Engineering of Layered Nanocarriers of Quercetin for the Treatment of Diabetes Using Box‐Behnken Design

Abstract Layered nanocarriers are polymeric systems integrated with layers of glucose‐responsive polymers and polyethylene glycol monomethyl ether 2000 PEG 2000 to enhance the targeting effect and release kinetics. The prime purpose of this research study is to demonstrate a controlled release of Quercetin from formulation of quercetin (Qu)‐based layered nanocarriers (LNCs) with higher stability and anti‐diabetic activity. The QuLNCs are synthesized using the nanoprecipitation method and optimized by Box‐Behnken design of the Design of Experiment (DoE) method. The Quercetin Nanoparticles (QuNPs) are prepared using Polyvinyl alcohol (PVA) and Poly (D,L‐ lactic‐co‐glycolic acid) (PLGA) polymers where the two layers of Phenylboronic acid (PBA) are conjugated using 3‐amino propyl‐triethoxysilane (APTES) as a functionalizing agent followed by PEGylation of the entire system using PEG 2000 . The optimized QuLNCs are characterized by various parameters like Particle size (PS), Zeta potential (ZP), % Entrapment efficiency (%EE), Attenuated total reflectance‐ Fourier Transform Infrared Spectroscopy (ATR‐FTIR), Differential scanning Calorimetry (DSC), Transmission electron microscopy (TEM), in vitro as well as in vivo studies. The QuLNCs showed a % entrapment efficiency of 82.846 ± 0.957% and release of 85.04 ± 3.21% of Qu for 24 h from the layered nanocarriers. The in vivo studies of QuLNCs exhibited a significant controlled release of quercetin for modulating blood glucose levels. Hence, these results proved QuLNCs system acts as a favorable approach for the treatment of type 1 diabetes to offer a longer duration of action.