ECTS2016 Poster Presentations Cancer and bone: basic, translational and clinical (37 abstracts)
1Leibniz-Institut für Polymerforschung Dresden e.V, Dresden, Germany; 2Technische Universität Dresden, Organische Chemie der Polymere, Dresden, Germany; 3Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 4Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany.
Calcium phosphate cements (CPC) are used as bone graft substitute, e.g. in the treatment of lytic bone lesions in multiple myeloma. CPC provide crucial advantages, such as osteoconductivity, biodegradability and the potential drug loading. Though, it lacks retarded drug release for short-/long-term treatment due to the free diffusion of small molecules through the micropores in the CPC.
Thus we present dendritic glycopolymers (DG) consisting of poly(ethylene imine) (PEI) decorated with oligo(glutamic acid) (PGlu) and/or maltose and maltotriose (Mal; Mal-III), respectively, as nanocarriers for the proteasome inhibitor bortezomib (BZM) in CPC. Thus, in aqueous solution the drug delivery systems exhibit a sufficiently high drug uptake of 54% for PEI-Mal and 73% for PEI-Mal-III, but only 35% for PEI-PGlu-Mal. Furthermore from DG/CPC composite a significant retarded BZM release is determinable. This has been observed with different polymer/drug ratios. In the table BZM release values at 37 °C are shown for 1 g CPC containing 50 μg BZM and 100 μg GD. PEI-PGlu-Mal provide the most suitable release profile for BZM.
The mechanical and morphological properties of the bone substitute are not influenced by the DG. The compressive strength remains at 2729 MPa for the CPC with and without different GD-concentrations. Moreover biocompatibility of the GD was tested by lactate dehydrogenase and alkaline phosphatase activity. GD do not affect proliferation and differentiation of hMSC: e.g. the cell number after 14 days of treatment with PEI-PGlu-Mal solutions retains constant between 12,000 and 10,000. Concluding the results CPCs loaded with BZM complexed by GD are promising materials for bone reconstruction in terms of short-/long-term treatment of cancer damaged bones.
Time | BZM without GD | PEI-Mal/BZM | PEI-Mal-III/BZM | PEI-PGlu-Mal/BZM |
3 h | 28.0% | 19.3% | 16.0% | 10.5% |
8 h | 47.2% | 37.5% | 30.1% | 15.2% |
24 h | 66.4% | 54.9% | 51.4% | 34.9% |
96 h | 70.4% | 61.1% | 63.3% | 54.2% |