Reinforcement of Acrylamide Hydrogels with Cellulose Nanocrystals Using Gamma Radiation for Antibiotic Drug Delivery.

In this paper, we report the synthesis of acrylamide hydrogels (net-AAm) reinforced with cellulose nanocrystals (CNCs) using gamma radiation, a powerful tool to obtain crosslinked polymers without the use of chemical initiators and crosslinking agents. Some slight changes in the chemical structure and crystallinity of CNCs took place during gamma irradiation without affecting the nanofiller function. In fact, cellulose nanocrystals had a notable influence over the swelling and mechanical properties on the reinforced hydrogels (net-AAm/CNC), obtaining more rigid material since the Young compression modulus increased from 11 kPa for unreinforced net-AAm to 30 kPa for net-AAm/CNC (4% w/w). Moreover, the studies of retention and release of ciprofloxacin (Cx), a quinolone antibiotic drug, showed that reinforced hydrogels were able to load large amounts of ciprofloxacin (1.2-2.8 mg g-1) but they distributed 100% of the drug very quickly (<100 min). Despite this, they exhibited better mechanical properties than the control sample, allowing their handling, and could be used as wound dressings of first response because they can absorb the exudate and at the same time deliver an antibiotic drug directly over the injury.

Development of Polyphenol-Functionalized Gelatin-Poly(vinylpyrrolidone) IPN for Potential Biomedical Applications.

Owing to their suitable physical and chemical properties, hydrogels have been considered a convenient choice for wound dressings because of the advantages that they offer, such as maintaining the moist environment required for wound healing. In this research, interpenetrating hydrogels of polyphenol-functionalized gelatin (GE), a water-soluble protein derived from natural polymer collagen with excellent biocompatibility, no immunogenicity, and hydrophilicity, and polyvinylpyrrolidone (PVP), a hydrophilic, non-toxic, biodegradable, biocompatible polymer that is soluble in many solvents, widely used in biomedical applications, particularly as a basic material for the manufacturing of hydrogel wound dressings, were synthesized. Gallic acid (GA) was selected in this work to study whether the interpenetrating polymer networks (IPNs) synthesized can provide antioxidant properties given that this material is intended to be used as a potential wound dressing. The obtained IPN hydrogels showed improved mechanical properties in comparison with pristine gelatin network (net-GE), a porous structure, and good thermal stability for biological applications. The antioxidant capacity of the IPNs functionalized with GA was compared to Trolox standards, obtaining a radical scavenging activity (RSA%) equivalent to a Trolox concentration of 400 µM.

Binary Graft of Poly(N-vinylcaprolactam) and Poly(acrylic acid) onto Chitosan Hydrogels Using Ionizing Radiation for the Retention and Controlled Release of Therapeutic Compounds.

In this study, we carried out the synthesis of a thermo- and pH-sensitive binary graft, based on N-vinylcaprolactam (NVCL) and pH sensitive acrylic acid (AAc) monomers, onto chitosan gels (net-CS) by ionizing radiation. Pre-oxidative irradiation and direct methods were examined, and materials obtained were characterized by FTIR-ATR, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and swelling tests (equilibrium swelling time, critical pH, and temperature). The best synthesis radiation method was the direct method, which resulted in the maximum grafting percentages (~40%) at low doses (10-12 kGy). The main goal of this study was the comparison of the swelling behavior and physicochemical properties of net-CS with those of the binary system (net-CS)-g-NVCL/AAc with the optimum grafting percentage (~30%). This produced a material that showed an upper critical solution temperature (UCST) of 33.5 °C and a critical pH value of 3.8, indicating the system is more hydrophilic at higher temperatures and low pH values. Load and release studies were carried out using diclofenac. The grafted system (32%) was able to load 19.3 mg g-1 of diclofenac and release about 95% within 200 min, in comparison to net-CS, which only released 80% during the same period. When the grafted system was protonated before diclofenac loading, it loaded 27.6 mg g-1. However, the drug was strongly retained in the material by electrostatic interactions and only released about 20%.

Chitosan hydrogel synthesis to remove arsenic and fluoride ions from groundwater.

