In this work, we sought to examine whether the presence of alkyl substituents randomly distributed within the main chain of a 2-isopropyl-2-oxazoline-based copolymer will decrease its ability to crystallize when compared to its homopolymer. At the same time, we aimed to ensure an appropriate hydrophilic/lipophilic balance in the copolymer and maintain the phase transition in the vicinity of the human body temperature. For this reason, copolymers of 2-ethyl-4-methyl-2-oxazoline and 2-isopropyl-2-oxazoline were synthesized. The thermoresponsive behavior of the copolymers in water, the influence of salt on the cloud point, the presence of hysteresis of the phase transition and the crystallization ability in a water solution under long-term heating conditions were studied by turbidimetry. The ability of the copolymers to crystallize in the solid state, and their thermal properties, were analyzed by differential scanning calorimetry and X-ray diffractometry. A cytotoxicity assay was used to estimate the viability of human fibroblasts in the presence of the obtained polymers. The results allowed us to demonstrate a nontoxic alternative to poly(2-isopropyl-2-oxazoline) (PiPrOx) with a physiological phase transition temperature (LCST) and a greatly reduced tendency to crystallize. The synthesis of 2-oxazoline polymers with such well-defined properties is important for future biomedical applications.

Poly(carboxybetaine methacrylate)s (PCBMA) belongs to a class of zwitterionic polymers that offer promising alternatives to polyethylene glycol (PEG) in biomedical applications. This review highlights how the unique zwitterionic structure of PCBMA dictates its strong antifouling behavior, low immunogenicity, and sensitivity to environmental stimuli such as pH and ionic strength. These features make PCBMA promising for designing advanced systems suited for complex biological environments. This review describes PCBMA-based materials—ranging from hydrogels, nanogels, and surface coatings to drug carriers and protein conjugates—and critically evaluates their performance in drug delivery, tissue engineering, diagnostics, and implantable devices. Comparative studies demonstrated that PCBMA consistently outperformed other zwitterionic polymers and PEG in resisting protein adsorption, maintaining bioactivity of conjugated molecules, and ensuring long circulation times in vivo. Molecular dynamics simulations provide additional information into the hydration shells and conformational behaviors of PCBMA in aqueous dispersions. These insights underscore PCBMA’s broad potential as a promising high-performance material for next generation healthcare technologies.

Poly(2-oxazoline) (POx) matrices in the form of non-woven fibrous mats and three-dimensional moulds were obtained by electrospinning and fused deposition modelling (FDM), respectively. To obtain these materials, poly(2-isopropyl-2-oxazoline) (PiPrOx) and gradient copolymers of 2-isopropyl- with 2-n-propyl-2-oxazoline (P(iPrOx-nPrOx)), with relatively low molar masses and low dispersity values, were processed. The conditions for the electrospinning of POx were optimised for both water and the organic solvent. Also, the FDM conditions for the fabrication of POx multi-layer moulds of cylindrical or cubical shape were optimised. The properties of the POx after electrospinning and extrusion from melt were determined. The molar mass of all (co)poly(2-oxazoline)s did not change after electrospinning. Also, FDM did not influence the molar masses of the (co)polymers; however, the long processing of the material caused degradation and an increase in molar mass dispersity. The thermal properties changed significantly after processing of POx what was monitored by increase in enthalpy of exo- and endothermic peaks in differential scanning calorimetry (DSC) curve. The influence of the processing conditions on the structure and properties of the final material were evaluated having in a mind their potential application as scaffolds.

Poly(2-isopropyl-2-oxazoline) (PiPrOx) is readily prone to crystallization both in solid and from solutions. This feature is detrimental for certain applications. Here, we examine whether the presence of unsubstituted ethyleneimine (EI) units, a gradient distributed within a polymer chain composed of 2-isopropyl-2-oxazoline (iPrOx) and 2-methyl-2-oxazoline (MOx) units, decreases the ability to crystallize the copolymer and affects thermal properties compared to the homopolymer of iPrOx. We assumed that the separation of stiff iPrOx units by the more flexible EI will affect the spatial arrangements of the ordered chains, slightly plasticize and, as a result, decrease their ability to crystallize. The selective hydrolysis of gradient iPrOx and 2-methyl-2-oxazoline (MOx) copolymers, carried out under mild conditions, led to iPrOx/MOx/EI copolymers. To the best of our knowledge, the selective hydrolysis of these copolymers has never been carried out before. Their thermal properties and crystallization abilities, both in a solid state and from an aqueous solution, were analyzed. Based on the analysis of polymer charge and cytotoxicity studies, the potential use of the copolymers obtained was indicated in some biological systems.

Copolymers of 2-isopropyl-2-oxazoline (iPrOx) with 2-methyl-2-oxazoline (MetOx) and 2-(3-butenyl)-2-oxazoline (ButEnOx) were synthesized via cationic ring opening polymerization (CROP). In the next step, the copolymers were modified to obtain primary and secondary amino groups in the substituents or in the main chain. Studies aimed to prove how the position of the amino groups in 2-oxazoline-derived copolymers influences their ability to condense DNA into so-called polyplexes. The post-polymerization modifications of the copolymers were done using hydrolysis and a thio-click reaction. The physicochemical characterization of the obtained copolymers and polyplexes was performed and then biological experiments followed to assess the cytotoxicity and transfection of the copolymers with secondary amino groups in the side chains. The results from differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS) have shown that the obtained copolymers did not contain a crystalline fraction, which makes it possible to apply them as nucleic acid carriers. The measurements of the sizes of the obtained polyplexes evidenced that the presence of primary amino groups in the substituent (POxN1pendant) impedes DNA binding, despite the positive zeta potential. On the other hand, the polymers with secondary amines, regardless the position (in the main chain for POxN2main or as a substituent in the case of POxN2pendant), form complexes with DNA to give nanostructures with smaller sizes than polymers with H₂NR displaying a negative zeta potential in the studied range of N/P values (from 3 to 10). The biological experiments have shown that the copolymer with a HNR₂ group in the pendant chain is nontoxic for HT-1080 cells in the range of concentrations from 5 to 100 μg mL⁻¹ and is able to transfect those cells.