A Temporal Gene Delivery System Based on Fibrin Microspheres
A Temporal Gene Delivery System Based on Fibrin Microspheres
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DOI：
10.1021/mp100295z
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发表时间：
2011-03-01
影响因子：
4.9
通讯作者：
Pandit, Abhay
中科院分区：
文献类型：
--
作者：
Kulltarni, Mangesh M.;Greiser, Udo;Pandit, Abhay
将组织工程支架和脂质体等互补的非病毒基因传递载体结合起来，不仅为开发安全有效的基因传递系统提供了一条有前途的途径，而且为设计具有时空控制的动态缓释系统提供了机会。然而，诸如纤维蛋白的支架的DNA负载能力是有限的。携带DNA复合物的纤维蛋白微球可用于扩展纤维蛋白支架的容量。在这里，在概念研究的证明中，描述了纤维蛋白微球用于延长基因递送能力的可行性。为了实现这一目标，纤维蛋白微球封装lipoplex制造。以内皮型一氧化氮合酶（eNOS）为模型基因，在兔耳溃疡创面愈合不良模型中，通过凝胶电泳和体内初步研究，分别评估了DNA的结构和功能完整性。结果证实了结构完整性和成功的交付和功能完整性，通过eNOS的血管生成作用进行定性评估。最后，作为朝向开发“纤维蛋白中的纤维蛋白”暂时释放系统的一步，纤维蛋白微球显示出与纤维蛋白支架相比差异地降解和释放DNA。因此可以得出结论，纤维蛋白微球可以用于基因递送以扩展纤维蛋白支架的容量，并且可以形成“纤维蛋白中的纤维蛋白”暂时释放系统的组分，
Combining complementary nonviral gene delivery vehicles such as tissue engineering scaffolds and liposomes not only is a promising avenue for development of safe and effective gene delivery system but also provides, an opportunity to design dynamic extended release systems with spatiotemporal control. However, the DNA loading capacity of scaffolds such as fibrin is limited. Fibrin microspheres carrying DNA complexes can be utilized to extend the capacity of fibrin scaffold. Here, in a proof of concept study, the feasibility of fibrin microspheres for extending gene delivery capacity is described. Toward this goal, fibrin microspheres encapsulating lipoplexes were fabricated. The structural and functional integrity of DNA was assessed respectively by gel electrophoresis and an in vivo pilot study, using endothelial nitric oxide synthase (eNOS) as a model therapeutic gene in a rabbit ear ulcer model of compromised wound healing. The results confirmed structural integrity and successful delivery and functional integrity, assessed qualitatively by angiogenic effect of eNOS. Finally, as a step toward development of a "fibrin in fibrin" temporal release system, fibrin microspheres were shown to degrade and release DNA differentially compared to fibrin scaffold. It can thus be concluded that fibrin microspheres can be utilized for gene delivery to extend the capacity of a fibrin scaffold and can form a component of a "fibrin in fibrin" temporal release system,