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.
We report the design of the fourth generation poly(propylene imine) (PPI) glycodendrimers for magnetic resonance (MR) imaging applications. The glycodendrimers were designed to have a densely organized maltose shell (MAL DS) and several tetraazacyclododecane tetraacetic acid (DOTA) ligands that were attached to the periphery of the PPI dendrimers for Gd(iii) chelation. We show that the formed MAL DS-modified PPI dendrimers possess good cytocompatibility and hemocompatibility in the studied concentration range. With the longitudinal relaxivity (r) of PPI-MAL DS-DOTA(Gd) (10.2 mM s), which is 3.0 times higher than that of DOTA(Gd) (3.4 mM s), the developed PPI-MAL DS-DOTA(Gd) nanocomplexes can be used as an efficient contrast agent for MR imaging of cancer cells in vitro, and animal aorta, renal artery, kidney, and bladder in vivo. Furthermore, tissue distribution studies show that the glycodendrimer/Gd complexes are metabolized and cleared out of the body at 48 h post injection. The developed PPI-MAL DS-DOTA(Gd) may be further functionalized for MR imaging of different biological systems.
The development of compartments for the design of cascade
reactions
in a local space requires a selective spatiotemporal control. The
combination of enzyme-loaded polymersomes with enzymelike units shows
a great potential in further refining the diffusion barrier and the
type of reactions in nanoreactors. Herein, pH-responsive and ferrocene-containing
block copolymers were synthesized to realize pH-stable and multiresponsive
polymersomes. Permeable membrane, peroxidase-like behavior induced
by the redox-responsive ferrocene moieties and release properties
were validated using cyclovoltammetry, dye TMB assay, and rupture
of host–guest interactions with β-cyclodextrin, respectively.
Due to the incorporation of different block copolymers, the membrane
permeability of glucose oxidase-loaded polymersomes was changed by
increasing extracellular glucose concentration and in TMB assay, allowing
for the chemoenzymatic cascade reaction. This study presents a potent
synthetic, multiresponsive nanoreactor platform with tunable (e.g.,
redox-responsive) membrane properties for potential application in
therapeutics.
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