Gelatin hydrogel microspheres enable pinpoint delivery of basic fibroblast growth factor for the development of functional collateral vessels
Gelatin hydrogel microspheres enable pinpoint delivery of basic fibroblast growth factor for the development of functional collateral vessels
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DOI：
10.1161/01.cir.0000147779.17602.18
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发表时间：
2004-11-23
期刊：
影响因子：
37.8
通讯作者：
Nagawa, H
中科院分区：
文献类型：
--
作者：
Hosaka, A;Koyama, H;Nagawa, H
背景-各种生长因子促进侧支血管发育，被认为是治疗血管闭塞性疾病的有希望的因子。然而，尚未建立有效的药物输送系统。我们设计了一种策略，以增加功能性侧支血管通过使用酸性明胶水凝胶微球（AGHMs）纳入碱性成纤维细胞生长因子（bFGF）。本研究的目的是研究通过动脉内（IA）施用bFGF浸渍的AGHM，bFGF可以从捕获在远端小直径血管中的AGHM递送，从而诱导功能性侧支血管，并通过动脉生成过程确保血液供应。将标记的bFGF注入兔后肢缺血模型的左髂内动脉。在注射直径为10 μ m的AGHM后，不到50%的放射性在缺血后肢中累积，而在给予直径为29或59 μ m的AGHM后，在缺血肢体中计数到约80%的放射性。29 μ m直径AGHM IA给药前后即刻的小牛血压比值和双侧后肢局部血流量比值无显著变化。然后，我们评估了功能发达的侧支血管28天后，IA管理的bFGF浸渍，29微米直径AGHM。与磷酸盐缓冲盐水处理的AGHMs和肌内注射bFGF浸渍的AGHMs. Conclusions相比，bFGF浸渍的AGHMs的IA给药诱导了显著的侧支血管改善，bFGF浸渍的29-mum-直径AGHMs的IA给药强烈诱导了功能性侧支血管，而不会使缺血恶化，表明这种方法可能的治疗作用。
Background-Various growth factors promote collateral vessel development and are regarded as promising for the treatment of vascular occlusive diseases. However, an efficacious delivery system for them has yet to be established. We devised a strategy to augment functional collateral vessels by using acidic gelatin hydrogel microspheres (AGHMs) incorporating basic fibroblast growth factor ( bFGF). The aim of the present study was to investigate the hypothesis that by intra-arterial (IA) administration of bFGF-impregnated AGHMs, bFGF could be delivered from AGHMs trapped in distal small-diameter vessels and thereby induce functional collateral vessels with an assured blood supply through the process of arteriogenesis.Methods and Results-Various sizes of AGHMs (3 mg) incorporating I-125-labeled bFGF were injected into the left internal iliac artery of a rabbit model of hindlimb ischemia. Less than 50% of radioactivity accumulated in the ischemic hindlimb after injection of AGHMs that were 10 mum in diameter, whereas approximate to80% of radioactivity was counted in the ischemic limb after administration of 29- or 59-mum-diameter AGHMs. Calf blood pressure ratio and the ratio of regional blood flow of the bilateral hindlimbs immediately before and after IA administration of 29-mum-diameter AGHMs showed no significant change. Then we evaluated the function of the developed collateral vessels 28 days after IA administration of bFGF-impregnated, 29-mum-diameter AGHMs. IA administration of bFGF-impregnated AGHMs induced marked collateral vessel improvement compared with IA administration of phosphate buffered saline-treated AGHMs and intramuscular administration of bFGF-impregnated AGHMs.Conclusions-IA administration of bFGF-impregnated, 29-mum-diameter AGHMs strongly induced functional collateral vessels without worsening ischemia, indicating the possible therapeutic usefulness of this approach.