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.