Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
J Control Release. 2013 Apr 28;167(2):109-19. doi: 10.1016/j.jconrel.2013.01.036. Epub 2013 Feb 10.
Despite the widespread use of drug eluting stents (DES), in-stent restenosis (ISR), delayed arterial healing and thrombosis remain important clinical complications. Gene-eluting stents (GES) represent a potential strategy for the prevention of ISR by delivering a therapeutic gene via a vector from the stent surface to the vessel wall. To this end, a model in vitro system was established to examine whether cationic liposomes could be used for gene delivery to human artery cells. Three different formulations were compared (DOTMA/DOPE, DDAB/DOPE or DDAB/POPC/Chol) to examine the effects of different cationic and neutral lipids on the transfection efficiency of lipoplex-coatings of metal surfaces. Upon completion of the characterization and optimization of the materials for gene delivery in vitro, these coatings were examined on a range of stents and deployed in a rabbit iliac artery injury model in vivo. Maximal transfection efficiencies for all coatings were observed on day 28, followed by declining, but persisting gene expression 42 days after stent placement, thereby, presenting liposomal coatings for gene eluting stents as treatment options for clinical complications associated with stenting procedures.
尽管药物洗脱支架（DES）的应用广泛，但支架内再狭窄（ISR）、延迟的动脉愈合和血栓形成仍然是重要的临床并发症。基因洗脱支架（GES）通过支架表面的载体将治疗基因递送至血管壁，代表了预防 ISR 的一种潜在策略。为此，建立了一个体外模型系统，以研究阳离子脂质体是否可用于向人动脉细胞进行基因传递。比较了三种不同的配方（DOTMA/DOPE、DDAB/DOPE 或 DDAB/POPC/Chol），以研究不同阳离子和中性脂质对金属表面脂质体涂层转染效率的影响。在完成了体外基因传递用材料的特性描述和优化后，在一系列支架上对这些涂层进行了检查，并在体内兔髂动脉损伤模型中进行了部署。所有涂层的最大转染效率均在第 28 天观察到，随后在支架放置后 42 天下降，但仍持续表达基因，从而为基因洗脱支架的脂质体涂层提供了治疗与支架置入术相关并发症的选择。
