László Janovák

Silver and phosphate functionalized reactive TiO 2/polymer composite films for destructions of resistent bacteria using visible light

Abstract Phosphate and silver co-functionalized TiO2 catalysts were prepared by varying amount of silver (0-1 wt.%) with constant phosphate content (0.25 wt.%). Two methods, the well-know photodeposition and a new simple method, i.e. heterocoagulation, are presented for preparing Ag-TiO2 and the optical, photochemical and photobiological properties of the different samples have been compared. Due to the silver modification, the photocatalysts showed a new Plasmon resonance peak at λmax= 455 nm. The photocatalytic efficiencies of the new photo catalysts were studied under UV-A/visible (λ > 360 nm) irradiation. Mechanically stable hydrophilic poly(EA-co-MMA) and hydrophobic poly(Bi.A-co-Ech.) based composite films were prepared by spray coating technique. The photocatalytic efficiencies decreased only by ~ 15% on the hydrophilic and ~ 63% on the hydrophobic polymer compared to the reference pure photocatalyst films. The antibacterial activity of the films was also studied under visible light (λ > 400 nm) irradiation. Methicillin resistant Staphylococcus aureus (MRSA) was used as test bacterium. The best antibacterial activity (90% of bacteria destruction in 15 minutes) could be observed on the Ag- TiO2/p(EA-co-MMA) film.

Investigation of the in vitro photocatalytic antibacterial activity of nanocrystalline TiO2 and coupled TiO2/Ag containing copolymer on the surface of medical grade titanium

Antibacterial surfaces have been in the focus of research for years, driven by an unmet clinical need to manage an increasing incidence of implant-associated infections. The use of silver has become a topic of interest because of its proven broad-spectrum antibacterial activity and track record as a coating agent of soft tissue implants and catheters. However, for the time being, the translation of these technological achievements for the improvement of the antibacterial property of hard tissue titanium (Ti) implants remains unsolved. In our study, we focused on the investigation of the photocatalysis mediated antibacterial activity of silver (Ag), and Ti nanoparticles instead of their pharmacological effects. We found that the photosensitisation of commercially pure titanium discs by coating them with an acrylate-based copolymer that embeds coupled Ag/Ti nanoparticles can initiate the photocatalytic decomposition of adsorbed S. salivarius after the irradiation with an ordinary visible light source. The clinical isolate of S. salivarius was characterised with MALDI-TOF mass spectrometer, while the multiplication of the bacteria on the surface of the discs was followed-up by MTT assay. Concerning practical relevance, the infected implant surfaces can be made accessible and irradiated by dental curing units with LED and plasma arc light sources, our research suggests that photocatalytic copolymer coating films may offer a promising solution for the improvement of the antibacterial properties of dental implants.

Spherical LDH-Ag°-montmorillonite heterocoagulated system with a pH-dependent sol-gel structure for controlled accessibility of AgNPs immobilized on the clay lamellae.

Aqueous suspensions of spherical ZnMgAl-layered double hydroxides [LDH(sph)] and antibacterial silver nanoparticles (AgNPs) deposited on the lamellae of montmorillonite were used for the synthesis of composites, which behave like coherent gels at low pH (≲4.5) and incoherent sols at higher pH (≳4.5). The composition of the composite was chosen as LDH(sph)/Ag°-montm. = 25:75 wt % in order to ensure a sol-gel transition that can also be characterized by viscometry. This pH-sensitive heterocoagulated system consisting of oppositely charged colloid particles was suitable for the release of antimicrobial AgNPs immobilized on the clay lamellae via a pH-controlled gel-sol transition. The heterocoagulation process was also characterized by surface charge titration measurements. Spherical LDH/Ag°-montmorillonite composite samples were identified by X-ray diffraction (XRD) measurements. The morphological properties of the composites were studied, and the presence of the heterocoagulated structure was confirmed by scanning electron microscopy (SEM). The nanoscale structure of the LDH(sph)-Ag°-montmorillonite composite obtained was also verified by small-angle X-ray scattering (SAXS), and the rheological characteristics were studied at various pH values. The viscosity and yield value of the composite decreased by an order of magnitude upon increasing the pH from 3.0 to 5.5. The sol-gel transition of the composite suspension was reversible in the previously mentioned pH range.

