Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
Mol Pharm. 2011 Apr 4;8(2):439-46. doi: 10.1021/mp100295z. Epub 2011 Jan 12.
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.
将互补的非病毒基因传递载体（如组织工程支架和脂质体）结合起来不仅是开发安全有效的基因传递系统的有前途的途径，而且还为设计具有时空控制的动态延长释放系统提供了机会。然而，支架（如纤维蛋白）的 DNA 负载能力有限。携带 DNA 复合物的纤维蛋白微球可用于延长纤维蛋白支架的容量。在这里，在概念验证研究中，描述了纤维蛋白微球用于扩展基因传递能力的可行性。为此，制备了包封脂质体的纤维蛋白微球。通过凝胶电泳和体内初步研究分别评估 DNA 的结构和功能完整性，以内皮型一氧化氮合酶（eNOS）作为模型治疗基因，在兔耳溃疡模型中评估创伤愈合受损时的治疗效果。结果证实了结构完整性和成功传递以及功能完整性，通过 eNOS 的血管生成作用进行定性评估。最后，作为开发“纤维蛋白中的纤维蛋白”时间释放系统的一步，与纤维蛋白支架相比，纤维蛋白微球显示出不同的降解和释放 DNA 的能力。因此，可以得出结论，纤维蛋白微球可用于基因传递以扩展纤维蛋白支架的容量，并可成为“纤维蛋白中的纤维蛋白”时间释放系统的组成部分。
