PMID- 16858650 OWN - NLM STAT- MEDLINE DCOM- 20070105 LR - 20220317 IS - 0724-8741 (Print) IS - 0724-8741 (Linking) VI - 23 IP - 8 DP - 2006 Aug TI - Heparin immobilized porous PLGA microspheres for angiogenic growth factor delivery. PG - 1835-41 AB - 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. FAU - Chung, Hyun Jung AU - Chung HJ AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea. FAU - Kim, Hong Kee AU - Kim HK FAU - Yoon, Jun Jin AU - Yoon JJ FAU - Park, Tae Gwan AU - Park TG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 0 (Amines) RN - 0 (Excipients) RN - 0 (Polymers) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 9005-49-6 (Heparin) SB - IM MH - Amines/chemistry MH - Animals MH - Excipients MH - Fibroblast Growth Factor 2/*administration & dosage/chemistry/*pharmacology MH - Heparin/*administration & dosage/*chemistry MH - Lactic Acid MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Microspheres MH - Neovascularization, Physiologic/drug effects MH - Polyglycolic Acid MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Polymers MH - Porosity EDAT- 2006/07/22 09:00 MHDA- 2007/01/06 09:00 CRDT- 2006/07/22 09:00 PHST- 2006/02/28 00:00 [received] PHST- 2006/04/13 00:00 [accepted] PHST- 2006/07/22 09:00 [pubmed] PHST- 2007/01/06 09:00 [medline] PHST- 2006/07/22 09:00 [entrez] AID - 10.1007/s11095-006-9039-9 [doi] PST - ppublish SO - Pharm Res. 2006 Aug;23(8):1835-41. doi: 10.1007/s11095-006-9039-9.