Solubilization of luteolin in PVP40 solid dispersion improves inflammation-induced insulin resistance in mice

Our previous studies have confirmed that luteolin (LU) has a good therapeutic effect on obesity and its complications. However, due to its poor water solubility, the bioavailability is low with limited clinical application. Therefore, the water-soluble solid dispersions (SD) of luteolin were prepared with polyvinylpyrrolidone (PVP) (K10, K40 & K90) by solvent evaporation. The polyvinylpyrrolidone K40 (PVP40) was selected as the ideal carrier to formulate polyvinylpyrrolidone K40-luteolin solid dispersion (PVP40-LU SD), thereby the solubility of luteolin increased about 250 times compared to the pure luteolin, without changing its physical stability and activity. The crystallinity of luteolin was reduced after the formation of solid dispersion, and no strong drug-polymer interactions were observed. This prepared water-soluble luteolin inhibits the polarization of inflammatory macrophages by decreasing the expression of pro-inflammatory cytokine genes interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in vitro. Moreover, it can improve glucose tolerance and insulin sensitivity quickly after intraperitoneal injection in mice.