Improving the in vivo bioavailability and in vitro anti-inflammatory activity of tanshinone IIA by alginate solid dispersion

Abstract

Tanshinone IIA (TA) is a major active ingredient of traditional Chinese medicine Salvia miltiorrhiza Bunge (Danshen) with poor solubility. The strong crystallinity of TA is the main reason for its poor solubility. Since sodium alginate (SA) can suppress the drug crystal growth and has excellent biocompatibility, we hypothesize that SA may be an ideal matrix for preparing solid dispersion (SD) to improve the dissolution rate and bioavailability of TA. In this study, a novel TA-SA-SD was developed via a rapid one-pot approach for improving the dissolution rate, in vivo bioavailability, and pharmacological activity of TA. The results of scanning electron microscopy (SEM), X-ray diffraction (XRD) confirmed the SD process will reduce the crystallinity of TA. The crystallinity reduction of TA in TA-SA-SD can obviously improve the dissolution rate, oral absorption rate and in vivo bioavailability, the relative bioavailability of TA-SA-SD (1:6) and TA-SA-SD (1:8) were 2.08 and 2.75 folds of TA, respectively. In vitro anti-inflammatory assays were performed in RAW264.7 cells by ELISA, fluorescence microscope and Western blot analysis. The results revealed that the TA-SA-SD can significantly improve the pharmacological activity of TA. This study provides a successful method of incorporating hydrophobic drugs into hydrophilic bio-macromolecules matrices for improving the dissolution rate and bioavailability.