Heparin immobilized porous PLGA microspheres for angiogenic growth factor delivery

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Purpose. Heparin immobilized porous poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared for sustained release of basic fibroblast growth factor ( bFGF) to induce angiogenesis. Materials and Methods. Porous PLGA microspheres having primary amine groups on the surface were prepared using an oil-in-water (O/W) single emulsion method using Pluronic F-127 as an extractable porogen. Heparin was surface immobilized via covalent conjugation. bFGF was loaded into the heparin functionalized (PLGA-heparin) microspheres by a simple dipping method. The bFGF loaded PLGA-heparin microspheres were tested for in vitro release and in vivo angiogenic activity. Results. PLGA microspheres with an open-porous structure were formed. The amount of conjugated amine group onto the microspheres was 1.93 +/- 0.01 nmol/mg-microspheres, while the amount of heparin was 95.8 pmol/mg-microspheres. PLGA-heparin microspheres released out bFGF in a more sustained manner with a smaller extent of initial burst than PLGA microspheres, indicating that surface immobilized heparin controlled the release rate of bFGF. Subcutaneous implantation of bFGF loaded PLGA-heparin microspheres in mice significantly induced the formation of new vascular microvessels. Conclusions. PLGA microspheres with an open porous structure allowed significant amount of heparin immobilization and bFGF loading. bFGF loaded PLGA-HP microspheres showed sustained release profiles of bFGF in vitro, demonstrating reversible and specific binding of bFGF to immobilized heparin. They also induced local angiogenesis in vivo in an animal model.
Publisher
SPRINGER/PLENUM PUBLISHERS
Issue Date
2006-08
Language
English
Article Type
Article
Keywords

LASER-SCANNING MICROSCOPY; RELEASE; SURFACE; MICROPARTICLES; ARTERIOGENESIS; MICROCAPSULES; SCAFFOLDS; MATRICES; HORMONE

Citation

PHARMACEUTICAL RESEARCH, v.23, no.8, pp.1835 - 1841

ISSN
0724-8741
DOI
10.1007/s11095-006-9039-9
URI
http://hdl.handle.net/10203/13175
Appears in Collection
NT-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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