Swelling behavior of bisensitive interpenetrating polymer networks for microfluidic applications.

Bisensitive interpenetrating polymer network (IPN) hydrogels of temperature sensitive net-poly(N-isopropylacrylamide) and pH sensitive net-poly(acrylic acid-co-acrylamide) for microfluidic applications were prepared via a sequential synthesis using free radical polymerization. The IPN indicated a suitable reversible alteration of swelling in response to the change in pH and temperature. The adequate change of the hydrogel volume is a basic requirement for microfluidic applications. Using the introduced correction factor f, it is possible to determine the cooperative diffusion coefficient (Dcoop) of cylindrical samples at any aspect ratio. The determined cooperative diffusion coefficient allowed the evaluation of varying swelling processes of different network structures. The presence of the second sub-network of the IPN improved the swelling behaviour of the first sub-network compared to the individual networks.

Potential of Ni(II)-NTA-modified poly(ethylene imine) glycopolymers as carrier system for future dendritic cell-based immunotherapy.

Dendritic cells (DCs) play a crucial role in the development of cell-mediated immunotherapy due to their ability to induce and maintain strong immune responses. In our study, we evaluated a biocompatible Ni(II)-NTA-modified poly(ethylene imine) dendritic glycopolymer (Ni(II)-NTA-DG) as new carrier system to increase the antigen uptake into iDCs for future DC-based immunotherapy. Ni(II)-NTA-DG led to an increase in His6-Gp160 uptake in monocytes and iDCs, where His6-Gp160 is localized in the early endosomal and lysosomal compartments. Ni(II)-NTA-DG and the formed polyplexes induced an activation of iDCs, showing an increasing expression of costimulatory molecules CD86, CD80, and proinflammatory cytokines IL-6 and IL-8. Beside no influencing effect of Ni(II)-NTA-DG and polyplexes on the maturation of antigen-bearing DCs, the mature peptide bearing DCs remained their ability to migrate along a gradient of CCR7 ligands. Thus, Ni(II)-NTA-DG with advancing biological properties is a promising carrier system for the future application in DC-based immunotherapy.

Studying complexes between PPI dendrimers and Mant-ATP.

The aim of this study was to investigate the interactions between poly(propylene imine) (PPI) dendrimers and 2'-/3'-O-(N'-methylanthraniloyl)-ATP (Mant-ATP). Mant-ATP was used as a model molecule. Purine and pyrimidine nucleoside analogues are antimetabolites commonly used in therapy for cancer. Drug molecules can complex with dendrimers in two ways: therapeutic agents may be attached in dendrimer interior or bind to functional groups on the surface. Drugs attached to nanoparticles are characterized by improved solubility, pharmacokinetics and stability. Here, we have used poly(propylene imine) dendrimers of the 4th and 5th generations (PPI G4 and PPI G5) with primary amino surface groups partially modified with maltose (PPI-m) or without modification (PPI). We assessed the efficiency of complex formation in relation to dendrimer generation, pH of solution and the type of dendrimer used. A double fluorimetric titration method was used to estimate the binding constant (K b ) and the number of binding centers per molecule of the binding agent (n).

pH-triggered aggregate shape of different generations lysine-dendronized maleimide copolymers with maltose shell.

Glycopolymers are promising materials in the field of biomedical applications and in the fabrication of supramolecular structures with specific functions. For tunable design of supramolecular structures, glycopolymer architectures with specific properties (e.g., controlled self-assembly) are needed. Using the concept of dendronized polymers, a series of H-bond active giant glycomacromolecules with maleimide backbone and lysine dendrons of different generations were synthesized. They possess different macromolecular size and functionality along the backbone. Their peripheral maltose units lead to solubility under physiological conditions and controlled aggregation behavior. The aggregation behavior was investigated depending on generation number, pH value, and concentration. A portfolio of complementary analytical tools give an insight into the influence of the different parameters in shaping a rod-, coil-, and worm-like molecular structure and their controlled aggregate formation. MD simulation helped us to understand the complex aggregation behavior of the linear polymer chain without dendritic units.

Soft and flexible poly(ethylene glycol) nanotubes for local drug delivery.

Nanotubes are emerging as promising materials for healthcare applications but the selection of clinically relevant starting materials for their synthesis remains largely unexplored. Here we present, for the first time, the synthesis of poly(ethylene glycol) (PEG) based nanotubes via the photopolymerization of poly(ethylene glycol) diacrylate and other diacrylate derivatives within the pores of anodized aluminum oxide templates. Template-assisted synthesis allowed the manufacture of a diverse set of polymeric nanotubes with tunable physical characteristics including diameter (∼200-400 nm) and stiffness (405-902 kPa). PEG nanotubes were subjected to cytotoxicty assessment in cell lines and primary stem cells and showed excellent cytocompatability (IC50 > 120 µg ml-1). Nanotubes were readily drug loaded but released the majority of the drug over 5 days. Direct administration of drug loaded nanotubes to human orthotopic breast tumors substantially reduced tumor growth and metastasis and outperformed i.v. administration at the equivalent dose. Overall, this nanotube templating platform is emerging as a facile route for the manufacture of poly(ethylene glycol) nanotubes.

Hexacyano-[3]-radialene anion-radical salts: a promising family of highly soluble p-dopants.

Organic and inorganic salts of the hexacyano-[3]-radialene anion-radical are readily available and thermally stable compounds (up to ∼180 °C). The tetrabutylammonium salt exhibits an extremely high solubility in a range of solvents (>300 mg l-1 in CHCl3) and acts as an efficient p-dopant for poly(3-hexylthiophene) to provide composite films with a conductivity above 2 S cm-1.

