Heparin immobilized porous PLGA microspheres for angiogenic growth factor delivery.
OBJECTIVE
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.


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.
Chung
Hyun Jung
HJ
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Kim
Hong Kee
HK
Yoon
Jun Jin
JJ
Park
Tae Gwan
TG
D000588:Amines / Q000737:chemistry; D000818:Animals; D005079:Excipients; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D006493:Heparin / Q000008:administration & dosage* / Q000737:chemistry*; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D016062:Porosity
D000588:Amines; D005079:Excipients; D011108:Polymers; D016222:Fibroblast Growth Factor 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006493:Heparin