Formulation and development of silymarin and piperine loaded nanoparticles with natural bioenhancer against paracetamol induced hepatotoxicity mouse model

Abstract

The proposed research study accentuates the delivery of drug and natural bioenhancer newlineby utilizing a nanoplatform based on eudragit RL (ERL) for enhanced efficacy, newlinebioavailability, synergistic effect, and minimal toxic effects. ERL was utilized to newlineencapsulate Silymarin and natural bioenhancer (Piperine) for rationally Box-Behnken newlinedesign (BBD) based development of Silymarin-piperine nanoparticles (SL-P NPs) by newlinenanoprecipitation method. The optimized SL-P NPs were 247.4±4.5 nm in size, with newline0.242±0.002 PDI and 95.92±1.01% entrapment efficiency, respectively. The surface newlinemorphology and shape were verified by SEM and TEM analysis. Differential scanning newlinecalorimetry demonstrated that the drug was successfully loaded into the NPs, and FTIR newlinevalidated polymer and drug compatibility. In vitro release studies revealed cumulative newlinedrug release of 96.16± 2.87% in phosphate buffer saline (pH 7.4) for 24 hours. We also newlineevaluated the antioxidant mechanism of silymarin, adding to our understanding of SL newlineP NPs antioxidant characteristics as compared with Silymarin, Piperine, and Vitamin newlineE. In vivo hepatoprotective evaluation of SL-P NPs in APAP intoxicated mice portrayed newlinesignificantly improved different biochemical parameters (plt0.0001) as compared to newlinethe marketed product which was further confirmed by histopathological assessment of newlinethe liver. In conclusion, the co-delivery approach of silymarin with bioenhancer was newlineproved to be beneficial and highly effective in enhancing bioavailability, solubility, and newlineliver toxicity alleviation. newline