MPO activity, TGF-β and nitrite content along with histopathological changes.Conclusions:This finding suggests that the treatment with coenzyme Q10 or metformin showed significant renoprotective effect against STZ-nicotinamide-induced DN. However, concomitant administration of both showed a better renoprotective effect than coenzyme Q10 or metformin alone treatment.
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