Groundwater samples from eight deep drinking water wells that cover three aquifers in Chihuahua City, northern Mexico, were fully characterized. Water is naturally contaminated with arsenic, fluoride, and uranium, according to the Environmental Protection Agency (EPA) and local standards. The results from the Geochemist's Workbench (GWB) program revealed that the minerals in equilibrium with the groundwater were calcite and dolomite, while others, such as fluoride, schoepite, rutherfordite and K(UO2)(AsO4), were also dissolved. The hydrogeochemical characterization of water samples indicates that they were sodium bicarbonate-type water samples at neutral to slightly alkaline pH (7.6-8.3). A batch equilibrium sorption procedure was implemented using natural groundwater, a synthesized chitosan network (net-CS) and a chitosan binary network grafted with N-vinylcaprolactam/N-N-dimethylacrylamide (net-CS)-g-NVCL/DMAAm hydrogels. Isotherms and kinetics sorption tests were evaluated. The adsorption capacity of net-CS hydrogels for As ions was 0.0022 mg/g and F ions 0.15 mg/g after 50 h. Scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS) was used to investigate the hydrogel surface before and after the sorption process, and TGA was used to evaluate the stability of the adsorbents. Freundlich adsorption isotherm constants for As and F ions indicate heterogeneous sorption and the mechanism of retention by physisorption.

Obtainment and Characterization of Hydrophilic Polysulfone Membranes by N-Vinylimidazole Grafting Induced by Gamma Irradiation.

Polysulfone (PSU) film and N-vinylimidazole (VIM) were used to obtain grafted membranes with high hydrophilic capacity. The grafting process was performed by gamma irradiation under two experiments: (1) different irradiation doses (100-400 kGy) and VIM 50% solution; (2) different concentration of grafted VIM (30-70%) and 300 kGy of irradiation dose. Characteristics of the grafted membranes were determined by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle, swelling degree, desalination test, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Both experiments indicated that the absorbed dose 300 kGy and the VIM concentration, at 50% v/v, were effective to obtain PSU grafted membranes with 14.3% of grafting yield. Nevertheless, experimental conditions, 400 kGy, VIM 50% and 300 kGy, VIM 60-70% promoted possible membrane degradation and VIM homopolymerization on the membrane surface, which was observed by SEM images; meanwhile, 100-200 kGy and VIM 30-50% produced minimal grafting (2 ± 0.5%). Hydrophilic surface of the grafted PSU membranes by 300 kGy and VIM 50% v/v were corroborated by the water contact angle, swelling degree and desalination test, showing a decrease from 90.7° ± 0.3 (PSU film) to 64.3° ± 0.5; an increment of swelling degree of 25 ± 1%, and a rejection-permeation capacity of 75 ± 2%. In addition, the thermal behavior of grafted PSU membranes registered an increment in the degradation of 20%, due to the presence of VIM. However, the normal temperature of the membrane operation did not affect this result; meanwhile, the glass transition temperature (Tg) of the grafted PSU membrane was found at 185.4 ± 0.5 °C, which indicated an increment of 15 ± 1%.

Effect of Ionizing Radiation on the Chemical Structure and the Physical Properties of Polycaprolactones of Different Molecular Weight.

Polymers used in the biomedical sector can be exposed to ionizing radiation (X-ray, gamma) in vivo as implants or ex vivo for sterilization purposes (gamma, electron beam). This ionizing radiation can, at certain levels, cause degradation of the polymer. Polycaprolactones (PCL) of different molecular weights were irradiated with electron beam and the changes in their chemical structure and physical properties with the dose were evaluated. Electron beam irradiation produced crosslinking and chain scission in the PCL chain without significant predominance of one mechanism over the other. Minimum dose for gelation decreased with the increase in PCL molecular weight whereas crosslinking efficiency was almost independent of PCL molecular weight. Carboxylic groups, hydroxyl groups and new saturated hydrocarbon species were detected by proton nuclear magnetic resonance (NMR). These species were consistent with a mechanism where chain scission could take place at any bond in the PCL chain with preference in the ⁻COO⁻CH2⁻ bond. Crosslinking decreased significantly the crystallization temperature of PCL. Tensile properties decreased continuously with the increase in dose. Irradiation with gamma rays produced a faster decay in mechanical properties than electron beam.

Radiation grafting of N-vinylcaprolactam onto nano and macrogels of chitosan: Synthesis and characterization.

The aim of this study was to synthesize chitosan hydrogels, in macro- and nano-size, grafted with N-vinylcaprolactam (NVCL) using gamma radiation, and evaluate their potential application as a drug delivery system, using 5-fluorouracil (5-FU) as a model drug. The effect of dose and monomer concentration in the grafting process was studied, and the materials were characterized by FTIR, TGA, DLS, SEM and AFM. Higher grafting percentages were observed for the nanogels system. Although both the grafted macro- and nanogels, (net-CS)-g-NVCL, showed a response to pH (4.75) and temperature (31-33°C), the nanogels showed a better swelling response to both stimuli because of their higher surface area. Both systems were able to load 5-FU in small amounts (2-3.5mgg-1) and the release was sustained for more than 12h, showing that the modified macro and nanogels can be a potential alternative for the administration of drugs.