In vitro blood compatibility of polymeric biomaterials through covalent immobilization of an amidine derivative.

We present a surface coating with anticoagulant characteristics showing significantly reduced coagulation activation. The synthesis of a monomeric conjugate containing a benzamidine moiety was carried out and its inhibitory activity against human thrombin, the key enzyme of the blood coagulation cascade, was determined using a chromogenic assay. Based on that, low-thrombogenic interfaces were prepared by covalent attachment of this low-molecular weight thrombin inhibitor on poly(octadecene-alt-maleic anhydride) copolymer thin films and characterized using ellipsometry, XPS and dynamic contact angle measurements. The in vitro hemocompatibility tests using freshly drawn human whole blood showed, in agreement with the SEM images, that a PO-MA film modified with a benzamidine moiety using a PEG spacer decreased the activation of coagulation, platelets and the complement system. The decreased protein adsorption, in addition to the specific inhibition of thrombin, effectively enhanced the short-term hemocompatibility characteristics.

Internalization and intracellular trafficking of poly(propylene imine) glycodendrimers with maltose shell in melanoma cells.

The diagnosis and treatment of malignant melanoma by means of the formulation of active principles with dendrimeric nanoparticles is an area of great current interest. The identification and understanding of molecular mechanisms which ensure the integration of particular dendrimeric nanostructures in tumor cellular environment can provide valuable guidance in their coupling strategies with antitumor or diagnostic agents. Two structurally distinct maltose-shell modified 5th generation (G5) poly(propylene imine) (PPI) glycodendrimers fluorescently labeled, (a) with open maltose shell, cationic charged G5-PPI-OS and (b) with dense maltose shell and nearly neutral G5-PPI-DS, were tested in relation with several melanoma cell lines. We found that three melanoma cell lines internalize G5-PPI-DS structure more efficiently than non tumoral HEK297T cells. Furthermore, the internalization pathways of G5-PPI-OS and G5-PPI-DS are characteristic for each tumor cell phenotype and include more than one mechanism. As a general trend, large amounts of both G5-PPI-OS and G5-PPI-DS are internalized on cholesterol-dependent pathway in MJS primary melanoma cells and on non conventional pathways in SK28 metastatic melanoma cells. G5-PPI-OS, temporarily retained at plasma membrane in both cell lines, is internalized slower in metastatic than in primary phenotype. Unlike G5-PPI-OS, G5-PPI-DS is immediately endocytosed in both cell lines. The unconventional internalization pathway and trafficking, exclusively used by G5-PPI-DS in metastatic cells, is described at molecular level. The decay kinetics of fluorescent labeled G5-PPI-OS and G5-PPI-DS is distinct in the two cellular phenotypes. Both cationic and neutral maltose G5-PPI glycodendrimeric structures represent molecules based on which designing of new formulations for therapy or/and diagnosis of melanoma can be further developed.

Photolabile carboxylic acid protected terpolymers for surface patterning. Part 1: Polymer synthesis and film characterization.

We present the synthesis and characterization of a series of photolabile phenacyl derivative polymers and their subsequent thin film preparation. These systems are composed of up to three methacrylate units: a photolabile component including a p-methoxyphenacyl moiety which after selective irradiation (UV/laser) can provide free carboxylic groups in specific areas for further modification; an anchoring unit, trimethoxysiloxane or glycidyl methacrylate derivative, which allows the covalent attachment of the polymer to the substrate; and a spacer, methyl methacrylate or styrene, which in the appropriate proportion ensures the formation of films with good quality. Structural and thermal properties of these materials have been analyzed by means of NMR, FTIR, elemental analysis, UV, gel permeation chromatography, differental scanning calorimetry, and thermogravimetric analysis. The polymers have been subsequently processed by spin coating to render ultrathin films (<50 nm). Topographic and structural characterization studies of the films have been carried out with atomic force microscopy, contact angle measurements, and X-ray photoelectron spectroscopy. The extent of the substrate attachment of the polymers depending on the nature of the anchoring groups have been studied by ellipsometry and FTIR.

Photolabile carboxylic acid protected terpolymers for surface patterning. Part 2: Photocleavage and film patterning.

The surface properties of films made of p-methoxyphenacyl derivative terpolymers, associated with photocleavage by UV irradiation, and their optical patterning are investigated. The deprotection reaction has been monitored by UV and FTIR spectroscopy, contact angle measurements, and X-ray photoelectron spectroscopy, revealing the photoremoval of the protecting p-methoxyphenacyl group in high yields under mild conditions. Parallel and serial patterning of the films has been performed by selective irradiation through optical masks and by laser irradiation via fiber tips of a scanning near-field optical microscope, respectively. By irradiation of photolabile protected functional groups, free carboxylic groups become exposed to the surface with which fluorescent dyes and proteins can be associated specifically.

Molecular dynamics of hyperbranched polyesters in the confinement of thin films.

Broadband Dielectric Spectroscopy is employed to investigate the molecular dynamics in thin films of hyperbranched polyesters (type AB(1)B(2), with -OH and -OCOCH(3) as terminal groups). Three relaxation processes are detected: alpha, beta and gamma. While the latter two are not influenced by the confinement, a pronounced effect is observed on the alpha relaxation: with decreasing film thickness the slower relaxation modes of the dynamic glass transition are gradually suppressed, resulting in an increase of the average relaxation rate and in a linear decrease of the dielectric strength. This is attributed to an immobilization in confinement of the polymeric segments located at the periphery of the hyperbranched macromolecular structures.