Dendritic Glycopolymer as Drug Delivery System for Proteasome Inhibitor Bortezomib in a Calcium Phosphate Bone Cement: First Steps Toward a Local Therapy of Osteolytic Bone Lesions.

Christin Striegler, Matthias Schumacher, Christiane Effenberg, Martin Müller, Anja Seckinger, Reinhard Schnettler, Brigitte Voit, Dirk Hose, Michael Gelinsky, Dietmar Appelhans

Journal: Macromolecular bioscience 2016;15(9):1283-95

PMID: 26018141

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Abstract

Establishment of drug delivery system (DDS) in bone substitute materials for local treatment of bone defects still requires ambitious solutions for a retarded drug release. We present two novel DDS, a weakly cationic dendritic glycopolymer and a cationic polyelectrolyte complex, composed of dendritic glycopolymer and cellulose sulfate, for the proteasome inhibitor bortezomib. Both DDS are able to induce short-term retarded release of bortezomib from calcium phosphate bone cement in comparison to a burst-release of the drug from bone cement alone. Different release parameters have been evaluated to get a first insight into the release mechanism from bone cements. In addition, biocompatibility of the calcium phosphate cement, modified with the new DDS was investigated using human mesenchymal stromal cells.

Address: Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany.; Organic Chemistry of Polymers, Technische Universität Dresden, 01062 Dresden, Germany.; Centre for Translational Bone, Joint and Soft Tissue Research, Medical Faculty and University Hospital, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.; Department of Internal Medicine V, Section Multiple Myeloma, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.; Laboratory for Experimental Trauma Surgery, Justus-Liebig-University Gießen, Schubertstr. 81, 35392 Giessen, Germany.; Department of Internal Medicine V, Section Multiple Myeloma, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. [email protected].; Centre for Translational Bone, Joint and Soft Tissue Research, Medical Faculty and University Hospital, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. [email protected].; Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany. [email protected].

DOI: 10.1002/mabi.201500085

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MeSH Terms: Bone Cements, Bortezomib, Calcium Phosphates, Cellulose, Delayed-Action Preparations, Dendrimers, Humans, Maltose, Mesenchymal Stem Cells, Osteogenesis, Polyethyleneimine, Proteasome Inhibitors