Development of an Aqueous Suspension of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)

Schwartz, Daniel (2005): Development of an Aqueous Suspension of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2): Entwicklung einer wässrigen Suspension des recombinanten menschlichen Knochenwachstumsproteins-2 (rhBMP-2). Dissertation, LMU München: Faculty of Chemistry and Pharmacy

Abstract

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.

• Item Type: Thesis (Dissertation, LMU Munich)
• Keywords: precipitation, protein integrity, protein stability, microparticles, rhBMP-2
• Subjects: 600 Natural sciences and mathematics; 600 Natural sciences and mathematics > 540 Chemistry and allied sciences
• Faculties: Faculty of Chemistry and Pharmacy
• Language: English
• Date Accepted: 31. May 2005
• 1. Referee: Frieß, Wolfgang
• Persistent Identifier (URN): urn:nbn:de:bvb:19-44316
• Signature of the printed copy: 0001/UMC 14959