Insulin- and quercetin-loaded liquid crystalline nanoparticles: implications on oral bioavailability, antidiabetic and antioxidant efficacy.

Abstract

The present study reports insulin (INS)- and quercetin (QT)-lyotropic liquid crystalline nanoparticles (LCNPs) with improved bioavailability, antidiabetic and antioxidant efficacy following oral administration. The developed INS-QT-LCNPs were evaluated for simulated gastric fluid stability. In vitro Caco-2 uptake studies were also performed. Furthermore, in vivo pharmacokinetics and pharmacodynamics of INS-QT-LCNPs were evaluated. INS entrapped within LCNPs demonstrated excellent stability in simulated gastric fluid. Higher uptake of fluorescein isothiocyanate-INS-LCNPs were observed in Caco-2 cells. INS-LCNPs demonstrated approximately 20% relative bioavailability compared with subcutaneously administered INS. Significant decrease in oxidative stress was confirmed by reduction in malondialdehyde level. Overall, combination strategy not only overcomes poor oral bioavailability of INS and QT, but also prevents the generation of reactive oxygen species, responsible for diabetes-mediated complications.