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

Add time:08/05/2019    Source:sciencedirect.com

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 (Papp) 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 Papp (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 AUC0-∞ 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.

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