Rationally designed nanoparticulate delivery approach for silymarin with natural bio-enhancer: In vitro characterization and in vivo evaluations of hepatoprotective effects in a mouse model

The proposed research study accentuates the delivery of drug and natural bioenhancer by utilizing a nanoplatform based on eudragit RL (ERL) for enhanced efficacy, bioavailability, synergistic effect, and minimal toxic effects. ERL was utilized to encapsulate Silymarin and natural bioenhancer (Piperine) for rationally BoxBehnken design (BBD) based development of Silymarin-piperine nanoparticles (SL-P NPs) by nanoprecipitation method. The optimized SL-P NPs were 247.4 & PLUSMN; 4.5 nm in size, with 0.242 & PLUSMN; 0.002 PDI and 95.92 & PLUSMN; 1.01% entrapment efficiency, respectively. The surface morphology and shape were verified by SEM and TEM analysis. Differential scanning calorimetry demonstrated that the drug was successfully loaded into the NPs, and FTIR validated polymer and drug compatibility. In vitro release studies revealed cumulative drug release of 96.16 & PLUSMN; 2.87% in phosphate buffer saline (pH 7.4) for 24 h. We also evaluated the antioxidant mechanism of silymarin, adding to our understanding of SL-P NPs' antioxidant characteristics as compared with Silymarin, Piperine, and Vitamin E. In vivo hepatoprotective evaluation of SL-P NPs in APAP-intoxicated mice portrayed significantly improved different biochemical parameters (p < 0.0001) as compared to the marketed product which was further confirmed by histopathological assessment of the liver. In conclusion, the co-delivery approach of silymarin with bioenhancer was proved to be beneficial and highly effective in enhancing bioavailability, solubility, and liver toxicity alleviation.