Effect of molecular weight of thermoreversible polymer on in vivo retention of rhBMP-2

To investigate the effect of polymer molecular weight (MW) on rhBMP-2 deliv ery by thermoreversible polymers, four polymers with similar lower critical solution temperatures (20 degrees -22 degreesC) but different MWs were stu died. Thermoreversible polymers were based on N-isopropyl-acrylamide (NiPAM ), ethyl methacrylate (EMA), and N-acryloxvsuccinimide (NASI), and had MWs of either similar to 49 kDa or similar to 400 kDa. The NASI content was eit her 0 or 1-1.6%. High MW polymers, irrespective of their NASI content, form ed a stable gel with significantly lower water uptake and exhibited a dense micelle with average pore size smaller than the low MW polymers. NiPAM/EMA polymers without NASI did not conjugate with recombinant human bone morpho genetic protein-2 (rhBMP-2). NiPAM/EMA polymers containing NASI, however, g ave conjugation with rh-BMP-2. For polymers without NASI, a high MW was ess ential for rhBMP-2 retention when injected intramuscularly in Sprague-Dawle y rats. For NASI-containing polymers, the MW of the polymer did not make a significant difference because rhBMP-2 retention was equivalent for differe nt size polymers. We conclude that polymer MW affects rhBMP-2 retention in vivo in polymers designed for physical entrapment of rhBMP-2, but not in po lymers designed for chemical conjugation with rhBMP-2. (C) 2001 John Wiley & Sons, Inc.