Effect of encapsulation or grafting on release kinetics of recombinant human bone morphogenetic protein-2 from self-assembled poly(lactide-co-glycolide ethylene oxide fumarate) nanoparticles.
The objective of this work was to compare the release characteristics of Recombinant human bone morphogenetic protein-2 (rhBMP-2) encapsulated in thermally self-assembled poly(lactide ethylene oxide fumarate) (PLEOF) nanoparticles (NPs) with rhBMP-2 grafted to succinimide-terminated poly(lactide fumarate) (PLAF-NHS) or poly(lactide-co-glycolide fumarate) (PLGF-NHS) NPs. The amphiphilic PLEOF NPs had average size of 110 +/- 50 nm. The hydrophobic PLAF-NHS and PLGF-NHS NPs had average size of 242 +/- 67 and 195 +/- 42 nm, respectively. PLEOF NPs had rhBMP-2 encapsulation efficiency ranging from 65 to 93%. Grafting efficiency of rhBMP-2 to PLAF-NHS and PLGF-NHS NPs was 97% +/- 1% and 98% +/- 1%, respectively. PLEOF NPs displayed a relatively high-release rate of rhBMP-2 in the first week, which rapidly dropped to zero after 10 days. PLEOF NPs grafted with 10 and 20 microg/mL rhBMP-2 released 67 and 80% of the protein in the active conformation after degradation. PLGF-NHS NPs displayed sustained release of rhBMP-2 in the first 2 weeks but dropped to almost zero rate (< 3 ng/day) after 20 days. PLAF-NHS NPs showed the longest period of sustained release of active rhBMP-2 at two rates: a high rate of 25-35 ng/mL in the first 2 weeks followed by a low rate of 5-10 ng/mL from 2 to 6 weeks. Nearly, 25 and 50% of the rhBMP-2 released from PLGF-NHS and PLAF-NHS NPs, respectively, were enzymatically active after degradation of the NPs. PLEOF NPs provided a fast release of rhBMP-2 for 1 week, whereas PLAF-NHS NPs provided a slow release for up to 6 weeks.
Biomimetic Materials and Tissue Engineering Laboratories, Department of Chemical Engineering, University of South Carolina, Columbia, South Carolina 29208, USA.
Angel E
AE
Mercado
Esmaiel
E
Jabbari
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D006801:Humans; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000737:chemistry*
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D011091:Polyesters; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C512585:poly(L-lactide-co-ethylene oxide-co-fumarate); C499469:recombinant human bone morphogenetic protein-2; D011092:Polyethylene Glycols