Bioactive Luteolin Entrapped Chitosan-PLGA Nanoparticles: Formulation Optimization to In-Vivo Preclinical Evaluation

Diabetes mellitus is an incurable metabolic disease characterized by a change in blood glucose level. Luteolin (LT) is a bioactive flavonoid and reported for potential antidiabetic activity. LT loaded chitosan (CH)-polylactic co-glycolic acid (PLGA) nanoparticles (NPs) were prepared by emulsification-evaporation process and further optimized by Box-Behnken design using CH (A), PLGA (B), and polyvinyl alcohol (C) as formulation variables and their effect evaluated on particle size (Y-1), drug loading (Y-2), and entrapment efficiency (Y-3). CH-PLGA-LT-NPs showed a particle size of 273.43 +/- 5.24 nm, DL of 15.25 +/- 2.43%, and EE of 65.28 +/- 1.76%. The zeta potential was found to be positive with spherical surface morphology. CH-PLGA-LT-NPs exhibited sustained drug release (68.23 +/- 6.17%) than LT-dispersion (29.66 +/- 4.2%). The permeation study and pharmacokinetic study results revealed 3.19 fold as well as 2.63 fold (AUC(0-t)) enhancement in pure LT. CH-PLGA-LT-NPs also exhibited a significant (P < 0.05) reduction in blood glucose level in streptozotocin-induced diabetic rats than LT-dispersion. CH-PLGA-LT-NPs also showed notable improvement in biochemical parameters as compared to diabetic control and LT-dispersion group. The results concluded that LT-CH-PLGA-NPs is a good alternative to the treatment of diabetes.