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.

自微乳给药系统（SMEDDS）通常用于增强疏水性和亲脂性药物的溶解度。近年来，该技术已用于难溶性药物的开发和研究。然而，SMEDDS在体内的具体吸收机制尚未明确。在本研究中，我们制备了不同电荷的冬凌草甲素自微乳给药系统（ORI-SMEDDS）。例如，具有正zeta 电位的 ORI-SMEDDS 标记为$+$SMEDDS、ORI-SMEDDS 具有负 zeta 电位标记为$-$SMEDDS。然后对制剂进行体外脂肪分解、体外渗透和单次肠道灌注研究。这些实验的结果表明，药物在小肠中的吸收和渗透可能受到 ORI-SMEDDS 油相成分和禁食的影响。特别是，我们注意到 ORI-SMEDDS 携带的净电荷显着影响小肠中 ORI 的吸收和摄取。在药代动力学研究中，ORI-SMEDDS 延长了 ORI在体内的保留时间。与混悬液相比，+SMEDDS和-SMEDDS的相对生物利用度分别为169.65%和193.34%。总之，我们的研究证实SMEDDS的油相组成、表面电荷和肠道中的特定吸收位点是影响SMEDDS在肠道中吸收和渗透的几个因素。其中，SMEDDS的充电条件是影响体内吸收过程的主要因素。ORI-SMEDDS作为冬凌草甲素的一种替代且有前景的给药系统，在广泛的临床应用中展现出了光明的前景。