Antibacterial Polymers Based on Poly(2-hydroxyethyl methacrylate) and Thiazolium Groups with Hydrolytically Labile Linkages Leading to Inactive and Low Cytotoxic Compounds.

Herein, we develop a well-defined antibacterial polymer based on poly(2-hydroxyethyl methacrylate) (PHEMA) and a derivative of vitamin B1, easily degradable into inactive and biocompatible compounds. Hence, thiazole moiety was attached to HEMA monomer through a carbonate pH-sensitive linkage and the resulting monomer was polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. N-alkylation reaction of the thiazole groups leads to cationic polymer with thiazolium groups. This polymer exhibits excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with an MIC value of 78 µg mL-1, whereas its degradation product, thiazolium small molecule, was found to be inactive. Hemotoxicity studies confirm the negligible cytotoxicity of the degradation product in comparison with the original antibacterial polymer. The degradation of the polymer at physiological pH was found to be progressive and slow, thus the cationic polymer is expected to maintain its antibacterial characteristics at physiological conditions for a relative long period of time before its degradation. This degradation minimizes antimicrobial pollution in the environment and side effects in the body after eradicating bacterial infection.

Porous Microstructured Surfaces with pH-Triggered Antibacterial Properties.

New antibacterial films are designed with the capability to reversibly regulate their killing and repelling functions in response to variations in environmental pH. These systems consist of porous polystyrene surfaces as the main components and a copolymer bearing pH-sensitive thiazole and triazole groups as the minor components. These pH-sensitive groups, located on the surfaces, can be partially protonated at acidic pH levels, increasing the positive charge density of the surfaces and their antibacterial activity. Similarly, their bacterial adhesion and killing efficiencies in response to changes in pH are evaluated by analyzing the bacterial viability of Staphylococcus aureus bacteria on the surfaces under acidic and neutral pH values. It is demonstrated that after only 1 h of incubation with the bacterial suspension in acidic conditions, the surfaces killed the bacteria, while at pH = 7.4, some of the adhered bacteria are removed. Furthermore, the surface topography exerts an important role by intensifying this response.

Antibacterial PLA Fibers Containing Thiazolium Groups as Wound Dressing Materials.

The development of inherent antimicrobial polymeric fibers can contribute to overcoming the increasing problem of infectious diseases and multiresistant microorganisms. Here, we propose the preparation of poly(lactic acid) (PLA) based electrospun fibers blended with poly[2-(4-methylthiazol-5-yl)ethyl methacrylate] (PMTA), which quaternized have proven broad spectrum antimicrobial activity either in solution or solid state. We have demonstrated that quaternized PLA/PMTA fiber mats have a remarkable antibacterial activity against S. aureus. As determined by scanning electron microscopy and Raman spectroscopy, quaternized PMTA segregates toward the outmost surface of PLA/PMTA fiber leaving the thiazolium group widely available onto the fiber surfaces, facilitating the bacteria killing by contact mode.

Antimicrobial Porous Surfaces Prepared by Breath Figures Approach.

Herein, efficient antimicrobial porous surfaces were prepared by breath figures approach from polymer solutions containing low content of block copolymers with high positive charge density. In brief, those block copolymers, which were used as additives, are composed of a polystyrene segment and a large antimicrobial block bearing flexible side chain with 1,3-thiazolium and 1,2,3-triazolium groups, PS54-b-PTTBM-M44, PS54-b-PTTBM-B44, having different alkyl groups, methyl or butyl, respectively. The antimicrobial block copolymers were blended with commercial polystyrene in very low proportions, from 3 to 9 wt %, and solubilized in THF. From these solutions, ordered porous films functionalized with antimicrobial cationic copolymers were fabricated, and the influence of alkylating agent and the amount of copolymer in the blend was investigated. Narrow pore size distribution was obtained for all the samples with pore diameters between 5 and 11 µm. The size of the pore decreased as the hydrophilicity of the system increased; thus, either as the content of copolymer was augmented in the blend or as the copolymers were quaternized with methyl iodide. The resulting porous polystyrene surfaces functionalized with low content of antimicrobial copolymers exhibited remarkable antibacterial efficiencies against Gram positive bacteria Staphylococcus aureus, and Candida parapsilosis fungi as microbial models.

Contact Active Antimicrobial Coatings Prepared by Polymer Blending.

