Water Soluble Polymers for Immunoisolation II: Evaluation of Multicomponent Microencapsulation Systems

Water Soluble Polymers for Immunoisolation II: Evaluation of Multicomponent Microencapsulation Systems
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用于免疫隔离的水溶性聚合物 II:多组分微胶囊系统的评估

DOI:
10.1007/3-540-69682-2_2
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发表时间:
1998
影响因子:
--
通讯作者:
Taylor G. Wang
Taylor G. Wang
中科院分区:
化学4区
文献类型:
--
作者:
A. Prokop;D. Hunkeler;A. Powers;R. Whitesell;Taylor G. Wang

文献摘要

被引文献

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通过复凝聚反应从聚阴离子和聚阳离子混合物制备微胶囊。合成的、半合成的和天然存在的大分子的多组分共混物已经被评估,特别关注胰岛免疫隔离屏障的制备。筛选产生了33种聚合物系统,根据其机械强度、胶囊特性(如形状、表面光滑度、稳定性和溶胀/收缩)和渗透性(MWCO)对其进行了比较。还对聚合物混合物存在下的细胞活力进行了有限数量的测试。这些包括测量包囊胰岛的灌注和宿主组织反应。观察到所生产的膜的质量是聚合物性质、加工条件(例如简单电解质的类型和浓度)和反应时间的强函数。此外,开发了基于形成囊状“壁复合物”的多组分膜分离技术,用于同时优化膜的机械性能和渗透性。这涉及通过核心聚阴离子与小离子型离子的反应制备宽孔基质。随后在第二反应阶段添加第二种低分子量或中分子量聚阳离子,其随时间扩散到胶囊中可用于控制膜壁厚度和渗透性。或者,同时应用低分子量阳离子和高分子量阳离子(或二价阳离子和多价阳离子)通常导致具有类似可控性质的胶囊。对于许多组合,观察到明显的囊壁。总体而言,7种化学物质被确定为提供合适的渗透性和囊机械性能。所有这些都含有阴离子多糖共混物内部的低聚阳离子溶液。发现藻酸盐/硫酸纤维素//聚亚甲基-共-胍/氯化钙/氯化钠系统是标准藻酸盐-聚赖氨酸-藻酸盐胶囊(阿帕)的最可行的替代物。
Microcapsules have been prepared via a complex coacervation reaction from polyanion and polycation mixtures. Multicomponent blends of synthetic, semi-synthetic and naturally occurring macromolecules have been evaluated with a particular interest in the preparation of immunoisolation barriers for pancreatic islets. A screening has resulted in thirty three polymeric systems which have been compared according to their mechanical strength, capsule characteristics (such as shape, surface smoothness, stability, and swelling/shrinking) and permeability (MWCO). A limited number of tests were also carried out on the cell viability in the presence of polymer mixtures. These included measurements of the perifusion of encapsulated pancreatic islets and the host tissue response. The quality of the membrane produced was observed to be a strong function of the polymer properties, processing conditions, such as the type and concentration of the simple electrolyte, and the reaction time. Additionally, a multicomponent polyelectrolyte technology based on the formation of a capsular “wall-complex” was developed for the simultaneous optimization of the membrane mechanical properties and permeability. This involved the preparation of a wide pore matrix through the reaction of a core polyanion with a small ionotropic ion. A second, low or medium molecular weight, polycation was subsequently added, in a second reactive stage, and its time dependent diffusion into the capsule could be used to control the membrane wall thickness and permeability. Alternatively, the simultaneous application of low and high molecular weight cations (or a divalent and polyvalent cation) often led to capsules with similar controllable properties. For many combinations, a distinct capsular wall was observed. Overall seven chemistries were identified as providing suitable permeability and capsular mechanical properties. All contained an anionic polysaccharide blend interior to an oligocation solution. The alginate/cellulose sulfate//polymethylene-co-guanidine/calcium chloride/sodium chloride system was found to be the most viable alternative to the standard alginate-polylysine-alginate capsule (APA).