Development of an Aqueous Suspension of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)
Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) is a morphogen with the ability to induce the formation of cartilage and new bone. In the product currently on the market for some special orthopaedic indications, rhBMP-2 is implanted by invasive surgery in combination with a suitable carrier which enables a sustained release and a prolonged presence of the morphogen at the site of action - prerequisites for an optimal therapeutic effect. The aim of the present work was to develop a sustained releasing “carrier-free”, injectable formulation that overcomes the necessity of invasive surgery and has the potential to expand the indications of rhBMP-2. Based on the principle of controlled precipitation, a microparticulate formulation was developed. Beside physicochemical characterisations of the microparticles, the integrity of rhBMP-2 in the precipitated state and after redissolution was demonstrated and the potential of precipitation to prevent degradation was elucidated. The ability of the microparticle formulation to deliver rhBMP-2 in a sustained manner was tested in-vitro and the efficacy of the aqueous protein suspension to augment bone density was examined in an animal model.