Design, synthesis and therapeutic exploration of nano-curcumin targeting the synergistic interactions with p53 and PARP-1 proteins in preventing food-additive induced genotoxicity and diabetic complications

Abstract

The present study brings forth a novel drug delivery system for targeted therapeutic management of diabetes resulting from food-additive consumption, specifically Alloxan (ALX). ALX exert its toxic effects on pancreatic β cells and L6 cells which has been linked to oxidative stress induced DNA damage that predominantly associates key molecular factors like p53 and PARP-1. To address the issue, nutraceutical curcumin (CUR), was repurposed for its prophylactic property against diabetes by encapsulating it in a biodegradable, non-toxic polymer poly-lactide-co-glycolide (PLGA) to form nano-curcumin (NCUR). The in silico molecular docking study also indicated potential binding affinity of CUR with these critical cellular proteins with optimum dock score. NCUR were characterized through AFM, FESEM, DLS, XRD and FTIR studies, which confirmed its average size as 45 nm, negative zeta potential, smooth surface area and purity in nature. The overall experimental findings in mice model and cell line demonstrated that NCUR significantly delayed diabetes onset by mitigating oxidative stress, genotoxicity, and mitochondrial dysfunction by modulating protein expression by virtue of improve drug solubility and effectivity, targeted delivery, bioavailability, and controlled release of CUR from the nano-capsule i.e. NCUR. Thus, this study suggests a therapeutic possibility of NCUR for addressing diabetes and its complications by targeting/ hyper-activating the function of different proteins and modulating other signalling cascades involved therein for providing a better life of diabetics in near future.