Mucoadhesive thermo-responsive chitosan-g-poly(N-isopropylacrylamide) polymeric micelles via a one-pot gamma-radiation-assisted pathway.

Thermo-sensitive graft copolymer amphiphiles of chitosan (CS) and poly(N-isopropylacrylamide) (PNiPAAm), CS-g-PNIPAAm, were successfully synthesized by a catalyst-less one-pot gamma (γ)-radiation-assisted free radical polymerization at three different radiation doses: 5, 10 and 20 kGy. The chemical structure of the copolymers was confirmed by FTIR and solid-state (13)C NMR and the grafting extent by (1)H NMR and gravimetric analysis. In general, the higher the dose, the smaller the grafting due to the more significant NiPAAm homopolymerization. Due to the grafting of poly(NiPAAm) blocks, aqueous solutions of the different copolymers underwent a sharp transition upon heating above 32 °C, the characteristic lower critical solution temperature (LCST) of poly(NiPAAm). Then, the critical micellar concentration (CMC), the size and size distribution and the zeta-potential were characterized by dynamic light scattering (DLS) and the polymeric micelles visualized in suspension and quantified by Nanoparticle Tracking Analysis (NTA), at 37 °C. CMC values were in the 0.0012-0.0025%w/v range and micelles displayed sizes between 99 and 203 nm with low polydispersity (<0.160) and highly positive zeta-potential (>+15 mV) that suggested the partial conservation of the amine groups upon NiPAAm grafting. Consequently, polymeric micelles displayed the intrinsic mucoadhesiveness of CS, as established in vitro by the mucin solution assay. Finally, the encapsulation capacity of the micelles was assessed with the highly hydrophobic protease inhibitor antiretroviral indinavir free base (IDV). Polymeric micelles led to a significant 24-fold increase of the aqueous solubility from 63 µg/mL to 1.45 mg/mL, a performance remarkably better than different poly(ethylene oxide)-b-poly(propylene oxide) block copolymers assessed before. Overall results highlight the potential of this nanotechnology platform to expand the application of polymeric micelles to mucosal administration routes.

Singly and binary grafted poly(vinyl chloride) urinary catheters that elute ciprofloxacin and prevent bacteria adhesion.

Acrylic acid (AAc) and poly(ethylene glycol) methacrylate (PEGMA) were singly and dually grafted onto poly(vinyl chloride) (PVC) urinary catheters with the aim of preventing biofouling by endowing the catheters with the ability to load and release antimicrobial agents and to avoid bacteria adhesion. The polymers were grafted applying an oxidative pre-irradiation ((60)Co source) method in two steps. Grafting percentage and kinetics were evaluated by varying the absorbed pre-irradiation dose, reaction time, monomer concentration, and reaction temperature. Catheters with grafting percentages ranging from 8 to 207% were characterized regarding thermal stability, surface hydrophilicity, mechanical properties, swelling, and lubricity. The modified catheters proved to have better compatibility with fibroblast cells than PVC after long exposure times. Furthermore, grafted catheters were able to load ciprofloxacin and sustained its release in urine medium for several hours. Ciprofloxacin-loaded catheters inhibited the growth of Escherichia coli and Staphylococcus aureus in the catheter surroundings and prevented bacteria adhesion.

Materials with fungi-bioinspired surface for efficient binding and fungi-sensitive release of antifungal agents.

Materials with fungi-bioinspired surface have been designed to host ergosterol-binding polyene antibiotics and to release them via a competitive mechanism only when fungi are present in the medium. Silicone rubber (SR) surfaces were endowed with selective loading and fungi-triggered release of polyene antifungal agents by means of a two-step functionalization that involved the grafting of glycidyl methacrylate (GMA) via a γ-ray preirradiation method (9-21.3% wt grafting) and the subsequent immobilization of ergosterol (3.9-116.8 mg/g) to the epoxy groups of polyGMA. The functionalized materials were characterized using FTIR and Raman spectroscopy, thermogravimetric analysis (TGA), and fluorescence, scanning electron microscopy (SEM), and atomic force microscopy (AFM) image analyses. Specific interactions between natamycin or nystatin and ergosterol endowed SR with ability to take up these polyene drugs, while immobilization of ergosterol did not modify the loading of antifungal drugs that did not interact in vivo with ergosterol (e.g., miconazole). In a buffer medium, polyene-loaded ergosterol-immobilized slabs efficiently retained the drug (<10% released at day 14), while in the presence of ergosterol-containing liposomes that mimic fungi membranes the release rate was 10-to-15-fold enhanced due to a competitive displacement of the drug from the ergosterol-immobilized slab to the ergosterol-containing liposomes. Release in the presence of cholesterol liposomes was slower due to a weaker interaction with polyene agents. The fungi-responsive release was demonstrated for both polyene drugs tested and for slabs prepared with a wide range of amounts of immobilized GMA and ergosterol, demonstrating the robustness of the approach. Nystatin-loaded functionalized slabs were challenged with Candida albicans and showed improved capability to inhibit biofilm formation compared to nystatin-soaked pristine SR, confirming the performance of the bioinspired materials.

