Pharmaceutical Research

, Volume 23, Issue 8, pp 1835–1841 | Cite as

Heparin Immobilized Porous PLGA Microspheres for Angiogenic Growth Factor Delivery

  • Hyun Jung Chung
  • Hong Kee Kim
  • Jun Jin Yoon
  • Tae Gwan Park
Research Paper

Abstract

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.

Key words

angiogenesis growth factor delivery heparin PLGA porous microsphere 

Notes

Acknowledgements

This research was supported by grants from the Ministry of Commerce, Industry and Energy (10011366) and from the Ministry of Science and Technology, National Research Laboratory Program, Republic of Korea.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Hyun Jung Chung
    • 1
  • Hong Kee Kim
    • 1
  • Jun Jin Yoon
    • 1
  • Tae Gwan Park
    • 1
  1. 1.Department of Biological SciencesKorea Advanced Institute of Science and TechnologyDaejeonSouth Korea

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