Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea.
Pharm Res. 2013 Aug;30(8):2157-65. doi: 10.1007/s11095-013-1076-6. Epub 2013 May 18.
We hypothesized that combined delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) using microsphere/hydrogel hybrid systems could enhance mature vessel formation compared with administration of each factor alone.
Hybrid delivery systems composed of alginate hydrogels and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres containing angiogenic factors were prepared. The release behavior of angiogenic factors from hybrid systems was monitored in vitro. The hybrid systems were injected into an ischemic rodent model, and blood vessel formation at the ischemic site was evaluated.
The sustained release over 4 weeks of both VEGF and Ang-1 from hybrid systems was achieved in vitro. Co-delivery of VEGF and Ang-1 was advantageous to retain muscle tissues and significantly induced vessel enlargement at the ischemic site, compared to mice treated with either VEGF or Ang-1 alone.
Sustained and combined delivery of VEGF and Ang-1 significantly enhances vessel enlargement at the ischemic site, compared with sustained delivery of either factor alone. Microsphere/hydrogel hybrid systems may be a promising vehicle for delivery of multiple drugs for many therapeutic applications.
我们假设使用微球/水凝胶混合系统联合递送血管内皮生长因子（VEGF）和血管生成素-1（Ang-1），与单独给予每种因子相比，可增强成熟血管的形成。
制备由藻酸盐水凝胶和含有血管生成因子的聚（D，L-丙交酯-共-乙交酯）（PLGA）微球组成的混合递送系统。体外监测血管生成因子从混合系统中的释放行为。将混合系统注射到缺血性啮齿动物模型中，并评估缺血部位的血管形成。
在体外实现了 VEGF 和 Ang-1 从混合系统中持续释放 4 周以上。与单独给予 VEGF 或 Ang-1 的小鼠相比，VEGF 和 Ang-1 的联合递送有利于保留肌肉组织，并显著诱导缺血部位的血管增大。
与单独持续递送任何一种因子相比，VEGF 和 Ang-1 的持续联合递送可显著增强缺血部位的血管增大。微球/水凝胶混合系统可能是用于多种治疗应用的多种药物递送的有前途的载体。
