Poly(2-oxazolines) with varying alkyl chain lengths (e.g., methyl, ethyl, aryl) and molar masses have been tested for cell cytotoxicity in vitro. A standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used for the estimation of cell viability. Two monomers, 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline, were found to provide polymers with non-cytotoxic properties. The dependence of cell viability on molar mass confirmed the expected trend; the viability increased with the higher molar mass of poly(2-ethyl-2-oxazoline) (PETOX), up to 15,000 g/mol. The results obtained for the polymers with aliphatic side chains were compared with the analogues that possessed an aromatic moiety. All results confirmed low cytotoxicity of the polymers prepared by cationic polymerization of 2-alkyl- and 2-aryl-2-oxazolines, which supports their utilization in biomedical applications. Fluorescence microscopy and steady-state fluorescence were used to observe pyrene-labeled polymer interactions with living cells. Polymer accumulated within the cells was found to be dependent on polymer concentration in media. The immunoefficiency of aromatic and aliphatic oxazoline polymers and copolymers was also studied. Phagocytic and metabolic activities of macrophages were used to assess the immunosuppressive effects of the selected copolymers for possible applications in drug delivery and immunobiology. Overall, the tested polymers demonstrated no significant influences on the cellular immunological parameters.
A series of star-shaped poly(2-ethyl-2-oxazoline)s was prepared by cationic polymerization. The polymerization was initiated by dipentaerythrityl hexakis(4-nitrobenzene sulfonate) and a tosylated hyperbranched polymer of glycidol. The polymerization proceeded in a controlled manner. The star structure of the products was determined by nuclear magnetic resonance. The molar mass distributions that were measured by gel permeation chromatography with multiangle laser light scattering were narrow, and the experimental values of the molar masses were close to those predicted. The very compact structure of the polymers obtained (compared with the linear counterparts) confirmed the star formation. The star poly(2-ethyl-2-oxazoline)s show a phase transition temperature in the range 62-75 • C. Comparison of this phase transition temperature with that of the linear poly(2-ethyl-2-oxazoline)s with the same molar masses indicates the influence of molar mass and topological structure of the macromolecule on temperature behavior. The prepared copolymers are spherical, which might be useful for the controlled transport and release of active compounds.
Inspired by the well‐known amphiphilic block copolymer platform known as Pluronics or poloxamers, a small library of ABA and BAB triblock copolymers comprising hydrophilic 2‐methyl‐2‐oxazoline (A) and thermoresponsive 2‐n‐propyl‐2‐oxazoline (B) is synthesized. These novel copolymers exhibit temperature‐induced self‐assembly in aqueous solution. The formation and size of aggregates depend on the polymer structure, temperature, and concentration. The BAB copolymers tend to agglomerate in water, with the cloud point temperature depending on the length of poly(2‐n‐propyl‐2‐oxazoline) chain. On the other hand, ABA copolymers form smaller aggregates with hydrodynamic radius from 25 to 150 nm. The dependence of viscosity and viscoelastic properties on the temperature is also studied. While several Pluronic block copolymers are known to form thermoreversible hydrogels in the concentration range 20–30 wt%, thermogelation is not observed for any of the investigated poly(2‐oxazoline)s at the investigated temperature range from 10 to 50 °C.
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