Phospholipid Complex-loaded Self-assembled Phytosomal Soft Nanoparticles: Evidence of Enhanced Solubility, Dissolution Rate, Ex Vivo Permeability, Oral Bioavailability, and Antioxidant Potential of Mangiferin

In this study, self-assembled phytosomal soft nanoparticles encapsulated with phospholipid complex (MPLC SNPs) using a combination of solvent evaporation and nanoprecipitation method were developed to enhance the biopharmaceutical and antioxidant potential of MGN. The mangiferin-Phospholipon® 90H complex (MPLC) was produced by the solvent evaporation method and optimized using central composite design (CCD). The optimized MPLC was converted into MPLC SNPs using the nanoprecipitation method. The physicochemical and functional characterization of MPLC and MPLC SNPs was carried out by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FT-IR), powder X-ray diffractometer (PXRD), proton nuclear magnetic resonance (H-NMR), solubility, in vitro dissolution, oral bioavailability, and in vivo antioxidant studies. A CCD formed stable MPLC with the optimal values of 1:1.76, 50.55 °C, and 2.02 h, respectively. Characterization studies supported the formation of a complex. MPLC and MPLC SNPs both enhanced the aqueous solubility (~ 32-fold and ~ 39-fold), dissolution rate around ~ 98% via biphasic release pattern, and permeation rate of ~ 97%, respectively, compared with MGN and MGN SNPs. Liver function tests and in vivo antioxidant studies exhibited that MPLC SNPs significantly preserved the CCl-intoxicated liver marker and antioxidant marker enzymes, compared with MGN SNPs. The oral bioavailability of MPLC SNPs was increased appreciably up to ~ 10-fold by increasing the main pharmacokinetic parameters such as C, T, and AUC. Thus, MPLC SNPs could be engaged as a nanovesicle delivery system for improving the biopharmaceutical and antioxidant potential of MGN. Graphical abstract.