Reversible addition–fragmentation chain transfer (RAFT) copolymerization was used to prepare copolymers of N-isopropyl acrylamide (NIPAM) and vinyl acetate (VAc) with mole fractions of NIPAM ranging from 0.1 to 0.6 and targeted degrees of polymerization of 100 and 250. The measured kinetic parameters and obtained experimental results revealed that this copolymerization system leads to a “one pot” synthesis of amphiphilic gradient copolymers, which have thermoresponsive and self-assembly characteristics resembling those of the analogous block copolymers but with some intriguing differences. Their self-assembly behavior in water suggests the formation of dynamic aggregates which respond rapidly to changes in solubility as revealed by ¹H NMR spectroscopy, in contrast to the kinetically frozen aggregates formed by block copolymers. Furthermore, despite their block-like composition profiles, these copolymers display a single and broad glass transition, as is typically found in linear gradient copolymers. The synthetic approach presented in this contribution could readily be adapted to other comonomer systems to provide an accessible and economic alternative to the conventional multi-step preparation of block copolymers.

The rise of antibiotic-resistant microorganisms has become a critical issue in recent years and has promoted substantial research efforts directed to the development of more effective antimicrobial therapies utilizing different bactericidal mechanisms to neutralize infectious diseases. Modern approaches employ at least two mixed bioactive agents to enhance bactericidal effects. However, the combinations of drugs may not always show a synergistic effect, and further, could also produce adverse effects or stimulate negative outcomes. Therefore, investigations providing insights into the effective utilization of combinations of biocidal agents are of great interest. Sometimes, combination therapy is needed to avoid resistance development in difficult-to-treat infections or biofilm-associated infections treated with common biocides. Thus, this contribution reviews the literature reports discussing the usage of antimicrobial polymers along with nanomaterials or other inhibitors for the development of more potent biocidal therapies.

A series of dual pH- and ultrasound responsive statistical copolymers were synthesized via the reversible addition–fragmentation chain transfer (RAFT) polymerization of 3,4-dihydro-2H-pyran (DHP) protected HEMA 2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl methacrylate (THP-HEMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The RAFT-controlled nature of the (co)polymerizations was verified by detailed kinetic studies. The chemical structure and the co-monomer composition of the copolymers were confirmed by ¹H NMR spectroscopy. The number-average molar mass values (M_n) and dispersities (Đ_M = M_w/M_n) of the copolymers were estimated by size exclusion chromatography (SEC). The thermal properties of the (co)polymers were analyzed by means of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Additionally, the DMAEMA moieties of the copolymers were quaternized with an excess of methyl iodide. The synthesized polymers self-assemble into nanoparticles in aqueous media via the nanoprecipitation method and were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Zeta potential measurements revealed that all DMAEMA containing nanoparticles undergo a surface charge conversion from positive to negative at slightly acidic pH values. However, quaternized DMAEMA nanoparticles possess pH independent positive surface charges. At acidic pH values, the nanoparticles disassemble and dissolve in water due to the protonation of the DMAEMA moieties and/or due to the acidic hydrolysis of the THP-HEMA groups. It was found that the surface charge and the stability of the nanoparticles were greatly affected by the DMAEMA content of the polymers, meaning that the isoelectric point (IEP), at which the charge is reversed and the pH value at which the disassembly occurs, increased with the higher DMAEMA content in the copolymer. Moreover, it was proven that the ionization of the carboxyl RAFT end-group of the polymers enhanced the anionic character and the stability of the nanoparticles at neutral pH values. DLS and scanning electron microscopy (SEM) measurements revealed that these nanoparticles can be further disrupted by ultrasound exposure. Nile Red was encapsulated into nanoparticles as a model hydrophobic drug. The release profile of the Nile Red was significantly accelerated in acidic media or under ultrasound exposure. The cytotoxicity assay results showed that negatively charged nanoparticles are non-toxic and biocompatible, whereas positively charged nanoparticles are extremely toxic to L929 cells.