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.
For better understanding and improving the non-covalent interactions of dendritic core-shell, we evaluated the interactions of hyperbranched poly(ethylene imine) (PEI) decorated with various oligosaccharide shells with water-soluble B vitamins, an estradiol derivative and pantoprazole. Depending on the different properties of the analyte molecules, dendritic core-shell glyco architectures showed (very) weak, moderate and strong interactions with the analyte molecules. Thus, ionic interactions are the strongest driving force for the formation of host-guest complexes. The core-shell glyco architecture is a necessary prerequisite for stable analyte/PEI complexes; the pure hyperbranched PEI did not show any sufficiently strong interactions with neutral, cationic or anionic analytes under the shear forces applied during ultrafiltration of pure aqueous solution without an adjusted pH. Thus, only robust non-covalent interactions between analytes and the dendritic polyamine scaffold of the glycopolymer structure survive this separation step and allow isolation of stable host-guest complexes in aqueous solution.
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