L. D'Ilario

Polyurethane anionomers containing metal ions with antimicrobial properties: Thermal, mechanical and biological characterization

In recent years the employment of implantable medical devices has increased remarkably, notwithstanding that microbial infections are a frequent complication associated with their use. Different strategies have been attempted to overcome this problem, including the incorporation of antimicrobial agents into the device itself. In this study a new approach to obtain intrinsically antimicrobial materials was developed. Polymer anionomers containing Ag(I), Cu(II), Zn(II), Al(III) and Fe(III) were prepared by neutralization of a carboxylated polyurethane. In the case of the PEUA-Ag, PEUA-Fe and PEUA-Cu ionomers the ion aggregates behaved as reinforcing filler particles, increasing the mechanical properties of the systems in terms of hardness and strength at break over the pristine carboxylated polymer. With the exception of the Al-containing polymer, all the other experimented ionomers showed satisfactory antimicrobial properties. The best antibacterial effect was obtained with the silver ion-containing polymer, which inhibited Staphylococcus epidermidis growth for up to 16days. Ciprofloxacin was also adsorbed onto the above mentioned ionomers. A synergistic effect of the antibiotic and silver ions on bacterial growth inhibition was observed for at least 25days.

Water Soluble Usnic Acid-Polyacrylamide Complexes with Enhanced Antimicrobial Activity against Staphylococcus epidermidis

Usnic acid, a potent antimicrobial and anticancer agent, poorly soluble in water, was complexed to novel antimicrobial polyacrylamides by establishment of strong acidic-base interactions. Thermal and spectroscopic analysis evidenced a molecular dispersion of the drug in the polymers and a complete drug/polymer miscibility for all the tested compositions. The polymer/drug complexes promptly dissolved in water and possessed a greater antimicrobial activity against Staphylococcus epidermidis than both the free drug and the polymer alone. The best results were obtained with the complex based on the lowest molecular weight polymer and containing a low drug content. Such a complex showed a larger inhibition zone of bacterial growth and a lower minimum inhibitory concentration (MIC) with respect to usnic acid alone. This improved killing effect is presumably due to the reduced size of the complexes that allows an efficient cellular uptake of the antimicrobial complexes. The killing effect extent seems to be not significantly dependent on usnic acid content in the samples.

Water state effect on drug release from an antibiotic loaded polyurethane matrix containing albumin nanoparticles.

Water mobility plays a crucial role in determining transport properties of small molecules in polymer matrices. In particular, in drug delivery systems, water state affects the pharmacokinetics, especially drug absorption, diffusion and release. In the present study, the state of water in an antibiotic-loaded composite consisting of albumin nanoparticles (BSA(np)) dispersed into a carboxylated polyurethane (PEUA) has been investigated and compared with that of the single drug-loaded components. The antibiotic cefamandole nafate was used as a model drug. DSC analysis, used to evaluate the freezing and non-freezing water fractions in the hydrated samples, showed that in BSA(np) water can adsorb both in the inter-particles regions and inside the particles. With increasing of total adsorbed water amount, the contribution of the freezing water fraction was higher than the non-freezing one. As for PEUA, the majority of water molecules absorbed is in a mobile freezing state (about 60% of the W(tot)). As for the PEUA/BSA(np) composite, the higher polyurethane phase segregation induced by the nanoparticles as well as the higher non-freezing water fraction significantly enhanced drug uptake with respect to PEUA. Moreover, the greater non-freezing water fraction allowed the drug to penetrate within BSA nanoparticles and to give rise then to a controlled drug release. Indeed, the diffusion barrier exerted by nanoparticles and the matrix prolonged the antimicrobial activity from 4 to 9 days. Finally, the higher polyurethane phase segregation also improved composite mechanical properties, as evidenced in stress-strain experiments and dynamic mechanical analysis.

Toluidine blue: aggregation properties and structural aspects

The toluidine blue (TB) aggregation phenomenon in water solutions was investigated by UV-Vis absorption spectroscopy in a wide range of concentrations, from 10−9 to 10−2 M. The experimental data were fitted by assuming that the spectrum was due to the overlapping of the bands of six different aggregation species simultaneously present in solution. The model and the peak centres of the different species were hypothesized on the basis of exciton theory. All the spectra obtained were simultaneously processed thus allowing the derivation of the K constant, which was assumed to be the same for all the equilibria and which was found equal to 10 500. The e spectra of the different aggregation species were also obtained. The overall TB spectrum may be mainly attributed to the H-type aggregation, although some of the species also show the J type bands. The structural features of TB and its dimeric aggregate were also investigated by means of molecular mechanics semi-empirical potential energy calculations. The results obtained for the dimer confirm the H type aggregation and show that the lowest energy model of the four possible is the one obtained by a mirror plane of symmetry containing the aromatic rings, in agreement with the x-ray diffraction data which will be presented in a forthcoming paper.

Pore formers promoted release of an antifungal drug from functionalized polyurethanes to inhibit Candida colonization.

Aims:  As a preventive strategy to inhibit fungal biofilm formation on medical devices, we planned experiments based on polyurethane loading with fluconazole plus pore‐former agents in order to obtain a promoted release of the antifungal drug.

