功能脂质体的构建及对蛋白结合类毒素清除作用的研究

肾衰竭和肝衰竭患者常存在蛋白结合类毒素(PBUTs)的蓄积，与上述人群的并发症发生和死亡率升高密切相关。由于PBUTs与白蛋白结合后形成大分子复合物，传统的血液净化技术对其清除效果欠佳，探索高效、经济、安全的新型血液净化技术具有重要临床意义。脂质体是一种由磷脂双分子层同心排列构成的空心球形颗粒，对疏水性的PBUTs亲和力较强。前期研究证实，脂质体透析液通过间接吸附原理，在体、内外实验中显著增加对PBUTs的清除效果，效果不劣于白蛋白透析。申请者拟探索影响脂质体对PBUTs清除能力的因素，并在此基础上通过调整脂质体磷脂组分、表面电势、跨膜pH梯度等，对脂质体进行功能化改性。通过超滤法、快速平衡透析实验、体外模拟透析和大鼠在体透析等技术，全面评估对各种PBUTs的清除效果和生物安全性。本项目成果将为临床上提供一种新型功能脂质体透析技术，对肝、肾功能衰竭患者具有潜在的治疗价值。

Accumulated protein-bound toxins (PBUTs) play an important role in renal or liver failure complications and are associated with increased mortality in these patients. Bound to serum albumin as large molecules, PBUTs cannot be adequately removed by current techniques of blood purification. Developing an effective, economical, and safe method for the clearance of PBUTs is of vital importance. Liposomes are hollow spherical particles that are composed of phospholipid bilayers and have a strong affinity for hydrophobic PBUTs. In previous studies, we have found that liposome-supported dialysis significantly improved the clearance of PBUTs both in vitro and in vivo on the basis of indirect adsorption and also exhibited a similar removal efficiency as albumin dialysis. In this project, we aim to identify the factors that affect the ability of the liposomes to clear PBUTs. By adjusting their physicochemical properties, such as the phospholipid compositions, surface potential, and transmembrane pH gradients, liposomes can be functionalized to provide more efficient clearing of PBUTs. In vitro binding experiments, rapid equilibrium dialysis, in vitro dialysis as well as in vivo rat dialysis will be used to evaluate the efficiency and biocompatibility of the functionalized liposomes. This project will describe a new type of dialysis technology supported by functionalized liposomes that may offer potential therapeutic values for patients with either renal or liver failure.