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Biofilm formation is considered one of the primary virulence mechanisms in Gram-positive and Gram-negative pathogenic species, particularly those responsible for chronic infections and promoting bacterial survival within the host. In recent years, there has been a growing interest in discovering new compounds capable of inhibiting biofilm formation. This is considered a promising antivirulence strategy that could potentially overcome antibiotic resistance issues. Effective antibiofilm agents should possess distinctive properties. They should be structurally unique, enable easy entry into cells, influence quorum sensing signaling, and synergize with other antibacterial agents. Many of these properties are found in both natural systems that are isolated from plants and in synthetic systems like nanoparticles and nanocomposites. In this review, we discuss the clinical nature of biofilm-associated infections and some of the mechanisms associated with their antibiotic tolerance. We focus on the advantages and efficacy of various natural and synthetic compounds as a new therapeutic approach to control bacterial biofilms and address multidrug resistance in bacteria.

In this work, mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA 29 -b-PCL 70 -b-PDMAEMA 29 ) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO 99 -b-PPO 67 -b-PEO 99 ) triblock copolymers, blended at different molar ratios, were developed. The key physicochemical parameters of MPMs, including size, size distribution, and critical micellar concentration (CMC), were evaluated. The resulting MPMs are nanoscopic with a hydrodynamic diameter of around 35 nm, and the ζ-potential and CMC values strongly depend on the MPM's composition. Ciprofloxacin (CF) was solubilized by the micelles via hydrophobic interaction with the micellar core and electrostatic interaction between the polycationic blocks, and the drug localized it, to some extent, in the micellar corona. The effect of a polymer-to-drug mass ratio on the drug-loading content (DLC) and encapsulation efficiency (EE) of MPMs was assessed. MPMs prepared at a polymer-to-drug mass ratio of 10:1 exhibited very high EE and a prolonged release profile. All micellar systems demonstrated their capability to detach pre-formed Gram-positive and Gram-negative bacterial biofilms and significantly reduced their biomass. The metabolic activity of the biofilm was strongly suppressed by the CF-loaded MPMs indicating the successful drug delivery and release. The cytotoxicity of empty and CF-loaded MPMs was evaluated. The test reveals composition-dependent cell viability without cell destruction or morphological signs of cell death.

The interactions of two star polymers based on poly (2-(dimethylamino)ethyl methacrylate) with different types of nucleic acids are investigated. The star polymers differ only in their functionality to bear protonable amino or permanently charged quaternary ammonium groups, while DNAs of different molar masses, lengths and topologies are used. The main physicochemical parameters of the resulting polyplexes are determined. The influence of the polymer' functionality and length and topology of the DNA on the structure and properties of the polyelectrolyte complexes is established. The quaternized polymer is characterized by a high binding affinity to DNA and formed strongly positively charged, compact and tight polyplexes. The parent, non-quaternized polymer exhibits an enhanced buffering capacity and weakened polymer/DNA interactions, particularly upon the addition of NaCl, resulting in the formation of less compact and tight polyplexes. The cytotoxic evaluation of the systems indicates that they are sparing with respect to the cell lines studied including osteosarcoma, osteoblast and human adipose-derived mesenchymal stem cells and exhibit good biocompatibility. Transfection experiments reveal that the non-quaternized polymer is effective at transferring DNA into cells, which is attributed to its high buffering capacity, facilitating the endo-lysosomal escape of the polyplex, the loose structure of the latter one and weakened polymer/DNA interactions, benefitting the DNA release.

Poly(2-oxazoline)s (POx) are an attractive platform for the development of non-viral gene delivery systems. The combination of POx moieties, exhibiting excellent biocompatibility, with DNA-binding polyethyleneimine (PEI) moieties into a single copolymer chain is a promising approach to balance toxicity and transfection efficiency. The versatility of POx in terms of type of substituent, copolymer composition, degree of polymerization, degree of hydrolysis, and chain architecture, as well as the introduction of stimuli-responsive properties, provides opportunities to finely tune the copolymer characteristics and physicochemical properties of the polyplexes to increase the biological performance. An overview of the current state of research in the POx-PEI-based gene delivery systems focusing particularly on thermosensitive POx is presented in this paper.

Contamination of surfaces in hospitals and food industry by bacterial biofilms is a serious health risk. Of concern is their resistance to routine antibacterials and disinfectants. This requires the development of novel approaches to biofilm detachment. The study evaluates the effectiveness of cationic polymer micelles (CPMs) against pre-formed biofilms. CPMs based on different polycations were used. The hydrodynamic radius of the particles ranged from 16 to 360 nm. Biofilms of Escherichia coli 420, Pseudomonas aeruginosa PAO1, Staphylococcus aureus 29213 and Bacillus subtilis 168 were cultivated for 24 h then the pre-formed biofilms were treated with the CPMs for 2, 4 or 6 h. Biofilm biomass was evaluated by the crystal violet assay, and live/dead fluorescence test was applied for bacterial viability. The ability of CPMs to interact with pre-formed biofilms of the model strains was evaluated. We observed that the most effective CPMs were those based on poly(2-(dimethylamino)ethyl methacrylate) copolymers which reduced the biofilm biomass three- to four-fold compared with the treatment of the biofilm with water. Significantly reduced vitality of the bacteria in the biofilms was registered by the live/dead stain. The results indicate the applicability of the CPMs for disinfection of biofilm-contaminated surfaces and the treatment of wounds., (© 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work we focus on the use of novel homo and block copolymers based on poly(vinyl benzyl trimethylammonium chloride) as gene delivery vectors. The homopolymers and block copolymers were synthesized by RAFT polymerization schemes and molecularly characterized. DNA/polymer complexes (polyplexes) in a wide range of N/P (amino-to-phosphate groups) ratios were prepared. The ability of the novel polymers to form complexes with linear DNA was investigated by light scattering, zeta potential, and ethidium bromide fluorescence quenching measurements. The resulting polyplexes were in the size range of 80-300 nm and their surface potential changed from negative to positive depending on the N/P ratio. The stability of polyplexes was monitored by changes in their hydrodynamic parameters in the presence of salt. The novel vector systems were visualized by transmission electron microscopy. The influence of factors such as molar mass, content, and chemical structure of the polycationic moieties as well as presence of a hydrophilic poly[oligo(ethylene glycol) methacrylate] block on the structure and stability of the polyplexes, kinetics of their formation, and effectiveness of the (co)polymers to shrink and pack DNA was discussed.