D. Cafagna

Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery

The aim of this study was to characterize nanoparticles (NPs) composed of chitosan (CS) and evaluate their potential for brain delivery of the neurotransmitter Dopamine (DA). For this purpose, CS based NPs were incubated with DA at two different concentrations giving rise to nanocarriers denoted as DA/CSNPs (1) and DA/CSNPs (5), respectively. X-ray Photoelectron Spectroscopy (XPS) analysis confirmed that DA was adsorbed onto the external surface of such NPs. The cytotoxic effect of the CSNPs and DA/CSNPs was assessed using the MTT test and it was found that the nanovectors are less cytotoxic than the neurotransmitter DA after 3 h of incubation time. Transport studies across MDCKII-MDR1 cell line showed that DA/CSNPs (5) give rise to a significant transport enhancing effect compared with the control and greater than the corresponding DA/CSNPs (1). Measurement of reactive oxygen species (ROS) suggested a low DA/CSNPs neurotoxicity after 3 h. In vivo brain microdialysis experiments in rat showed that intraperitoneal acute administration of DA/CSNPs (5) (6-12 mg/kg) induced a dose-dependent increase in striatal DA output. Thus, these CS nanoparticles represent an interesting technological platform for DA brain delivery and, hence, may be useful for Parkinsons disease treatment.

An innovative, easily fabricated, silver nanoparticle-based titanium implant coating: development and analytical characterization

AbstractMicrobial colonization and biofilm formation on implanted devices represent an important complication in orthopaedic and dental surgery and may result in implant failure. Controlled release of antibacterial agents directly at the implant site may represent an effective approach to treat these chronic complications. Resistance to conventional antibiotics by pathogenic bacteria has emerged in recent years as a major problem of public health. In order to overcome this problem, non-conventional antimicrobial agents have been under investigation. In this study, polyacrylate-based hydrogel thin coatings have been electrosynthesised on titanium substrates starting from poly(ethylene glycol diacrylate)–co–acrylic acid. Silver nanoparticles (AgNPs) with a narrow size distribution have been synthesized using a “green” procedure and immobilized on Ti implant surfaces exploiting hydrogel coatings’ swelling capabilities. The coatings have been characterized by XPS and SEM/EDX, while their silver release performances have been monitored by ICP–MS. The antibacterial activity of these AgNP-modified hydrogel coatings was tested evaluating in vitro inhibition growth of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, among the most common pathogens in orthopaedic infections. Moreover, a preliminary investigation of the biocompatibility of silver-loaded coatings versus MG63 human osteoblast-like cells has been performed. An important point of strength of this paper, in fact, is the concern about the effect of silver species on the surrounding cell system in implanted medical devices. Silver ion release has been properly tuned in order to assure antibacterial activity while preserving osteoblasts’ response at the implant interface. FigureSilver nanoparticles-loaded PEGDA-AA hydrogel coatings for inhibition of titanium implants associated infections

Ciprofloxacin-modified electrosynthesized hydrogel coatings to prevent titanium-implant-associated infections

New promising and versatile materials for the development of in situ sustained release systems consisting of thin films of either poly(2-hydroxyethyl methacrylate) or a copolymer based on poly(ethylene-glycol diacrylate) and acrylic acid were investigated. These polymers were electrosynthesized directly on titanium substrates and loaded with ciprofloxacin (CIP) either during or after the synthesis step. X-ray photoelectron spectroscopy was used to check the CIP entrapment efficiency as well as its surface availability in the hydrogel films, while high-performance liquid chromatography was employed to assess the release property of the films and to quantify the amount of CIP released by the coatings. These systems were then tested to evaluate the in vitro inhibition of methicillin-resistant Staphylococcus aureus (MRSA) growth. Moreover, a model equation is proposed which can easily correlate the diameter of the inhibition haloes with the amount of antibiotic released. Finally, MG63 human osteoblast-like cells were employed to assess the biocompatibility of CIP-modified hydrogel coatings.

Biocompatibility of Poly(Acrylic Acid) Thin Coatings Electro-synthesized onto TiAlV-based Implants

The protection of metal orthopedic implants against corrosion is a crucial medical problem. It was found that electrochemical polymerization of thin, passive poly(acrylic acid) (PAA) films on titanium and TiAlV substrates provides good anti-corrosion properties. In this work, an investigation of anti-corrosion features was carried out to clarify the hypothesis of the presence of an electrostatic contribution to the performance of a PAA coating. Ion release tests were performed at three different pHs; the pH dependence of the polymer swelling was examined by quartz crystal microbalance with dissipation monitoring, to establish the role of this phenomenon on the polymer barrier properties. The potential application of these PAA thin films as biocompatible protective coatings for metal implants and compatibility towards MG-63 human osteoblast-like cells was assessed.

