Linoleic acid-modified liposomes for the removal of protein-bound toxins: An in vitro study
Linoleic acid-modified liposomes for the removal of protein-bound toxins: An in vitro study
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用于去除蛋白质结合毒素的亚油酸修饰脂质体：一项体外研究
DOI：
10.1177/0391398820968837
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发表时间：
2020-11-02
影响因子：
1.7
通讯作者：
Ding, Feng
中科院分区：
文献类型：
--
作者：
Shen, Yue;Shen, Yuqi;Ding, Feng
简介：蛋白结合尿毒症毒素（PBUT）和肝功能衰竭相关胆汁淤积性溶质分别与慢性肾病（CKD）和肝功能衰竭患者的不良结局相关，并且不易通过传统透析治疗清除。我们构建了亚油酸修饰的脂质体（LA-脂质体）作为透析液中的间接吸附剂，并评价了它们对代表性PBUT和胆汁淤积溶质清除的影响。方法：采用薄膜水合法制备LA脂质体。超滤柱检测脂质体与蛋白结合溶质的结合率。使用非电流和电流装置进行体外透析实验，以测定由LA-脂质体支持的透析液的清除效率。结果：LA脂质体对PBUT、胆红素和胆汁酸具有良好的结合性能。LA-脂质体透析液的代表性PBUT和胆汁淤积性溶质的溶质减少率高于传统透析液或未改性普通脂质体支持的透析液。此外，白蛋白结合的PBUT显着抑制通过添加亚油酸（LA），和去除效率大大提高了由间接吸附LA-脂质体和LA的组合作为竞争性置换剂的PBUT。结论：LA-脂质体对典型PBUT和肝功能衰竭相关溶质有较好的清除作用。此外，间接吸附LA-脂质体和竞争性置换剂的组合表明了极高结合溶质的潜在应用。
Introduction: Protein-bound uremic toxins (PBUTs) and liver failure-related cholestatic solutes are associated with adverse outcomes in patients with chronic kidney disease (CKD) and liver failure, respectively, and are not easily removed by traditional dialysis therapies. We constructed linoleic acid-modified liposomes (LA-liposomes) as indirect adsorbent in the dialysate, and evaluated their effects on the clearance of the representative PBUTs and cholestatic solutes. Methods: The LA-liposomes were prepared by the thin-film hydration method. The binding rates of liposomes and protein-bound solutes were detected by the ultrafiltration column. The in vitro dialysis experiments were performed using both non-current and current devices to assay the clearing efficiency of the dialysate supported by LA-liposomes. Results: The LA-liposomes exhibited good binding properties to the PBUTs, bilirubin and bile acids. The LA-liposome dialysate showed higher solute reduction rates of the representative PBUTs and cholestatic solutes than the traditional dialysate or dialysate supported by the unmodified plain liposomes. Also, albumin binding of the PBUTs was significantly inhibited by the addition of linoleic acid (LA), and the removal efficiency of PBUTs was greatly enhanced by the combination of indirect adsorbent LA-liposomes and LA as the competitive displacer. Conclusion: LA-liposomes were efficient in the clearance of the representative PBUTs and liver failure-related solutes. Moreover, the combination of indirect adsorbent LA-liposomes and competitive displacer suggested a potential application for the extremely highly-bound solutes.