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  • Title: Strategies for Improving Healing of the Gastric Epithelium Using Oral Solid Dispersions Loaded with Pentacyclic Triterpene-Rich Centella Extract.
    Author: Wannasarit S, Puttarak P, Kaewkroek K, Wiwattanapatapee R.
    Journal: AAPS PharmSciTech; 2019 Aug 08; 20(7):277. PubMed ID: 31396788.
    Abstract:
    The pentacyclic triterpenoid compounds in Centella asiatica extract, mainly consisting of asiaticoside (AS), asiatic acid (AA), madecassoside (MS), and madecassic acid (MA), possess wound healing and anti-ulcer properties, but their low aqueous solubility and dissolution rate are disadvantageous for oral administration. In this study, pentacyclic triterpene-rich centella extract (PRE) was combined with Eudragit® EPO as a hydrophilic polymer using solvent evaporation to produce a solid dispersion (PRE-ESD). The optimum PRE/Eudragit ratio of 1:2 enhanced the solubility and dissolution of glycosides (AS > 3.5 folds, MS > 2 folds) and aglycones (AA > 65 folds and MA > 56 folds) in 0.1 N hydrochloric acid (pH 1.2). DSC, XRD, and FT-IR analysis showed that the four pentacyclic triterpenes in PRE existed in the amorphous state in the solid dispersion. Moreover, almost 100% of the compounds were released from the solid dispersion within 2 h. The effects of PRE-ESD on cell proliferation and wound healing in vitro were investigated in human gastric epithelial cell lines (AGS cells). Exposure to PRE-ESD (equivalent to PRE concentration of 10 μg/mL) promoted cell proliferation and enhanced 'wound closure' in the scratch assay of wound healing by 82% compared with non-treated groups. Unformulated MA and AA aglycones did not exhibit a wound healing effect. Moreover, PRE-ESD was found to accelerate wound closure compared with either AS or MS, indicating that the wound healing properties of PRE-ESD are conferred by the active compounds AS and MS that are presented in PRE.
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