Development and characterization of rhVEGF-loaded poly(HEMA-MOEP) coatings electrosynthesized on titanium to enhance bone mineralization and angiogenesis.

Osteointegration of titanium implants could be significantly improved by coatings capable of promoting both mineralization and angiogenesis. In the present study, a copolymeric hydrogel coating, poly-2-hydroxyethyl methacrylate-2-methacryloyloxyethyl phosphate (P(HEMA-MOEP)), devised to enhance calcification in body fluids and to entrap and release growth factors, was electrosynthesized for the first time on titanium substrates and compared to poly-2-hydroxyethyl methacrylate (PHEMA), used as a blank reference. Polymers exhibiting negatively charged groups, such as P(HEMA-MOEP), help to enhance implant calcification. The electrosynthesized coatings were characterized by X-ray photoelectron spectroscopy and atomic force microscopy. MG-63 human osteoblast-like cell behaviour on the coated specimens was investigated by scanning electron microscopy, MTT viability test and osteocalcin mRNA detection. The ability of negatively charged phosphate groups to promote hydroxyapatite-like calcium phosphate deposition on the implants was explored by immersing them in simulated body fluid. Similar biological responses were observed in both coated specimens, while calcium-phosphorus globules were detected only on P(HEMA-MOEP) surfaces pretreated with alkaline solution. Testing of the ability of P(HEMA-MOEP) hydrogels to entrap and release human recombinant vascular endothelial growth factor, to tackle the problem of insufficient oxygen and nutrient delivery, suggested that P(HEMA-MOEP)-coated titanium prostheses could represent a multifunctional material suitable for bone restoration applications.

PHEMA-based thin hydrogel films for biomedical applications

Poly(2-hydroxyethyl methacrylate) based thin coatings were electro-synthesized by cyclic voltammetry on Au-coated quartz crystal surfaces to study different solid—liquid interfacial processes. By varying the electrochemical parameters and the presence or not of a crosslinking agent, films were obtained with thicknesses ranging from 5 to 90 nm. Surface characterization was performed by X-ray photoelectron spectroscopy, atomic force microscopy, and static contact angle measurements. Using quartz crystal microbalance with dissipation monitoring to investigate the relationship between the film thickness and the swelling behavior, it was found that these characteristics can be modulated by varying either the number of voltammetric cycles or the presence of the crosslinker. Cell adhesion and biocompatibility tests indicate that these film coatings were suitable for biomedical applications.

Microcantilevers and organic transistors: two promising classes of label-free biosensing devices which can be integrated in electronic circuits

AbstractMost of the success of electronic devices fabricated to actively interact with a biological environment relies on the proper choice of materials and efficient engineering of surfaces and interfaces. Organic materials have proved to be among the best candidates for this aim owing to many properties, such as the synthesis tunability, processing, softness and self-assembling ability, which allow them to form surfaces that are compatible with biological tissues. This review reports some research results obtained in the development of devices which exploit organic materials’ properties in order to detect biologically significant molecules as well as to trigger/capture signals from the biological environment. Among the many investigated sensing devices, organic field-effect transistors (OFETs), organic electrochemical transistors (OECTs) and microcantilevers (MCLs) have been chosen. The main factors motivating this choice are their label-free detection approach, which is particularly important when addressing complex biological processes, as well as the possibility to integrate them in an electronic circuit. Particular attention is paid to the design and realization of biocompatible surfaces which can be employed in the recognition of pertinent molecules as well as to the research of new materials, both natural and inspired by nature, as a first approach to environmentally friendly electronics. FigureRepresentative scheme of biorecognition in Organic Transistor and Microcantilever devices

Membrane proteins embedded in supported lipid bilayers employed in field effect electronic devices

A novel bottom-gate top-contact OTFT architecture has been fabricated. In this device, a lipid bilayer structure embedding a photosynthetic membrane protein extracted from Rhodobacter Sphaeroides has been deposited onto the organic semiconductor film (α,ω-dihexylsexythiophene) prior to the evaporation of source and drain gold contacts. The figures of merit of this device were extracted and compared to those obtained for the same OTFT devoid of the biological film. Only slightly lower performances in terms of field-effect mobility (µ) were observed for the lipid bilayer OTFT that exhibits µ=0.007 cm2/Vs. This result constitutes a preliminary important starting point towards the development of novel highly sensitive and selective herbicides sensors.