Unexpected absorbance enhancement upon clustering dyes in a polymer matrix.

PE films grafted with poly(methyl acrylate) and labeled with pyrene groups were obtained by irradiation with γ-rays in the presence of acryloyl chloride and further reacting them with 1-pyrenebutanol or 1-pyrenemethylamine. Characterization of the polymer films benefited from the dual use of the pyrene probe as an indicator of, first, polymer chain dynamics by monitoring pyrene excimer formation by fluorescence and, second, polymer morphology by staining the pyrene-rich domains of the films with RuO(4) for scanning electron microscopy (SEM). The grafted polymers labeled with 1-pyrenemethylamine showed much stronger absorbance than those labeled with 1-pyrenebutanol despite having similar pyrene contents. The fluorescence spectra of the grafted polymers labeled with 1-pyrenebutanol exhibited monomer emission, whereas those labeled with 1-pyrenemethylamine exhibited exclusively excimer emission. These dramatic differences could be accounted for by noting that labeling of the grafted poly(acryloyl chloride) with 1-pyrenemethylamine results in cross-linking of the polymer matrix, with an associated enhancement of the concentration of pyrene in the cross-linked domains, which was confirmed by SEM. Formation of discrete domains in the polymer film can induce multiple scattering at the domain boundaries which lengthens the path of light in the film and increases absorption of the light by the tightly packed pyrene-rich domains. Implementation of this effect for fabrication of plastic color filters should generate more efficient filters which should find numerous practical applications.

Medical devices modified at the surface by gamma-ray grafting for drug loading and delivery.

IMPORTANCE OF THE FIELD: Medical devices with the capability of hosting drugs are being sought for prophylaxis and treatment of inflammatory response and microbial colonization and proliferation that are associated with their use. AREAS COVERED IN THIS REVIEW: This review analyzes the interest of gamma-ray irradiation for providing medical devices with surfaces able to load drugs and to deliver them in a controlled way. The papers published in the last 20 years on the subject of gamma-ray irradiation methods for surface functionalization of polymers and their application for developing medicated medical devices are discussed. WHAT THE READER WILL GAIN: The information reported may help to gain insight to the state-of-the-art of gamma-ray irradiation approaches and their current advantages/limitations for tailoring the surface of medical devices to fit preventive and curative demands. TAKE HOME MESSAGE: Grafting of polymer chains able to establish specific interactions with the drug, grafting of stimuli-responsive networks that regulate drug diffusion through the hydrogel-type surface as a function of the surrounding conditions, and grafting of cyclodextrins that control uptake and delivery through the affinity constant of inclusion complexes have been revealed as efficient approaches for endowing medical devices with the capability of also acting as drug delivery systems.

Cyclodextrin-functionalized biomaterials loaded with miconazole prevent Candida albicans biofilm formation in vitro.

Polyethylene (PE) and polypropylene (PP) were functionalized at their surfaces with cyclodextrins (CDs) in order to prevent the adhesion and proliferation of Candida albicans on medical devices made from these polymers. The surface functionalization involved the grafting of glycidyl methacrylate (GMA) after oxidative gamma-ray pre-irradiation, followed by the attachment of beta-CD and HP-beta-CD to PE-g-GMA and PP-g-GMA surfaces. The yield of CD functionalization directly depended on the amount of GMA grafted. The presence of CDs on the surface of the polymers did not compromise their cell compatibility, but remarkably changed their protein adsorption profile. In contrast to unmodified PE and PP that adsorb significant amounts of fibrinogen ( approximately 0.047 mg cm(-2)) but not albumin, the CD-modified polyethers promoted the adsorption of albumin (between 0.015 and 0.155 mg cm(-2)) and reduced the adsorption of fibrinogen. Furthermore, functionalization with CDs provided PE and PP with the capability to incorporate the anti-fungal drug miconazole (up to 0.27 mg cm(-2)), leading to reduced biofilm formation by C. albicans in an in vitro biofilm model system. Overall, the results of the work indicate that the novel approach for functionalization of PE and PP is potentially useful to reduce the likelihood of foreign body-related infections.

