Heparin Immobilized Porous PLGA Microspheres for Angiogenic Growth Factor Delivery

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 PLGAheparin 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 T 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.

Stability of proteins encapsulated in injectable and biodegradable poly(lactide-co-glycolide)-glucose millicylinders

“…Poly (DL-lactide-co-glycolide) (PLGA) has been used successfully to deliver therapeutic peptides and proteins in a controlled-release manner (Chung et al, 2006;Cleland and Jones, 1996;Dong et al, 2006;Kang and Schwendeman, 2007;Kissel et al, 1991;Okada, 1997;Okada et al, 1988;Schwendeman et al, 1997;Tracy et al, 1999). Its biocompatibility and biodegradability are primary driving forces behind the intensive research with this polymer (Anderson and Shive, 1997;Wise et al, 1979).…”

Tissue engineering in urology

“…Heparin immobilized PLGA scaffolds loaded with bFGF showed a notable in vivo angiogenic response, while release assays displayed an initial burst followed by a sustained release over a 3-week period. 32 Finally, nanotechnology or the field of molecular self-assembly is poised to contribute to regenerative medicine in a similar fashion. Unlike many conventional polymeric molecules, self-assembling molecules can be injected as a solution into a site and then triggered to assemble through alterations in pH, ionic charge or aggregation of biomacromolecules.…”

Controlled Release Strategy Based on Biodegradable Microspheres for Neurodegenerative Disease Therapy

“…Furthermore, other growth factors also have neurotrophic function, such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO) [34,35]. Most of these neurotrophic factors are protein or glycoprotein and are suitable to prepare sustained release microspheres [22,31,[36][37][38][39]. GDNF has been used to prepare sustained release microspheres and to use for the treatment of Parkinson's disease [19,21,23,25,40].…”