Hanneke M. L. Lambermont-Thijs

A schizophrenic gradient copolymer: switching and reversing poly(2-oxazoline) micelles based on UCST and subtle solvent changes

The self-assembly of hydrophobic gradient copolymers of 2-nonyl-2-oxazoline and 2-phenyl-2-oxazoline in ethanol-water solvent mixtures is demonstrated to result in structures that respond to changes in temperature as well as subtle changes in the solvent composition leading to both switching and reversing of the formed micelles.

Thermoresponsive Poly(2‐oxazine)s

The monomers 2-methyl-2-oxazine (MeOZI), 2-ethyl-2-oxazine (EtOZI), and 2-n-propyl-2-oxazine (nPropOZI) were synthesized and polymerized via the living cationic ring-opening polymerization (CROP) under microwave-assisted conditions. pEtOZI and pnPropOZI were found to be thermoresponsive, exhibiting LCST behavior in water and their cloud point temperatures (T(CP)) are lower than for poly(2-oxazoline)s with similar side chains. However, comparison of poly(2-oxazine) and poly(2-oxazoline)s isomers reveals that poly(2-oxazine)s are more water soluble, indicating that the side chain has a stronger impact on polymer solubility than the main chain. In conclusion, variations of both the side chains and the main chains of the poly(cyclic imino ether)s resulted in a series of distinct homopolymers with tunable T(CP).

Linear poly(alkyl ethylene imine) with varying side chain length: synthesis and physical properties

The synthesis of a series of poly(alkyl ethylene imine) (PalkylEI) with varying side chain lengths of 1, 2, 3 and 10 carbon atoms as well as a benzyl side group was performed. A series of polymers was synthesized from a direct reduction reaction of the corresponding poly(2-oxazoline) while another series was prepared by (reductive) alkylation of linear poly(ethylene imine) (PEI). The thermal and solubility properties of the resulting polymers were investigated and compared to the starting poly(2-oxazoline)s in order to study the effects of removing the carbonyl from the polymer structure. 1H NMR spectroscopy revealed quantitative formation of the PalkylEI, i.e. no residual signals of the poly(2-oxazoline) or linear PEI were observed. Thermal investigations revealed that the thermal transitions, melting and glass transition temperatures, significantly decreased after decarboxylation due to an increase in chain flexibility. Furthermore, solubility measurements indicated that the PalkylEIs are more hydrophobic compared to the corresponding poly(2-oxazoline)s, whereby poly(ethyl ethylene imine) revealed pH and temperature responsive solubility behavior in water.

Rethinking the impact of the protonable amine density on cationic polymers for gene delivery: A comparative study of partially hydrolyzed poly(2-ethyl-2-oxazoline)s and linear poly(ethylene imine)s

&NA; To gain a more profound insight into the impact of the number and the density of protonable amines on the performance of polycations as non‐viral vectors, a series of linear poly(ethylene imine)s (LPEIs) with different numbers of ethylene imine (EI) units was compared to partially hydrolyzed (21 to 86%, 20 kDa) poly(2‐ethyl‐2‐oxazoline)s (PHPEtOxs) with a corresponding number of EI units but with varying densities. PHPEtOx polyplexes demonstrated lower transfection efficiencies than the corresponding LPEIs although having the same number of EI units as LPEI, exhibiting smaller or comparable polyplex diameters, similar zeta potentials, and similar or even preferred cyto‐ and hemocompatibility profiles. The lower efficiency was found to be related to a lower DNA binding capacity and less efficient protection of plasmid DNA against enzymatic degradation. The direct comparison of both types of polymers revealed that the density of charges within the polymer backbone seems to be more important than the total number of EI units. In conclusion, the reduction of the EI density to produce more biocompatible polyplexes must be critically examined, since the presence of high numbers of EI next to each other seems to have a dramatically higher impact on the transfection efficiency than on the in vitro toxicity. Graphical abstract Figure. No caption available.