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可注射聚合物体系中多种生长因子的持续释放：一种新型的血管生成治疗方法。

Sustained release of multiple growth factors from injectable polymeric system as a novel therapeutic approach towards angiogenesis.

机构信息

Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio 43210-1252, USA.

出版信息

Pharm Res. 2010 Feb;27(2):264-71. doi: 10.1007/s11095-009-0014-0. Epub 2009 Dec 1.

DOI:10.1007/s11095-009-0014-0
PMID:19953308
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2812420/
Abstract

PURPOSE

The aim was to investigate that a bio-degradable alginate and poly lactide-co-glycolide (PLG) system capable of delivering growth factors sequentially would be superior to single growth factor delivery in promoting neovascularization and improving perfusion.

METHODS

Three groups of apoE null mice underwent unilateral hindlimb ischemia surgery and received ischemic limb intramuscular injections of alginate (Blank), alginate containing VEGF(165) (VEGF), or alginate containing VEGF(165) combined with PLG microspheres containing PDGF-BB (VEGF/PDGF). Vascularity in the ischemic hindlimb was assessed by morphologic and immunohistochemical end-points, while changes in blood flow were assessed by Laser Doppler Perfusion Index. Muscle VEGF and PDGF content was assessed at multiple time points.

RESULTS

In the VEGF/PDGF group, local tissue VEGF and PDGF levels peaked at week 2 and 4, respectively, with detectable PDGF levels at week 6. At week 6, mean vessel mean diameter was significantly greater in the VEGF/PDGF group compared to the VEGF or Blank groups with evidence of well-formed smooth muscle-lined arterioles.

CONCLUSIONS

Sequential delivery of VEGF and PDGF using an injectable, biodegradable platform resulted in stable and sustained improvements in perfusion. This sustained, control-released, injectable alginate polymer system is a promising approach for multiple growth factor delivery in clinical application.

摘要

目的

本研究旨在探讨一种可递呈生长因子的生物可降解藻酸盐和聚乳酸-共-乙醇酸（PLG）系统，其递呈顺序是否优于单一生长因子递呈，从而更有利于促进血管新生和改善灌注。

方法

三组载脂蛋白 E 基因敲除（apoE-/-）小鼠接受单侧后肢缺血手术，并接受藻酸盐（空白对照）、含 VEGF（165）的藻酸盐（VEGF）或含 VEGF（165）和 PDGF-BB 载 PLG 微球的藻酸盐（VEGF/PDGF）的缺血后肢肌肉内注射。通过形态学和免疫组织化学终点评估缺血后肢的血管生成情况，通过激光多普勒灌注指数评估血流变化。在多个时间点评估肌肉 VEGF 和 PDGF 含量。

结果

在 VEGF/PDGF 组中，局部组织 VEGF 和 PDGF 水平分别在第 2 周和第 4 周达到峰值，第 6 周仍可检测到 PDGF 水平。在第 6 周时，VEGF/PDGF 组的平均血管直径明显大于 VEGF 组或空白对照组，并且有形成良好的平滑肌衬里的小动脉。

结论

使用可注射的生物可降解平台递呈 VEGF 和 PDGF 的顺序给药可稳定并持续改善灌注。这种持续、控制释放的可注射藻酸盐聚合物系统是临床应用中多种生长因子递呈的一种有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/e21a0756dcb9/11095_2009_14_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/1deab3678237/11095_2009_14_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/fbbcadb6a8c9/11095_2009_14_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/cee88f061179/11095_2009_14_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/5d05cba9ac85/11095_2009_14_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/66ed76098422/11095_2009_14_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/2b30499ae4ae/11095_2009_14_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/8f785e66447d/11095_2009_14_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/0258e3aa6c7b/11095_2009_14_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/e21a0756dcb9/11095_2009_14_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/1deab3678237/11095_2009_14_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/fbbcadb6a8c9/11095_2009_14_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/cee88f061179/11095_2009_14_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/5d05cba9ac85/11095_2009_14_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/66ed76098422/11095_2009_14_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/2b30499ae4ae/11095_2009_14_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/8f785e66447d/11095_2009_14_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/0258e3aa6c7b/11095_2009_14_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ef/2812420/e21a0756dcb9/11095_2009_14_Fig9_HTML.jpg

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