LED-light activated antibacterial surfaces using silver-modified TiOembedded in polymer matrix

Abstract Silver functionalized TiO2/poly(etyl-acrylate co methyl-methacrylate) nanohybrid films were proved to inactivate nosocomial bacteria. The films were prepared on glass plates by spray coating technique and their thickness were 1.48±0.1 μm. During photocatalysis, the films were illuminated with visible LED-light source (λ = 405 nm). The optical and photooxidation properties of prepared nanocomposite films were characterized by diffuse reflectance measurements and the photocatalytic properties were tested in ethanol photooxidation monitored by gas-chromatography experiments. The photocatalytic activity of the nanohybrid films were tested under visible light illumination against bacteria causing nosocomial infections, such as methicillin resistant Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa and Acinetobacter baumannii. The investigation of the antibacterial activity of the silver functionalized TiO2 was carried out by measuring the survival ratio of the original amount of the bacteria on the nutrient agar plate. To verify the photooxidation effect of the reactive films, parallel experiments were carried out without any light source. All of the investigated bacteria were inactivated on the surface of the nanohybrid films within 120 minutes of LED-light illumination.

Acrylamide, acrylic acid and N-isopropylacrylamide hydrogels as osmotic tissue expanders.

Background and Aim: Osmotically active tissue expanders allow the harvesting of soft tissue for reconstruction after different injuries. However, their expansion properties could be improved. Thus, our goal was to examine the in vivo applicability of acrylamide (AAm), acrylic acid (AAc) and N- isopropylacrylamide (NIPAAm) hydrogels. Materials and Methods: Cylinders of AAm, AAc and NIPAAm hydrogels were implanted under the skin of rats in the dorsal region. The diameter and the length of the cylinders were measured daily. After removal of the hydrogels, their mass and rheological properties were determined. Further, biopsies were taken from the adjacent tissue for histological analysis. Results: The hydrogels reached the peak of swelling by the end of the 2nd postoperative week. The wet mass of the removed cylinders was 25 times their dry mass prior to implantation. NIPAAm polymers exhibited the most favourable visco-elastic properties, with the highest tendency to retain their preformed shape. The histological analysis revealed serious tissue damage when the AAc devices were used, whereas the AAm and NIPAAm did not result in such lesions. Conclusion: In view of its mechanical and biological properties, NIPAAm hydrogel seems to be the most appropriate of these materials for application in plastic and reconstructive surgery.

Stressors alter intercellular communication and exosome profile of nasopharyngeal carcinoma cells.

BACKGROUND Head and neck cancers comprise the sixth most common cancer type worldwide. One of the most remarkable malignancies of the head and neck is the cancer of the nasopharynx, with a strong metastatic tendency already in the early stage. Besides the conventional pathways of metastasis formation, the information content of exosomes produced by the cancer cells may play a key role in metastatic transformation. The aim of this study was to investigate how stressors alter the characteristic of tumor derived exosomes. METHODS In our experimental model, we compared the quantity and content of exosomes produced by a nasopharyngeal carcinoma cell line (5-8F) under conventional (chemotherapy) and alternative (Ag-TiO2 -catalyzed reactive oxygen species generation) cytostatic treatment. After isolation, exosomes were identified by atomic force microscopy and quantified with Nanosight NS500 device. MicroRNA content of them was analyzed using SOLiD 5500xl technology. The sequences were annotated in CLC Genomics Workbench version 5.5.1. RESULTS Beyond the classic chemotherapeutic agent (doxorubicin), Ag-TiO2 in a photo-catalytic process also showed cytostatic activity. Tumor cell damage induced by the cytostatic treatments significantly altered the number of released exosomes and led to the predominance of tumor suppressors in the exosomal miRNA profile. CONCLUSIONS Our results suggest that the intercellular communication between tumor cells and surrounding stroma cells can be altered by microenvironment which increased quantity of exosomes and diversity of miRNAs in this study. Imbalance of oncogenic and tumor suppressor miRNAs caused by cytostatic treatments may influence the antiproliferative and metastasis inhibitory effect of cytostatic agents.

Preparation and Antibacterial Properties of Reactive Surface Coatings Using Solar Energy Driven Photocatalyst

Interdisciplinary researches of nanotechnology and microbiology have become great interest to develop environmental applications against bacteria causing nosocomial infections. Antimicrobial applications are able to inactivate bacteria, viruses, and fungi on different surfaces, in water or in the air, so they can be the main factor of prevention in the health-care facilities. Functional surfaces with UV or visible light–active photocatalyst content can kill numerous microorganisms because of its photocatalytic properties. Due to the appearance of reactive radicals, the photocatalyst particles can degrade many organic compounds and inactivate microorganisms via destroying the cell wall and their DNA, respectively. Due to these properties, a wide range of pathogen bacteria can be inactivated under visible light illumination. Besides the photocatalytic thin films, superhydrophobic coatings belong to the second class of self-cleaning and antibacterial surfaces. Superhydrophobic surfaces, with a liquid contact angle larger than 150 degrees, have important practical applications ranging from self-cleaning surfaces and antibacterial coatings. It is also presented that the advantageous properties of the photocatalytic and superhydrophobic surfaces can also combine.

