Abstract

Background: Biopharmaceutical properties of tubeimoside-1, a cytotoxic amphipathic cyclic bisdesmoside, were evaluated to search for the usefulness of tubeimoside-1.
Methods: Using tubeimoside-1, the solubilizing activity to itraconazole, effect on oral absorption of itraconazole in rats, stability in aqueous solution and intestinal homogenate, cytotoxicity to Caco- 2 cells, and membrane permeability across rat intestine and Caco-2 cell monolayers were evaluated. Concentrations of tubeimoside-1 were analyzed by LC-MS.
Results: The solubility of itraconazole was 38.0 μg/mL in water containing 2.5% propylene glycol. Tubeimoside-1 and hydroxypropyl-β-cyclodextrin at a concentration of 10% increased itraconazole solubility to 6.5 mg/mL and 0.72 mg/mL, respectively. In rats, coadministration of tubeimoside-1 (10%) significantly increased the oral absorption of itraconazole, however, the enhancing effect was almost half of hydroxypropyl-β-cyclodextrin (10%). Tubeimoside-1 was gradually degraded under acidic condition and in S9 fraction of intestinal mucosal homogenates. The cytotoxicity of tubeimoside-1 was observed in Caco-2 cells. The membrane permeability of tubeimoside-1 was almost negligible in rat intestine in situ and Caco-2 cell monolayers in vitro.
Conclusions: Greater solubilizing activity and biodegradability of tubeimoside-1, in addition to cytotoxicity, were observed. Further study is necessary to search for the usefulness of tubeimoside-1 as a strong solubilizer by forming inclusion complex with lipophilic compounds.