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 μg/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. Microsc. Res. Tech. 73:824–833, 2010. © 2010 Wiley‐Liss, Inc.