Controlled delivery of VEGF via modulation of alginate microparticle ionic crosslinking

JOURNAL OF CONTROLLED RELEASE

卷:134

Article

Jay, Steven M.¹  Saltzman, W. Mark¹ 

[1] Yale Univ, Dept Biomed Engn, Interdept Program Vasc Biol & Therapeut, New Haven, CT 06511 USA

关键词: VEGF;    Protein drug delivery;    Therapeutic angiogenesis;    Controlled release;    Microparticles;   

DOI  :  10.1016/j.jconrel.2008.10.019

来源: Elsevier

【 摘 要 】

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 pm 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. (c) 2008 Elsevier B.V. All rights reserved.

【 授权许可】

Free