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生物相容性和可生物降解的聚合物囊泡包裹血红蛋白:一种潜在的氧载体。

Biocompatible and biodegradable polymersome encapsulated hemoglobin: a potential oxygen carrier.

作者信息

Rameez Shahid, Alosta Houssam, Palmer Andre F

机构信息

Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio 43210, USA.

出版信息

Bioconjug Chem. 2008 May;19(5):1025-32. doi: 10.1021/bc700465v. Epub 2008 Apr 29.

Abstract

This work describes the development of polymersome-encapsulated hemoglobin (PEH) self-assembled from biodegradable and biocompatible amphiphilic diblock copolymers composed of poly(ethylene oxide) (PEO), poly(caprolactone) (PCL), and poly(lactide) (PLA). In the amphiphilic diblock, PEO functions as the hydrophilic block, while either PCL or PLA can function as the hydrophobic block. PEO, PCL, and PLA are biocompatible polymers, while the last two polymers are biodegradable. PEH dispersions were prepared by extrusion through 100 nm pore radii polycarbonate membranes. In this work, the encapsulation efficiency of human and bovine hemoglobin (hHb and bHb) in polymersomes was adjusted by varying the initial concentration of Hb. This approach yielded Hb loading capacities that were comparable to values in the literature that supported the successful resuscitation of hamsters experiencing hemorrhagic shock. Moreover, the Hb loading capacities of PEHs in this study can also be tailored simply by controlling the diblock copolymer concentration. In this study, typical Hb/diblock copolymer weight ratios ranged 1.2-1.5, with initial Hb concentrations less than 100 mg/mL. The size distribution, Hb encapsulation efficiency, oxygen affinity (P 50), cooperativity coefficient (n), and methemoglobin (metHb) level of these novel PEH dispersions were consistent with values required for efficient oxygen delivery in the systemic circulation. Taken together, our results demonstrate the development of novel PEH dispersions that are both biocompatible and biodegradable. These novel dispersions show very good promise as therapeutic oxygen carriers.

摘要

这项工作描述了由聚环氧乙烷(PEO)、聚己内酯(PCL)和聚丙交酯(PLA)组成的可生物降解且生物相容的两亲性二嵌段共聚物自组装形成的聚合物囊泡包裹血红蛋白(PEH)的研发过程。在两亲性二嵌段中,PEO作为亲水嵌段,而PCL或PLA均可作为疏水嵌段。PEO、PCL和PLA都是生物相容聚合物,而后两种聚合物是可生物降解的。通过100纳米孔径的聚碳酸酯膜挤出制备PEH分散体。在这项工作中,通过改变血红蛋白的初始浓度来调节聚合物囊泡中人和牛血红蛋白(hHb和bHb)的包封效率。这种方法得到的血红蛋白负载量与文献中支持成功复苏失血性休克仓鼠的值相当。此外,本研究中PEH的血红蛋白负载量也可通过控制二嵌段共聚物浓度简单地进行调整。在本研究中,典型的血红蛋白/二嵌段共聚物重量比为1.2 - 1.5,初始血红蛋白浓度低于100毫克/毫升。这些新型PEH分散体的尺寸分布、血红蛋白包封效率、氧亲和力(P50)、协同系数(n)和高铁血红蛋白(metHb)水平与体循环中有效氧输送所需的值一致。综上所述,我们的结果证明了新型PEH分散体的研发,其兼具生物相容性和生物可降解性。这些新型分散体作为治疗性氧载体显示出非常良好的前景。

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