Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
J Nanobiotechnology. 2018 Nov 14;16(1):91. doi: 10.1186/s12951-018-0418-2.
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.
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.
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.
微透析是一种有前途的动态微生物化学采样技术。然而,典型的水性灌注液在脂溶性物质的应用中受到限制。在这项研究中,我们制备了一种新型的基于微乳液(ME)的等渗灌注液(RS-ME),以提高微透析探针对脂溶性成分的回收率。
基于伪三元相图和 ME 面积的比较,选择 Kolliphor EL 和 Transcutol P 分别作为表面活性剂和助表面活性剂,重量比(Km)为 2:1,以油酸乙酯作为油相。将 ME 与 Ringer's 溶液按 1:6(v/v)的比例混合得到等渗 RS-ME。RS-ME 中 ME 的液滴尺寸分布为 78.3 ± 9.2nm,zeta 电位为-3.5 ± 0.3mV。通过微透析灌注,RS-ME 实现了较差水溶性化合物吴茱萸碱(EVO)和钌(RUT)更高的回收率,分别为 58.36 ± 0.57%和 49.40 ± 0.57%,高于 20%(v/v)PEG 400 Ringer's 溶液(RS-PEG)和 10%(v/v)乙醇 Ringer's 溶液(RS-EtOH)。体内微透析实验证实,RS-ME 比 RS-PEG 和 RS-EtOH 更有效地在透析膜周围捕获 EVO 和 RUT 分子,且扩散程度更小。
由于 RS-ME 中的脂质成分形成纳米尺寸的液滴,并且在透析膜中有限地分散,我们获得了良好的生物相容性和可靠的透析结果,而不会影响组织微环境。作为一种新型灌注液,RS-ME 为脂溶性成分的微透析采样提供了一种简单可靠的方法。