High dispersed phyto-phospholipid complex/TPGS 1000 with mesoporous silica to enhance oral bioavailability of tanshinol.

Graphical abstract Highlights • Phospholipid complex (PC) markedly improved the log P and P eff of tanshinol. • Mesoporous silica (SD) improved in vitro dissolution tanshinol from PC. • TPGS 1000 was applied for hindering the efflux of tanshinol by P-gp in DDS. • PC combined with SD was first used to enhance the oral absorption of tanshinol. • Results showed that combined DDS markedly increased the bioavailability of tanshinol. Abstract Phenolic acids are widely distributed in the plant kingdom and possess a broad spectrum of pharmacological activity. However, low oral bioavailability restricts their application. In this study, a high dispersed phyto- phospholipid complex with mesoporous silica containing TPGS 1000 (TPC-SD) was fabricated using Tanshinol (Tan) as model drug. Phospholipid complex (PC) was employed to improve the n -octanol/water partition coefficient (log P ) and apparent permeability coefficients ( P app ) of Tan. Mesoporous silica was used to compensate for the negative effects of phospholipid on drug’s dispersion and dissolution owing to its viscosity and poor water-solubility. TPGS 1000, a P-gp inhibitor, was used to block the efflux of Tan. Log P tests showed that the lipophilicity of Tan was significantly enhanced by Tanshinol phospholipid complex (TPC) formation. In vitro dissolution results showed that the cumulative dissolution percentage of Tan from TPC-SD was 4.33- fold of that from TPC in 120 min A Caco-2 permeability test confirmed that P app (AP-BL) of TPC and TPC-SD increased approximately 2.22- and 3.53- fold compared to those of unformulated Tan, respectively ( p < 0.01, p < 0.01). Pharmacokinetic studies demonstrated that the AUC 0-∞ of TPC-SD was 2.23- and 1.47- fold compared with those of unformulated Tan and TPC, respectively ( p < 0.01, p < 0.01). These results indicated that the high dispersed phyto- phospholipid complex/TPGS 1000 by mesoporous silica can be a promising drug delivery system to improve the oral bioavailability of free phenolic acids. [ABSTRACT FROM AUTHOR]