Herein, contact active antimicrobial films are prepared by simply blending cationic amphiphilic block copolymers with commercial polystyrene (PS). The copolymers are prepared by combining atom transfer radical polymerization and "click chemistry." A variety of copolymers are synthesized, and composed of a PS segment and an antimicrobial block bearing flexible side chain with thiazole and triazole groups, 4-(1-(2-(4-methylthiazol-5-yl)ethyl)-1H-1,2,3-triazol-4-yl) butyl methacrylate (TTBM). The length of the TTBM block is varied as well as the alkylating agent. Different films are prepared from N,N-dimethylformamide solution, containing variable PS-b-PTTBM/PS ratio: from 0 to 100 wt%. Remarkably, the blend films, especially those with 30 and 50 wt% of copolymers, exhibit excellent antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi, even higher than films prepared exclusively from the cationic copolymers. Blends composed of 50 wt% of the copolymers present a more than 99.999% killing efficiency against the studied microorganisms. The better activity found in blends can be due to the higher roughness, which increases the surface area and consequently the contact with the microorganisms. These results demonstrate that the use of blends implies a reduction of the content of antimicrobial agent and also enhances the antimicrobial activity, providing new insights for the better designing of antimicrobial coatings.

Antimicrobial films obtained from latex particles functionalized with quaternized block copolymers.

New amphiphilic block copolymers with antimicrobial properties were obtained by atom transfer radical polymerization (ATRP) and copper catalyzed cycloaddition following two approaches, a simultaneous strategy or a two-step synthesis, which were proven to be very effective methods. These copolymers were subsequently quaternized using two alkyl chains, methyl and butyl, to amplify their antimicrobial properties and to investigate the effect of alkyl length. Antimicrobial experiments in solution were performed with three types of bacteria, two gram-positive and one gram-negative, and a fungus. Those copolymers quaternized with methyl iodide showed better selectivities on gram-positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, against red blood cells, demonstrating the importance of the quaternizing agent chosen. Once the solution studies were performed, we prepared poly(butyl methacrylate) latex particles functionalized with the antimicrobial copolymers by emulsion polymerization of butyl methacrylate using such copolymers as surfactants. The characterization by various techniques served to test their effectiveness as surfactants. Finally, films were prepared from these emulsions, and their antimicrobial activity was studied against the gram-positive bacteria. The results indicate that the antimicrobial efficiency of the films depends not only on the copolymer activity but also on other factors such as the surface segregation of the antimicrobial agent to the interface.

Preparation of amphiphilic glycopolymers with flexible long side chain and their use as stabilizer for emulsion polymerization.

A glycomonomer was synthesized from poly(ethylene glycol) methacrylate (PEGMA). The terminal hydroxyl moieties were activated with ester groups and subsequently the glucosamine was incorporated forming urethane linkages. The obtained glycomonomer was copolymerized with methyl acrylate by free radical polymerization varying the initial feed composition to produce different amphiphilic glycopolymers. The glycopolymers were then characterized and compared with the homologous glycopolymers based on 2-{[(D-glucosamin-2-N-yl)carbonyl]oxy}ethyl methacrylate. Both series of glycopolymers were used in emulsion polymerization of methyl acrylate as stabilizers without the addition of any cosurfactant. Although high conversions were not achieved with any of the employed surfactant, the glycopolymers provide good colloidal stability, spherical, monodisperse and small latex particles in comparison with the surfactant-free emulsion polymerization. The latex particles stabilized with the glycosurfactant based on PEGMA, containing a flexible spacer between the backbone and the glucosamine, lead to smooth films whereas the short side chain surfactant from 2-hydroxyethyl methacrylate (HEMA), with higher glass transition temperature, restricts the coalescence of particles and, therefore, the film formation. Moreover, the surface bioactivity of these polymer coatings was examined by analyzing their specific interaction with the lectin, Concanavalin A, Canavalia ensiformis. The specific and successful binding to the Concanavalin A was demonstrated by fluorescence microscopy for both series being more intense with increasing amount of glycounits in the glycopolymer stabilizers. Interestingly, the incorporation of a flexible spacer in the glycopolymer structures enhances the binding activity.

Amphiphilic polymers bearing gluconolactone moieties: synthesis and long side-chain crystalline behavior.

The synthesis and characterization of amphiphilic polymers bearing gluconolactone moieties has been described. In a first step, an unprotected glycomonomer 2-[({[4-(d-gluconamid-N-yl)butyl]amino}carbonyl)oxy]ethyl acrylate, HEAG, has been synthesized. Posterior, this glycomonomer has been copolymerized with methyl methacrylate at different compositions and the kinetic behavior has been also studied calculating the monomer reactivity ratios by Kelen-Tüdös extended equation. In addition, the long side-chain crystalline behavior of these carbohydrate-based copolymers with high composition of glycomonomer has been examined by using conventional and modulated differential scanning calorimetry and X-ray diffraction measurements. At the same time, the phase separation behavior of carbohydrate-based copolymers with lower HEAG content has been determined by their glass transition temperature measurements. Finally, the thermal stability of all these amphiphilic copolymers has been evaluated by thermogravimetric analysis.