A novel microemulsion-based isotonic perfusate modulated by Ringer's solution for improved microdialysis recovery of liposoluble substances

Abstract

Background: Microdialysis is promising technique for dynamic microbiochemical sampling from tissues. However, the application of typical aqueous perfusates to liposoluble substances is limited. In this study, a novel microemulsion (ME)-based isotonic perfusate (RS-ME) was prepared to improve the recovery of liposoluble components using microdialysis probes. Results: Based on pseudo-ternary phase diagrams and comparisons of the ME area, Kolliphor ® EL and Transcutol ® P were selected as the surfactant and co-surfactant, respectively, with a weight ratio (Km) of 2:1 and ethyl oleate as the oil phase. The ME was mixed with Ringer's solution at a 1:6 ratio (v/v) to obtain the isotonic RS-ME. The droplet size distribution of the ME in RS-ME was 78.3 ± 9.2 nm, with a zeta potential of - 3.5 ± 0.3 mV. By microdialysis perfusion, RS-ME achieved higher recovery rates of the poorly water-soluble compounds evodiamine (EVO) and ruthenium (RUT), i.e., 58.36 ± 0.57% and 49.40 ± 0.57%, respectively, than those of 20% (v/v) PEG 400 Ringer's solution (RS-PEG) and 10% (v/v) ethanol Ringer's solution (RS-EtOH). In vivo microdialysis experiments confirmed that RS-ME captured EVO and RUT molecules around the dialysis membrane more efficiently and exhibited less spreading than RS-PEG and RS-EtOH. Conclusions: Owing to the nanosized droplets formed by lipid components in the RS-ME and the limited dispersion out of the dialysis membrane, we obtained good biocompatibility and reliable dialysis results, without affecting the tissue microenvironment. As a novel perfusate, RS-ME provides an easy and reliable approach to the microdialysis sampling of fat-soluble components.