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J Control Release. 2009 Feb 20;134(1):26-34. doi: 10.1016/j.jconrel.2008.10.019. Epub 2008 Nov 8.

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

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  • 1Department of Biomedical Engineering, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University, New Haven, CT 06520 USA.


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 microm mean diameter) alginate microparticles via the use of different ionic crosslinkers. Crosslinking with Zn(2+) versus Ca(2+) reduced VEGF diffusional release and the combination of discrete populations of either Zn(2+)- or Ca(2+)-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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