Intestinal absorption studies of ORI-SMEDDS with different zeta potentials through lipolysis absorption model in vitro, single pass intestine perfusion and pharmacokinetics

Self-microemulsion drug delivery system (SMEDDS) is always applied to enhance the solubility of hydrophobic and lipophilic drugs. In recent years, the technology has been used for the development and study of insoluble drugs. However, the specific absorption mechanism of SMEDDS in vivo has not been clearly illustrated. In this study, we prepared oridonin self-microemulsion drug delivery systems (ORI-SMEDDS) with different charges. For instance, ORI-SMEDDS with positive zeta potential is marked as + SMEDDS, ORI-SMEDDS with negative zeta potential is marked as − SMEDDS. The formulations were then subjected to in vitro lipolysis, in vitro permeation, and single-pass intestinal perfusion studies. The results of these experiments showed that drug absorption and permeation in the small intestine could be affected by the composition of oil phase of ORI-SMEDDS and the presence of fasting. Particularly, we noticed that the net charge carried by ORI-SMEDDS significantly affect the absorption and uptake of ORI in the small intestine. In the pharmacokinetic studies, ORI-SMEDDS prolonged the retention of the ORI in vivo. Comparing with the suspensions, +SMEDDS and -SMEDDS presented relative bioavailability of 169.65% and 193.34%, respectively. In conclusion, our study confirmed that oil phase composition of the SMEDDS, surface charge, and the specific absorption site in the intestine are several factors that have impacts on the absorption and permeation of SMEDDS in the intestinal. Predominantly, the charging condition of SMEDDS is the main factor affecting the absorption process in vivo. ORI-SMEDDS, as an alternative and promising drug delivery system for oridonin, showed a bright future in its broad clinical application.