Improved poly(d,l-lactide-co-1,3-trimethylene carbonate)6 copolymer microparticle vehicles for sustained and controlled delivery of bioactive basic fibroblast growth factor

Abstract

A novel, biocompatible and biodegradable six-arm branched copolymer poly(d,l-lactide)-co-(1,3-trimethylene carbonate)6 has been synthesized and fabricated as a porous microparticle with an oil-in-water single emulsion method. Poly(d,l-lactide-co-1,3-trimethylene carbonate)6 microparticles were further conjugated with heparin by 1-ethyl-3-3-dimethylamino-propylcarbodiimide/ N-hydroxysuccinimide chemistry and characterized using 1H-nuclear magnetic resonance and scanning electron microscopy. The heparin-loading capacity of poly(d,l-lactide-co-1,3-trimethylene carbonate)6 microparticles was identified as 213 ± 6 pmol/mg-particle determined with toluidine blue method. The resultant binding efficiency and release profile of basic fibroblast growth factor which is bound on heparin–poly(d,l-lactide-co-1,3-trimethylene carbonate)6 microparticles were quantitatively analyzed by enzyme-linked immunosorbent assay. Thus, the developed poly(d,l-lactide-co-1,3-trimethylene carbonate)6 porous microparticles presented superior capacity of growth factor cargo as 1965 ± 117 pg basic fibroblast growth factor per mg-microparticles and displayed a sustained release profile over 4 weeks with quite low initial burst. Additionally, the viability of dissociated basic fibroblast growth factor was confirmed with methylthiazolyltetrazolium quantitative assay along with in vitro culturing model of rodent neural stem cell. Collectively, our results demonstrate that heparin–poly(d,l-lactide-co-1,3-trimethylene carbonate)6 microparticles attained controllable and sustained delivery of bioactive basic fibroblast growth factor for 4 weeks with significantly reduced burst release. The present heparin–poly(d,l-lactide-co-1,3-trimethylene carbonate)6 porous microparticulate system could be potentially developed to foster a novel bioengineering platform for repair and regeneration of injured nervous system.