Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor-1.

Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor-1.
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DOI:
10.1002/jbm.a.32883
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发表时间:
2010-11
影响因子:
4.9
通讯作者:
Brey, Eric M.
Brey, Eric M.
中科院分区:
工程技术3区
文献类型:
--
作者:
Khanna, Omaditya;Moya, Monica L.;Opara, Emmanuel C.;Brey, Eric M.

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研究了用选择性渗透的聚-L-鸟氨酸(PLO)膜包覆的藻酸盐微胶囊用于胰岛的包封和移植作为1型糖尿病的治疗。这种方法的治疗潜力可以通过局部刺激微血管网络来提高,以满足包封细胞的质量运输需求。成纤维细胞生长因子-1(FGF-1)是一种有效的血管生成因子,当其以持续的方式递送时具有最佳效果。在本文中,描述了一种技术,用于生成多层藻酸盐微胶囊,其具有可用于递送FGF-1的外藻酸盐层。研究了藻酸盐浓度和组成(高甘露糖醛酸(M)或古罗糖醛酸(G)含量)对外层尺寸和稳定性、蛋白质包封效率和释放动力学的影响。该技术产生稳定的藻酸盐外层,平均厚度在113-164 μm之间,随着藻酸盐浓度和G含量增加。外层能够包封并释放FGF-1长达30天,其中1.25%的高G藻酸盐显示出最持续的释放。释放的FGF-1在肝素存在下保留其生物活性,并且外层的添加没有改变PLO涂层的选择性渗透性。该技术可用于产生包封系统,其递送蛋白质以刺激包封的胰岛周围的局部新血管形成。
Alginate microcapsules coated with a permselective poly-L-ornithine (PLO) membrane have been investigated for the encapsulation and transplantation of islets as a treatment for type 1 diabetes. The therapeutic potential of this approach could be improved through local stimulation of microvascular networks in order to meet mass transport demands of the encapsulated cells. Fibroblast growth factor-1 (FGF-1) is a potent angiogenic factor with optimal effect occurring when it is delivered in a sustained manner. In this paper, a technique is described for the generation of multilayered alginate microcapsules with an outer alginate layer that can be used for the delivery of FGF-1. The influence of alginate concentration and composition (high mannuronic acid (M) or guluronic acid (G) content) on outer layer size and stability, protein encapsulation efficiency, and release kinetics was investigated. The technique results in a stable outer layer of alginate with a mean thickness between 113–164 µm, increasing with alginate concentration and G-content. The outer layer was able to encapsulate and release FGF-1 for up to thirty days, with 1.25% of high G alginate displaying the most sustained release. The released FGF-1 retained its biologic activity in the presence of heparin, and the addition of the outer layer did not alter the permselectivity of the PLO coat. This technique could be used to generate encapsulation systems that deliver proteins to stimulate local neovascularization around encapsulated islets.
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