Controlled delivery of VEGF via modulation of alginate microparticle ionic crosslinking.
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.
Jay
Steven M
SM
Department of Biomedical Engineering, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University, New Haven, CT 06520 USA.
Saltzman
W Mark
WM
D000464:Alginates / Q000138:chemical synthesis* / Q000633:toxicity; D002412:Cations / Q000138:chemical synthesis* / Q000633:toxicity; D002470:Cell Survival; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000633:toxicity; D004058:Diffusion; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D020723:Glucuronic Acid / Q000138:chemical synthesis / Q000633:toxicity; D006603:Hexuronic Acids / Q000138:chemical synthesis / Q000633:toxicity; D006801:Humans; D008863:Microspheres; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology*
D000464:Alginates; D002412:Cations; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D042461:Vascular Endothelial Growth Factor A; D020723:Glucuronic Acid