Development of small alginate microcapsules for recombinant gene product delivery to the rodent brain
Development of small alginate microcapsules for recombinant gene product delivery to the rodent brain
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开发用于将重组基因产物递送至啮齿动物大脑的小型藻酸盐微胶囊
DOI：
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
P. Chang
中科院分区：
文献类型：
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作者：
C. Ross;P. Chang
一种利用海藻酸盐微囊中的重组细胞进行基因治疗的新形式已被证明在治疗几种人类疾病的动物模型中是有效的。为了用这项技术治疗啮齿动物的神经缺陷，微囊的大小必须减小，以便植入中枢神经系统(CNS)以绕过血脑屏障。本文报道了一种适用于小鼠中枢神经系统植入的海藻酸盐微胶囊的研制。通过改变包裹方式，重组细胞可以被包裹在直径从5到2000μm的微胶囊中。根据能够通过中枢神经植入针内径500μm的最小、均匀尺寸的细胞填充的微胶囊，确定了植入的最佳尺寸为100-200μm。与中型(500-700μm)微胶囊相比，这些小胶囊紧密地结合在一起，胶囊间空间更小，导致细胞数量增加，单位体积的重组基因产物分泌率更高。与大胶囊相比，小胶囊的机械强度也有所提高。这些具有良好的体外特性的小μm微囊为进一步体内研究利用免疫隔离基因疗法向啮齿动物中枢神经系统输送重组基因产品的可行性奠定了基础。
A novel form of gene therapy using encapsulated recombinant cells in alginate microcapsules has proven effective in treating several animal models of human diseases. For treating neurological deficits in rodents with this technology, the size of the microcapsules has to be reduced for implantation in the central nervous system (CNS) to bypass the blood–brain barrier. This article reports the development of small alginate microcapsules suitable for implantation into the mouse CNS. By varying the encapsulation protocol, recombinant cells could be encapsulated in microcapsules ranging in diameter from 5 to 2000 μm. The optimal size for implantation was determined to be 100–200 μm, based on the smallest, homogeneously sized, cell-filled microcapsules that could pass the 500 μm inner diameter of a CNS-implantation needle. Compared with medium-sized (500–700 μm) microcapsules, these small microcapsules packed more tightly together with less inter-capsule space, resulting in an increased number of cells and a higher rate of recombinant gene product secretion per volume of microcapsules. The small microcapsules also displayed increased mechanical strength, compared with large microcapsules. These excellent in vitro properties of small 100–200 μm microcapsules warrant further in vivo investigation into the feasibility of using immuno-isolation gene therapy to deliver recombinant gene products to the rodent CNS.