Stretched or wrinkled? Looking into the polymer conformation within polymersome membranes.

Self-assembly of amphiphilic block-copolymers into polymersomes is a well-established concept. In this membrane, the hydrophilic part is considered to be loosely assembled towards the solvent, and the hydrophobic part on the inside of the membrane is considered to be more densely packed. Within the membrane, this hydrophobic part could now have a stretched conformation or be a random coil, depending on the available space and also on the chemical nature of the polymer. We now analysed the literature for works on polymersomes that determined the membrane thickness via cryo-TEM and analysed the hydrophobic part of their polymers for their conformation. Over all available block-copolymers, a variety of trends became obvious: the longer a hydrophobic block, the more coiled the conformation and the bulkier the side chains, the more stretched the polymer became. Polymers with less conformational freedom like semi-crystalline ones were present in a more stretched conformation. Both trends could be exemplified on various occasions in this cross-literature meta-study. This overview hence provides additional insight into the physical chemistry of block-copolymer membranes.

Redox- and pH-Responsive Polymersomes with Ferrocene Moieties Exhibiting Peroxidase-like, Chemoenzymatic Activity and H2O2-Responsive Release Behavior.

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 ß-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.

Poly(propylene imine) dendrimers with histidine-maltose shell as novel type of nanoparticles for synapse and memory protection.

Poly(propylene imine) dendrimers have been shown to be promising 3-dimensional polymers for the use in the pharmaceutical and biomedical applications. Our aims of this study were first, to synthesize a novel type of dendrimer with poly(propylene imine) core and maltose-histidine shell (G4HisMal) assessing if maltose-histidine shell can improve the biocompatibility and the ability to cross the blood-brain barrier, and second, to investigate the potential of G4HisMal to protect Alzheimer disease transgenic mice from memory impairment. Our data demonstrate that G4HisMal has significantly improved biocompatibility and ability to cross the blood-brain barrier in vivo. Therefore, we suggest that a maltose-histidine shell can be used to improve biocompatibility and ability to cross the blood-brain barrier of dendrimers. Moreover, G4HisMal demonstrated properties for synapse and memory protection when administered to Alzheimer disease transgenic mice. Therefore, G4HisMal can be considered as a promising drug candidate to prevent Alzheimer disease via synapse protection.

Sweet Polymers: Poly(2-ethyl-2-oxazoline) Glycopolymers by Reductive Amination.

Carbohydrates are important in signaling, energy storage, and metabolism. Depending on their function, carbohydrates can be part of larger structures, such as glycoproteins, glycolipids, or other functionalities (glycoside). To this end, polymers can act as carriers of carbohydrates in so-called glycopolymers, which mimic the multivalent carbohydrate functionalities. We chose a biocompatible poly(2-ethyl-2-oxazoline) (PEtOx) as the basis for making glycopolymers. Via the partial hydrolysis of PEtOx, a copolymer of PEtOx and polyethylenimine (PEI) was obtained; the subsequent reductive amination with the linear forms of glucose and maltose yielded the glycopolymers. The ratios of PEtOx and carbohydrates were varied systematically, and the solution behaviors of the resulting glycoconjugates are discussed. Dynamic light scattering (DLS) revealed that, depending on the carbohydrate ratio, the glycopolymers were either fully water-soluble or formed agglomerates in a temperature-dependent manner. Finally, these polymers were tested for their biological availability by studying their lectin binding ability with Concanavalin A.

Gd-Chelated poly(propylene imine) dendrimers with densely organized maltose shells for enhanced MR imaging applications.

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 (r1) of PPI-MAL DS-DOTA(Gd) (10.2 mM-1 s-1), which is 3.0 times higher than that of DOTA(Gd) (3.4 mM-1 s-1), 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.

Characterization of oligosaccharide-functionalized hyperbranched poly(ethylene imine) and their complexes with retinol in aqueous solution.

Structure, internal density distribution, and size of hyperbranched poly(ethylene imine) (PEI) functionalized with various amounts of maltose (PEI-Mal) in phosphate buffer were studied by small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). The value of pH was varied in the range from 3 to 9. Virtually no effect of pH on the nanostructure was found in this interval. The SAXS results revealed a broad segmental radial density distribution, i.e. a "fluffy" globular structure rather than a distinct core-shell structure with a high-density compact core and a low-density corona. This suggests that the maltose units are rather evenly distributed both in the interior and on the surface of the species with a PEI-core of molar mass of 25,000g/mol. The DLS measurements showed that the overall size of the PEI-Mal derivatives increased as the number of maltose units in the PEI-Mal structures rises. The interaction of the hydrophobic model drug retinol with PEI or PEI-Mal derivatives was also investigated. The UV-visible spectroscopy results disclosed that the solubility of retinol in the phosphate buffer is very poor and it takes a very long time to solubilize retinol. Moreover, retinol induces aggregation of dendritic glycopolymers where the growth of aggregates occurs continuously over several days and then remains virtually constant.

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.

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.