Preparation of novel tissue acidosis-responsive chitosan drug nanoparticles: Characterization and in vitro release properties of Ca2+ channel blocker nimodipine drug molecules

ABSTRACT The pH‐responsive intelligent drug release facility of hydrophobically modified chitosan nanoparticles (Chit NPs) (d = 5.2 ± 1.1 nm) was presented in the case of poorly water soluble Ca2+ channel blocker nimodipine (NIMO) drug molecules. The adequate pH‐sensitivity, i.e. the suitable drug carrier properties of the initial hydrophilic Chit were achieved by reductive amination of Chit with hexanal (C6‐) and dodecanal (C12‐) aldehydes. The successful modifications of the macromolecule were evidenced via FTIR measurements: the band appearing at 1412 cm−1 (C–N stretching in aliphatic amines) in the cases of the hydrophobically modified Chit samples shows that the C–N bond successfully formed between the Chit and the aldehydes. Hydrophobization of the polymer unambiguously led to lower water contents with lower intermolecular interactions in the prepared hydrogel matrix: the initial hydrophilic Chit has the highest water content (78.6 wt%) and the increasing hydrophobicity of the polymer resulted in decreasing water content (C6‐chit.: 74.2 wt% and C12‐chit.: 47.1 wt%). Furthermore, it was established that the length of the side chain of the aldehyde influences the pH‐dependent solubility properties of the Chit. Transparent homogenous polymer solution was obtained at lower pH, while at higher pH the formation of polymer (nano)particles was determined and the corresponding cut‐off pH values showed decreasing tendency with increasing hydrophobic feature (pH = 7.47, 6.73 and 2.49 for initial Chit, C6‐chit and C12‐chit, respectively). Next the poorly water soluble NIMO drug was encapsulated with the C6‐chit with adequate pH‐sensitive properties. The polymer‐stabilized NIMO particles with 10 wt% NIMO content resulted in stable dispersion in aqueous phase, the formation of polymer shell increased in the water solubility/dispersibility of the initial hydrophobic drug. According to the drug release experiments, we clearly confirmed that the encapsulated low crystallinity NIMO drug remained closed in the polymer NPs at normal tissue pH (pH = 7.4, PBS buffer, physiological condition) but at pH < 6.5 which is typical for seriously ischemic brain tissue, 93.6% of the available 0.14 mg/ml NIMO was released into the buffer solution under 8 h release time. According to this in vitro study, the presented pH‐sensitive drug carrier system could be useful to selectively target ischemic brain regions characterized by acidosis, to achieve neuroprotection at tissue zones at risk of injury, without any undesirable side effects caused by systemic drug administration. Graphical abstract Figure. No Caption available.

Cross-linked and hydrophobized hyaluronic acid-based controlled drug release systems

This work demonstrates the preparation, structural characterization, and the kinetics of the drug release of hyaluronic acid (HyA)-based colloidal drug delivery systems which contain hydrophobic ketoprofen (KP) as model molecule. Because of the highly hydrophilic character of HyA the cross-linked derivatives at different cross-linking ratio have been synthesized. The hydrophobized variants of HyA have also been produced by modifying the polymer chains with cetyltrimethylammonium bromide (CTAB) at various HyA/CTAB ratios. Due to modifications the coherent structure of HyA changes into an incoherent colloidal system that were verified by rheological investigations. Nearly 70% of the encapsulated KP dissolve from the totally cross-linked HyA carrier but the release rate of KP is about 20% (after 8 h) from the CTAB-modified colloidal system at HyA monomer/CTAB 1:0.8 mass ratio. It has been verified that the modified HyA may be a potential candidate for controlled drug release of hydrophobic KP molecules.

Contents Vol. 22, 2009

N. Ahmad, Madison, Wisc. P. Altmeyer, Bochum C. Antoniou, Athens H. Bachelez, Paris J.M. Baron, Aachen E. Benfeldt, Hellerup E. Berardesca, Rome D.R. Bickers, New York, N.Y. I. Bogdan Allemann, Zürich K. De Paepe, Brussels P. Elsner, Jena A. Farkas, Szeged A. Giannetti, Modena M.W. Greaves, London R.H. Guy, Bath J. Hadgraft , London E.M. Jackson, Bonney Lake, Wash. Y. Kawakubo, Chiba H.-C. Korting, Munich J. Krutmann, Düsseldorf R. Neubert, Halle D.R. Roop, Aurora, Colo. T. Ruzicka, Munich M. Schäfer-Korting, Berlin S. Seidenari, Modena B. Shroot, San Antonio, Tex. J. Wohlrab, Halle S. Yamamoto, Hiroshima Journal of Pharmacological and Biophysical Research