Controlled delivery of VEGF via modulation of alginate microparticle ionic crosslinking.

Controlled delivery of VEGF via modulation of alginate microparticle ionic crosslinking.
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DOI:
10.1016/j.jconrel.2008.10.019
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发表时间:
2009-02-20
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Saltzman WM
Saltzman WM
中科院分区:
其他
文献类型:
--
作者:
Jay SM;Saltzman WM

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治疗性血管生成的临床应用受到缺乏显示血管内皮生长因子(VEGF)的受控、持续释放的可行系统的阻碍。藻酸盐已成为VEGF递送的流行材料;然而,大多数基于藻酸盐的系统提供有限的手段来控制VEGF释放速率,而不是将VEGF:藻酸盐比率降低至次优效率。本研究描述了通过使用不同的离子交联剂来控制VEGF从小(平均直径<10 μm)藻酸盐微粒中释放的方法。与Zn 2+相对于Ca 2+的交联降低了VEGF的扩散释放,并且Zn 2+或Ca 2+交联颗粒的离散群体的组合允许控制VEGF的持续释放曲线。该颗粒制剂无毒,释放后VEGF具有生物活性。这些结果表明,藻酸盐交联的离子调节是控制VEGF释放同时保持高蛋白质:聚合物比率的可行策略,所述高蛋白质:聚合物比率使得藻酸盐成为用于递送蛋白质治疗剂的有吸引力的载体。
Clinical application of therapeutic angiogenesis is hampered by a lack of viable systems that demonstrate controlled, sustained release of vascular endothelial growth factor (VEGF). Alginate has emerged as a popular material for VEGF delivery; however most alginate-based systems offer limited means to control the rate of VEGF release beyond reducing the VEGF:alginate ratio to suboptimal efficiency. This study describes methods to control the release of VEGF from small (<10 μm mean diameter) alginate microparticles via the use of different ionic crosslinkers. Crosslinking with Zn2+ versus Ca2+ reduced VEGF diffusional release and the combination of discrete populations of either Zn2+- or Ca2+-crosslinked particles allowed for control over the sustained release profiles for VEGF. The particle preparations were non-toxic and VEGF was bioactive after release. These results demonstrate that ionic modulation of alginate crosslinking is a viable strategy for controlling release of VEGF while retaining the high protein:polymer ratio that makes alginate an attractive carrier for delivery of protein therapeutics.
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