Agnieszka Kowalczuk

Poly[tri(ethylene glycol) ethyl ether methacrylate]-coated surfaces for controlled fibroblasts culturing.

Well-defined thermosensitive poly[tri(ethylene glycol) monoethyl ether methacrylate] (P(TEGMA-EE)) brushes were synthesized on a solid substrate by the surface-initiated atom transfer radical polymerization of TEGMA-EE. The polymerization reaction was initiated by 2-bromo-2-methylpropionate groups immobilized on the surface of the wafers. The changes in the surface composition, morphology, philicity, and thickness that occurred at each step of wafer functionalization confirmed that all surface modification procedures were successful. Both the successful modification of the surface and bonding of the P(TEGMA-EE) layer were confirmed by X-ray photoelectron spectroscopy (XPS) measurements. The thickness of the obtained P(TEGMA-EE) layers increased with increasing polymerization time. The increase of environmental temperature above the cloud point temperature of P(TEGMA-EE) caused the changes of surface philicity. A simultaneous decrease in the polymer layer thickness confirmed the thermosensitive properties of these P(TEGMA-EE) layers. The thermosensitive polymer surfaces obtained were evaluated for the growth and harvesting of human fibroblasts (basic skin cells). At 37 °C, seeded cells adhered to and spread well onto the P(TEGMA-EE)-coated surfaces. A confluent cell sheet was formed within 24 h of cell culture. Lowering the temperature to an optimal value of 17.5 °C (below the cloud point temperature of the polymer, TCP, in cell culture medium) led to the separation of the fibroblast sheet from the polymer layer. These promising results indicate that the surfaces produced may successfully be used as substrate for engineering of skin tissue, especially for delivering cell sheets in the treatment of burns and slow-healing wounds.

Reversibly PEGylated nanocarrier for cisplatin delivery.

A star-shaped copolymer bearing a shell of poly(ethylene glycol) (PEG) chains was designed as a carrier of cisplatin. The proposed strategy was based on synthesis of a PEGylating agent and the incorporation of cisplatin as a reversible linker for PEG modification of the star macromolecules. The attachment of PEG chains to the stars and their release under physiological conditions, as well as the changes in particle size and mobility upon drug loading, was evidenced by diffusion ordered NMR spectroscopy (DOSY). The results demonstrated that PEGylation reduced inter-stars cross-linking and increased the stability of the nanocolloidal solution. The formation of PEG shell resulted in higher drug payload and improved drug release profile of the nanoconjugates. The in vitro bioassay in a panel of human tumor cell lines confirmed that the PEGylated conjugates exhibited superior growth inhibitory activity compared to the cisplatin-loaded nonPEGylated carrier.

Controlling the Crystallinity of Thermoresponsive Poly(2-oxazoline)-Based Nanolayers to Cell Adhesion and Detachment

Semicrystalline, thermoresponsive poly(2-isopropyl-2-oxazoline) (PIPOx) layers covalently bonded to glass or silica wafers were obtained via the surface-termination of the living polymer chains. Polymer solutions in acetonitrile were exposed to 50 °C for various time periods and were poured onto the functionalized solid wafers. Fibrillar crystallites formed in polymerization solutions settled down onto the wafers next to the amorphous polymer. The amount of crystallites adsorbed on thermoresponsive polymer layers depended on the annealing time of the PIPOx solution. The wettability of PIPOx layers decreased with the increasing amount of crystallites. The higher content of crystallites weakened the temperature response of the layer, as evidenced by the philicity and thickness measurements. Semicrystalline thermoresponsive PIPOx layers were used as biomaterials for human dermal fibroblasts (HDFs) culture and detachment. The presence of crystallites on the PIPOx layers promoted the proliferation of HDFs. Changes in the physicochemical properties of the layer, caused by the temperature response of the polymer, led to the change in the cells shape from a spindle-like to an ellipsoidal shape, which resulted in their detachment. A supporting membrane was used to assist the detachment of the cells from PIPOx biosurfaces and to prevent the rolling of the sheet.

Characterisation of different nanoparticles with a potential use for drug delivery in neuropsychiatric disorders

Abstract Objectives. Nanoparticles are promising tools for targeted delivery of drugs in the treatment of different diseases, including neuropsychiatric disorders. However, they need to be carefully characterised for any adverse effects which may occur in their presence. In this study, we evaluated the applicability of nanoparticles that belong to three different groups: (i) aggregates from amphiphilic diblock copolymers composed of poly(2-ethyl-2-oxazoline) (PEtOx) and poly(2-phenyl-2-oxazoline) (PPhOx) in different ratios, (ii) stabilised polymeric micelles (SPM) based on poly(ethylene oxide)-b-poly(propylene oxide)-bpoly(ethylene oxide) (PEO-PPO-PEO) and (iii) star-like polymer with poly(acrylic acid) arms and branched polystyrene interior (PSPAA). Methods. Using cultured human neural progenitor cells, we characterised six nanoparticles (POx-9, POx-23 and POx-46 – the polyoxazoline group, SPM-F38 and SPMMS – the SPM group, and PSPAA – the star-like polymer) for neurotoxicity and effect on neurodevelopmental genes. Nanoparticles ability to activate complement system in blood was assessed by ELISA. Results. None of the nanoparticles exhibited neurotoxicity. However, POx-9, POx-23, POx-46 and SPM-F38 activated complement system. POx-9 and SPM-F38 resulted in inhibition of expression of 19 and 26 out of 30 tested neurodevelopmental genes, respectively. Conclusions. Considering the properties of the studied nanoparticles, only PSPAA and SPMMS can be used at high concentrations for drug delivery without compromising neurogenesis and neurodevelopment, and activation of complement system.

Photocrosslinking Of Polyglycidol And Its Derivative –Route To Thermoresponsive Hydrogels

Hydrogels of biologically well‐tolerated, high‐molar‐mass polyglycidol (PGl) and its thermoresponsive derivative poly(glycidol‐co‐ethyl glycidyl carbamate) have been obtained by direct UV crosslinking in the solid state. Polymers with molar masses up to 1.45 × 106 g mol−1 were crosslinked in the presence of benzophenone or (4‐benzoylbenzyl)trimethylammonium chloride as photosensitizers. The photosensitizer concentration was varied from 2 to 10 wt%. The influence of polymer composition and photosensitizer type and amount on the crosslinking efficiency, swelling and temperature behavior of the obtained hydrogels was investigated. The photocrosslinking of PGl and poly(glycidol‐co‐ethyl glycidyl carbamate) led to hydrogels with swelling degrees up to 1700%. The swelling degrees of the hydrogels decreased with the increase of the environmental temperature indicating the thermoresponsive nature of gels. The swelling of obtained gels can be controlled by varying the composition of the copolymer precursor and by the network density.