A Micellar Formulation of Quercetin Prevents Cisplatin Nephrotoxicity

The antioxidant flavonoid quercetin has been shown to prevent nephrotoxicity in animal models and in a clinical study and is thus a very promising prophylactic candidate under development. Quercetin solubility is very low, which handicaps clinical application. The aim of this work was to study, in rats, the bioavailability and nephroprotective efficacy of a micellar formulation of Pluronic F127-encapsulated quercetin (P-quercetin), with improved hydrosolubility. Intraperitoneal administration of P-quercetin leads to an increased plasma concentration and bioavailability of quercetin compared to the equimolar administration of natural quercetin. Moreover, P-quercetin retains overall nephroprotective properties, and even slightly improves some renal function parameters, when compared to natural quercetin. Specifically, P-quercetin reduced the increment in plasma creatinine (from 3.4 +/- 0.5 to 1.2 +/- 0.3 mg/dL) and urea (from 490.9 +/- 43.8 to 184.1 +/- 50.1 mg/dL) and the decrease in creatinine clearance (from 0.08 +/- 0.02 to 0.58 +/- 0.19 mL/min) induced by the nephrotoxic chemotherapeutic drug cisplatin, and it ameliorated histological evidence of tubular damage. This new formulation with enhanced kinetic and biopharmaceutical properties will allow for further exploration of quercetin as a candidate nephroprotector at lower dosages and by administration routes oriented towards its clinical use.

Automated summary

This study demonstrated that a micellar formulation of Pluronic F127-encapsulated quercetin (P-quercetin) was more effective in increasing the bioavailability of quercetin and protecting the kidneys in rats when compared to natural quercetin. P-quercetin not only reduced plasma creatinine and urea levels induced by the nephrotoxic drug cisplatin, but also improved some renal function parameters. The new formulation with enhanced properties can potentially lead to the development of quercetin as a nephroprotective agent in clinical settings at lower dosages.