Kulkarni Mangesh, Breen Ailish, Greiser Udo, O'Brien Timothy, Pandit Abhay
Network of Excellence for Functional Biomaterials and Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
Biomacromolecules. 2009 Jun 8;10(6):1650-4. doi: 10.1021/bm900248n.
Nonviral gene delivery via natural biomacromolecules show great promise as controlled release systems while avoiding the associated drawbacks with viral gene delivery such as immunogenicity and safety issues. Here, a fibrin-lipoplex system for topical delivery of multiple genes is described. In vitro release analysis showed efficient retention of the lipoplexes in the fibrin scaffold. The biomolecular interaction between fibrinogen and liposomes was investigated qualitatively using surface plasmon resonance. The strong binding between the lipoplexes and the fibrinogen component of the scaffold was observed and that could explain the in vitro release profile observed in our studies. Both in vitro and in vivo transfection studies using multiple reporter genes were performed to establish the bioactivity of released lipoplexes. The ability of the lipoplexes to transfect fibroblasts in vitro was shown to be maintained even after extended periods of encapsulation within the scaffold. Furthermore, in a rabbit ear ulcer model, the fibrin-lipoplex system was shown to have significantly higher transfection efficiency for two reporter genes at day 7 when compared to lipoplexes alone, suggesting that this fibrin-lipoplex system is suitable for extended release of lipoplexes for topical gene delivery applications.
通过天然生物大分子进行的非病毒基因递送作为控释系统显示出巨大的前景，同时避免了病毒基因递送相关的缺点，如免疫原性和安全性问题。在此，描述了一种用于局部递送多种基因的纤维蛋白-脂质体复合物系统。体外释放分析表明脂质体在纤维蛋白支架中有效保留。使用表面等离子体共振定性研究了纤维蛋白原与脂质体之间的生物分子相互作用。观察到脂质体与支架的纤维蛋白原成分之间有强烈结合，这可以解释我们研究中观察到的体外释放情况。使用多个报告基因进行了体外和体内转染研究，以确定释放的脂质体的生物活性。结果表明，即使在支架内长时间包封后，脂质体在体外转染成纤维细胞的能力仍得以维持。此外，在兔耳溃疡模型中，与单独的脂质体相比，纤维蛋白-脂质体复合物系统在第7天时对两个报告基因的转染效率显著更高，这表明该纤维蛋白-脂质体复合物系统适用于脂质体的缓释，用于局部基因递送应用。
