Evaluation of the cytotoxicity and intestinal absorption of a self-emulsifying drug delivery system containing sodium taurocholate.

Currently, many surfactants used in self-emulsifying drug delivery systems (SMEDDS) can cause gastrointestinal mucosal irritation and systemic toxicity. In the present study, SMEDDS were loaded with pueraria flavones, using sodium taurocholate to replace polyoxyl 40 dydrogenated castor oil (Cremophor® RH 40) as the surfactant (PF-SMEDDS) to reduce the toxicity of SMEDDS using Cremophor® RH 40 as the surfactant (PF-SMEDDS). The absorption rate constants (K) and intestinal permeability coefficients (P) were measured. The effects of P-glycoprotein inhibitor (verapamil), adenosine triphosphate (ATP) inhibitor (2,4-dinitrophenol), and carrier inhibitor on K and P values in the ileum were determined. Biological safety was also evaluated. The K and P values increased for PF-solution concentrations of 200μg/ml>100μg/ml>400μg/ml in individual segments of the intestines. The results indicated that P values of PF-SMEDDS were distinctly higher than those of SMEDDS loaded with pueraria flavones using Cremophor®RH 40 as the surfactant (PF-SMEDDS) and PF-solution in four intestinal segments. However, the K values of PF-SMEDDS were higher only in the jejunum and ileum segments compared with those of PF-SMEDDS and PF-solution. The K and P values without verapamil were significantly lower than those with verapamil. 2,4-Dinitrophenol had no effect on K and P values. The K and P values of PF-SMEDDS significantly decreased after perfusing B-SMEDDS for 1h prior to the study. The cell viabilities after exposure to SMEDDS were higher than those of SMEDDS in the range of 81-324μg/ml. Lactate dehydrogenase release from cells treated with PF-SMEDDS or B-SMEDDS was significantly lower than that from cells treated with PF-SMEDDS or B-SMEDDS at surfactant concentrations of 243 and 324μg/ml. However, there were no differences with SMEDDS treatment at surfactant concentrations of 0-162μg/ml. Hence, we conclude that SMEDDS using sodium taurocholate as the surfactant can reduce the toxicity of SMEDDS, meanwhile, maintain the characteristics of SMEDDS, and enhance intestinal absorption.