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.

Metformin hydrochloride enteric-coated capsule (MH-EC) is a commonly used clinical drug for the treatment of type 2 diabetes. In this study, we described a metformin hydrochloride mucosal nanoparticles enteric-coated capsule (MH-MNPs-EC) based on metformin hydrochloride chitosan mucosal nanoparticles (MH-CS MNPs) and its preparation method to improve the bioavailability and hypoglycemic effect duration of MH-EC. In intestinal adhesion study, the residue rates of free drugs and mucosal nanoparticles were 10.52% and 67.27%, respectively after cleaned with PBS buffer. MH-CS MNPs could significantly improve the efficacy of MH and promote the rehabilitation of diabetes rats. In vitro release test of MH-MNPs-EC showed continuous release over 12 h, while commercial MH-EC released completely within about 1 h in intestinal environment (pH 6.8). Pharmacokinetic study was performed in beagle dogs compared to the commercial MH-EC. The durations of blood MH concentration above 2 μg/mL were 9 h for MH-MNPs-EC versus 2 h for commercial MH-EC. The relative bioavailability of MH-MNPs-EC was determined as 185.28%, compared with commercial MH-EC. In conclusion, MH-CS MNPs have good intestinal adhesion and can significantly prolong the residence time of MH in the intestine. MH-MNPs-EC has better treatment effect compared with MH-EC, and it is expected to be a potential drug product for the treatment of diabetes because of its desired characteristics.