Design and characterization of antimicrobial usnic acid loaded-core/shell magnetic nanoparticles

The application of magnetic nanoparticles (MNPs) in medicine is considered much promising especially because they can be handled and directed to specific body sites by external magnetic fields. MNPs have been investigated in magnetic resonance imaging, hyperthermia and drug targeting. In this study, properly functionalized core/shell MNPs with antimicrobial properties were developed to be used for the prevention and treatment of medical device-related infections. Particularly, surface-engineered manganese iron oxide MNPs, produced by a micro-emulsion method, were coated with two different polymers and loaded with usnic acid (UA), a dibenzofuran natural extract possessing antimicrobial activity. Between the two polymer coatings, the one based on an intrinsically antimicrobial cationic polyacrylamide (pAcDED) resulted to be able to provide MNPs with proper magnetic properties and basic groups for UA loading. Thanks to the establishment of acid-base interactions, pAcDED-coated MNPs were able to load and release significant drug amounts resulting in good antimicrobial properties versus Staphylococcus epidermidis (MIC = 0.1 mg/mL). The use of pAcDED having intrinsic antimicrobial activity as MNP coating in combination with UA likely contributed to obtain an enhanced antimicrobial effect. The developed drug-loaded MNPs could be injected in the patient soon after device implantation to prevent biofilm formation, or, later, in presence of signs of infection to treat the biofilm grown on the device surfaces.

Lipase Immobilization on Differently Functionalized Vinyl-Based Amphiphilic Polymers: Influence of Phase Segregation on the Enzyme Hydrolytic Activity

Microbial lipase from Candida rugosa was immobilized by physical adsorption onto an ethylene-vinyl alcohol polymer (EVAL) functionalized with acyl chlorides. To evaluate the influence of the reagent chain-length on the amount and activity of immobilized lipase, three differently long aliphatic fatty acids were employed (C8, C12, C18), obtaining EVAL functionalization degrees ranging from 5% to 65%. The enzyme-polymer affinity increased with both the length of the alkyl chain and the matrix hydrophobicity. In particular, the esterified polymers showed a tendency to give segregated hydrophilic and hydrophobic domains. It was observed the formation of an enzyme multilayer at both low and high protein concentrations. Desorption experiments showed that Candida rugosa lipase may be adsorbed in a closed form on the polymer hydrophilic domains and in an open, active structure on the hydrophobic ones. The best results were found for the EVAL-C18 13% matrix that showed hyperactivation with both the soluble and unsoluble substrate after enzyme desorption. In addition, this supported biocatalyst retained its activity for repetitive cycles.

Antifouling polyurethanes to fight device-related staphylococcal infections: synthesis, characterization and antibiofilm efficacy

In hospital settings, biofilm-based medical device-related infections are considered a threat to patients, the sessile growing bacteria playing a key role in the spreading of healthcare-associated infections. In recent decades, the design of antifouling coatings for medical devices able to prevent microbial adhesiveness has emerged as one of the most promising strategies to face this important issue. In order to obtain suitable antifouling materials, segmented polyurethanes characterized by a hard/soft domain structure, having the same hard domain but a variable soft domain, have been synthesized. The soft domain was constituted by one of the following macrodiols: polypropylenoxide (PPO), polycaprolactide (PCL), and poly-l-lactide (PLA). The effects of the polymer hydrophilicity and the degree of hard/soft domain separation on antifouling properties of the synthesized polyurethanes were investigated. Microbial adherence assays evidenced as the polymers containing PCL or PLA were able to significantly reduce the adhesion of Staphylococcus epidermidis with respect to the PPO-containing polymer.

Poly(p‐phenylene sulfide) Isothermal Cold Crystallization Investigated by Usual and Unusual Methods

In this paper we want to report the results obtained in our study of the cold-crystallization kinetics of PPS samples quenched from the melt state and analyzed in the crystallization temperature range 90–112°C. Such a wide range was explored by employing three different experimental techniques: the first one was the usual Differential Scanning Calorimetry (DSC), for the highest temperature range, the second and third ones were the less conventional FT-IR spectroscopy and energy dispersive X-ray diffraction (EDXD), able to explore the lowest temperature range. The experimental data obtained by the three above mentioned methods have been all together analyzed by means of the Avrami equation. FT-IR and EDXD have also allowed us to study the secondary crystallization process of PPS, which otherwise could not be observed just with the DSC technique. The overall crystallization process of such a polymer has been interpreted in the light of the model proposed by Ravindranath and Jog to explain the crystallization of the polymer from the melt state.

Poly(p-phenylene sulfide) glass transition temperature evidenced by IR spectroscopy

Abstract The glass transition of poly(phenylene sulfide) (PPS) has been examined by Fourier transform infrared spectroscopy (FT-IR). The relative absorbances A 1470 A 1072 , A 1383 A 1072 , A 1091 A 1072 and A 1009 A 1072 vs temperature showed a change of the slope at T = 75 °C, corresponding to the glass transition temperature of PPS when heated at 0.5 K/min. The results obtained have been discussed in the light of the possible causes.