Microencapsulation of islets in PEG-amine modified alginate-poly(L-lysine)-alginate microcapsules for constructing bioartificial pancreas
Microencapsulation of islets in PEG-amine modified alginate-poly(L-lysine)-alginate microcapsules for constructing bioartificial pancreas
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DOI：
10.1016/s0922-338x(98)80059-7
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Fu, SH
中科院分区：
文献类型：
--
作者：
Chen, JP;Chu, IM;Fu, SH
将两种带正电荷的聚乙二醇（PEG）衍生物包覆在海藻酸盐-聚（L-赖氨酸）-海藻酸盐（A-P-A）微胶囊上，使其与胶囊表面带负电荷的海藻酸盐相互作用。聚合物是甲氧基聚氧乙烯胺（PEGA 1）和聚氧乙烯双（胺）（PEGA 2），它们分别在一端或两端含有带电荷的胺基，以PEG作为骨架。如在扫描电子显微镜下检查的，用PEG-胺包覆微胶囊导致比A-P-A微胶囊表面光滑得多的胶囊表面。牛血清白蛋白进入微胶囊的扩散率在PEGA 1包衣后保持不变。但扩散率下降到不到五分之一，在A-P-A微胶囊与PEGA 2涂层。通过体内研究，微囊的生物相容性也得到了改善。将微囊植入BALB/c小鼠腹腔，植入后120 d取出。对A-P-A微囊的纤维化作用是严重的，并且通过腹膜灌洗取回的胶囊聚集成簇。相比之下，表面改性的胶囊是自由流动的，没有细胞过度生长。在静态葡萄糖试验中，A-P-A-PEGA微囊内大鼠胰岛的胰岛素分泌对葡萄糖浓度的变化反应良好。将微囊化胰岛腹腔内移植到链脲佐菌素诱导的糖尿病小鼠体内，可使实验动物在无免疫抑制的情况下维持正常血糖水平长达200 d。
Two positively charged derivatives of poly(ethylene glycol) (PEG) were coated onto alginate-poly(L-lysine)-alginate (A-P-A) microcapsules by allowing them to interact them with the negatively charged alginate on the capsule surface. The polymers are methoxypolyoxyethylene amine (PEGA1) and polyoxyethylene bis(amine) (PEGA2), which contain charged amine groups at one or both ends, respectively, with PEG as the backbone. The coating of the microcapsules with PEG-amine resulted in a much smoother capsule surface than A-P-A microcapsule surfaces as examined under a scanning electron microscope. The diffusivity of bovine serum albumin into the microcapsules remained the same after PEGA1 coating. But the diffusivity decreased to less than one-fifth that in A-P-A microcapsules coated with PEGA2. The biocompatibility of the microcapsules also improved as investigated by an in vivo study. Microcapsules were implanted in the peritoneal cavity of BALB/c mice and retrieved 120 d after implantation. The fibrotic action against A-P-A microcapsules was severe and the capsules retrieved by peritoneal lavage aggregated into clusters. In contrast, the surface-modified capsules were free-flowing and free of cell overgrowth. Secretion of insulin from rat islets within A-P-A-PEGA microcapsules responded well to changes in glucose concentration in a static glucose test. Intraperitoneal transplantation of the microencapsulated islets into streptozotocin-induced diabetic mice could maintain normal blood glucose levels in test animals for up to 200 d without immunosuppression.