Cyclodextrin-functionalized polyethylene and polypropylene as biocompatible materials for diclofenac delivery.

Polyethylene (PE) and polypropylene (PP) were surface functionalized with beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with the aim of providing PE and PP with the capability of behaving as drug delivery systems. Functionalization was carried out according to a two-step procedure: (i) glycidyl methacrylate (GMA) was grafted by means of gamma radiation and (ii) the epoxy groups of GMA reacted with the hydroxyl groups of CDs forming ether bonds. For a fix radiation dose and GMA concentration, grafting yield (ranging from 1 to 100 micromol GMA cm(-2)) depended on the time during which the preirradiated PE and PP films and slabs were immersed in the GMA solution. CD grafting (from 0.013 to 0.734 micromol cm(-2)) was confirmed by infrared analysis, DSC and the organic compound approach (using 3-methylbenzoic acid as a probe). Functionalization with CDs rendered as highly cytocompatible materials as the starting ones, did not cause relevant changes in the water contact angle and the friction coefficient of PE and PP, but remarkably improved their capability to uptake diclofenac through formation of inclusion complexes with the CDs. Furthermore, the functionalized materials released the drug for 1 h, which could be useful for management of initial pain, inflammation at the insertion site as well as adhesion of certain microorganisms if these materials are used as medicated medical devices.

Polypropylene grafted with smart polymers (PNIPAAm/PAAc) for loading and controlled release of vancomycin.

New smart surface-modified polypropylene (PP) was prepared for improving the loading and the sustained delivery of vancomycin and, thus, reducing the risk of biofilm formation when used as component of biomedical devices. Isothermal titration calorimetry (ITC) served for screening the most suitable monomers for grafting; the drug preferentially bonding to ionized acrylic acid (AAc). A net-PP-g-PNIPAAm-inter-net-PAAc was synthesized by first grafting and cross-linking of N-isopropylacrylamide onto PP films and then interpenetrating a second network by redox polymerization and cross-linking of AAc. PP-g-PAAc slabs were prepared by grafting AAc and, optionally, cross-linking. The amount and composition of grafted polymer (FTIR-ATR), morphology (SEM), temperature- and pH-responsiveness (swelling measurements), thermal behavior (DSC), friction coefficient (rheometry), drug loading and release rate, and effect against methicillin-resistant Staphylococcus aureus (MRSA) biofilms (modified robbins device) were evaluated. Grafting of AAc notably decreased the friction coefficient from 0.28+/-0.03 to 0.05+/-0.02 and enhanced the vancomycin loading (up to 2.5mg/cm(2)). Drug-loaded films showed a pH-dependent release rate, sustaining the release in pH 7.4 aqueous media at 37 degrees C for several hours. All drug-loaded films reduced biofilm formation by MRSA; the anti-biofilm effect being statistically significant (91.7% reduction, alpha<0.05) for PP-g-PAAc with the thinnest grafting layer.

Immobilization of streptavidin-horseradish peroxidase onto a biotinylated poly(acrylic acid) backbone that had been radiation-grafted to a PTFE film.

Films of polytetrafluoroethylene (PTFE) were modified by radiation graft polymerization of acrylic acid (AAc). Optimal conditions for efficient AAc grafting were studied, including pre-irradiation dose in air, monomer concentration, temperature and time of the grafting process. Carboxylic groups of the grafted polyAAc were activated with carbodiimide (EDC) for biotinylation by reaction with 5-(biotinamido) pentylamine. Streptavidin-horseradish peroxidase (SA-HRP) was immobilized by affinity complexation of the SA with the biotin groups on the PTFE surface. The amount of active HRP immobilized on the PTFE films was determined as a function of the extent of polyAAc grafting. This study has demonstrated the utility of combining the processes of (a) radiation grafting of polymers with reactive groups onto inert polymers such as PTFE, (b) biotinylation of the graft polymer reactive groups, (c) immobilization of streptavidin on the biotinylated surface sites, followed by (d) immobilization of biotinylated, biologically active molecules via complexation of their conjugates with streptavidin. In this study, the last two steps were combined by immobilizing the complex of streptavidin and biotinylated HRP onto the biotinylated surface sites. The unique nature of this process is the ability to immobilize biotinylated molecules on an inert surface as PTFE.