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脂质体支持的酶促腹膜透析。

Liposome-supported enzymatic peritoneal dialysis.

机构信息

Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland.

Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland.

出版信息

Biomaterials. 2017 Nov;145:128-137. doi: 10.1016/j.biomaterials.2017.08.016. Epub 2017 Aug 14.

Abstract

Compared to hemodialysis, peritoneal dialysis represents a more straightforward and less invasive alternative, though current solutions are not as effective. Herein, the feasibility of liposome-supported enzymatic peritoneal dialysis (LSEPD) is explored to increase the functionality of peritoneal dialysis for the model indication acute alcohol poisoning. Enzyme-loaded liposomes (E-Liposomes) containing alcohol metabolizing enzymes, alcohol oxidase and catalase, are developed and their in vitro and in vivo performances investigated. The E-Liposomes outperform the free enzymes in stability, overcoming the thermal instability of alcohol oxidase and enhancing the in vitro ethanol elimination, which is further accelerated by hydrogen peroxide, due to the rapid generation of oxygen by catalase. Compared to the free enzymes, the E-Liposomes exhibit reduced systemic exposure and organ distribution. In a rodent ethanol intoxication model, LSEPD enhances ethanol metabolism as evidenced by an increased acetaldehyde production, ethanol's primary metabolite. In conclusion, LSEPD presents an innovative platform to temporarily enhance xenobiotic metabolism, in view of the improved enzyme stability and peritoneal retention.

摘要

与血液透析相比,腹膜透析是一种更直接、侵入性更小的替代方法,但目前的解决方案效果并不理想。本文探讨了脂质体支持的酶促腹膜透析(LSEPD)的可行性,以提高腹膜透析在急性酒精中毒模型指示中的功能。开发了含有酒精代谢酶、酒精氧化酶和过氧化氢酶的载酶脂质体(E-Liposomes),并研究了它们的体外和体内性能。E-Liposomes 在稳定性方面优于游离酶,克服了酒精氧化酶的热不稳定性,并通过过氧化氢增强了体外乙醇消除,这由于过氧化氢酶快速产生氧气而进一步加速。与游离酶相比,E-Liposomes 表现出较低的全身暴露和器官分布。在啮齿动物乙醇中毒模型中,LSEPD 通过增加乙醛(乙醇的主要代谢物)的产生来增强乙醇代谢。总之,鉴于酶的稳定性和腹膜保留得到改善,LSEPD 为暂时增强外源性物质代谢提供了一个创新平台。

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