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We report on a comparative in vitro study of selective cytotoxicity against MCF7 tumor cells and normal VERO cells tested on silver-based nanocoatings synthesized by the matrix-assisted pulsed laser evaporation (MAPLE) technique. Silver nanoparticles (AgNPs) were loaded with five representative cytostatic drugs (i.e., doxorubicin, fludarabine, paclitaxel, gemcitabine, and carboplatin) and with five essential oils (EOs) (i.e., oregano, rosemary, ginger, basil, and thyme). The as-obtained coatings were characterized by X-ray diffraction, thermogravimetry coupled with differential scanning calorimetry, Fourier-transform IR spectroscopy, IR mapping, and scanning electron microscopy. A screening of the impact of the prepared nanocoatings on the MCF7 tumor and normal VERO cell lines was achieved by means of cell viability MTT and cytotoxicity LDH assays. While all nanocoatings loaded with antitumor drugs exhibited powerful cytotoxic activity against both the tumor and the normal cells, those embedded with AgNPs loaded with rosemary and thyme EOs showed remarkable and statistically significant selective cytotoxicity against the tested cancercells. The EO-loaded nanocoatings were tested for antimicrobial and antibiofilm activity against Staphylococcus aureus, Escherichia coli, and Candida albicans. For all studied pathogens, the cell viability, assessed by counting the colony-forming units after 2 and 24 h, was significantly decreased by all EO-based nanocoatings, while the best antibiofilm activity was evidenced by the nanocoatings containing ginger and thyme EOs.

The second part of our review describing new achievements in the field of biofilm prevention and control, begins with a discussion of the active antibiofilm nanocoatings. We present the antibiofilm strategies based on antimicrobial agents that kill pathogens, inhibit their growth, or disrupt the molecular mechanisms of biofilm-associated increase in resistance and tolerance. These agents of various chemical structures act through a plethora of mechanisms targeting vital bacterial metabolic pathways or cellular structures like cell walls and cell membranes or interfering with the processes that underlie different stages of the biofilm life cycle. We illustrate the latter action mechanisms through inhibitors of the quorum sensing signaling pathway, inhibitors of cyclic-di-GMP signaling system, inhibitors of (p)ppGpp regulated stringent response, and disruptors of the biofilm extracellular polymeric substances matrix (EPS). Both main types of active antibiofilm surfaces, namely non-leaching or contact killing systems, which rely on the covalent immobilization of the antimicrobial agent on the surface of the coatings and drug-releasing systems in which the antimicrobial agent is physically entrapped in the bulk of the coatings, are presented, highlighting the advantages of each coating type in terms of antibacterial efficacy, biocompatibility, selective toxicity, as well as drawbacks and limitations. Developments regarding combined strategies that join in a unique platform, both passive and active elements are not omitted. In such platforms with dual functionality, passive and active strategies can be applied either simultaneously or sequentially. We especially emphasize those systems that can be reversely and repeatedly switched between the non-fouling status and the bacterial killing status, thereby allowing several bacteria-killing/surface regeneration cycles to be performed without significant loss of the initial bactericidal activity. Eventually, smart antibiofilm coatings that release their antimicrobial payload on demand, being activated by various triggers such as changes in local pH, temperature, or enzymatic triggers, are presented. Special emphasis is given to the most recent trend in the field of anti-infective surfaces, specifically smart self-defensive surfaces for which activation and switch to the bactericidal status are triggered by the pathogens themselves.

Globally, cancer is the second most common cause of death, and Europe accounts for almost 25% of the global cancer burden, although its people make up only 10% of the world’s population. Conventional systemically administered anti-cancer drugs come with important drawbacks such as inefficiency due to poor bioavailability and improper biodistribution, severe side effects associated with low therapeutic indices, and the development of multidrug resistance. Therefore, smart nano-engineered targeted drug-delivery systems with tailored pharmacokinetics and biodistribution which can selectively deliver anti-cancer agents directly to the tumor site are the solution to most difficulties encountered with conventional therapeutic tools. Here, we report on the synthesis, physicochemical characterization, and in vitro evaluation of biocompatibility and anti-tumor activity of novel magnetically targetable SPIONs based on magnetite (Fe3O4) nanoparticles’ surface modified with β-cyclodextrin (CD) and paclitaxel (PTX)–guest–host inclusion complexes (Fe3O4@β-CD/PTX). Both pristine Fe3O4@β-CD nanopowders and PTX-loaded thin films fabricated by MAPLE technique were investigated. Pristine Fe3O4@β-CD and Fe3O4@β-CD/PTX thin films were physicochemically characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The biocompatibility of bare magnetic nanocomposite thin films was evaluated by MTT cell viability assay on a normal 3T3 osteoblast cell line culture and by measuring the level of NO in the culture medium. No significant modifications, neither in cell viability nor in NO level, could be observed, thereby demonstrating the excellent biocompatibility of the SPIONs thin films. Inverted phase-contrast microscopy showed no evident adverse effect on the morphology of normal osteoblasts. On the other hand, Fe3O4@β-CD/PTX films decreased the cell viability of the MG-63 osteosarcoma cell line by 85%, demonstrating excellent anti-tumor activity. The obtained results recommend these magnetic hybrid films as promising candidates for future delivery, and hyperthermia applications in cancer treatment.

This work reports the non-surfactant templated synthesis and characterization of a new tyrosine—silica/antibiotics (TyR-SiO2/ATBs) nanocomposite, as well as both in vitro and in vivo cytotoxicity and antimicrobial activity against the microbial pathogen Staphylococcus aureus. The in vitro microbiological tests proved that the obtained nanobiostructure significantly enhance the antimicrobial activity of three commonly used antibiotics against S. aureus (i.e. erythromycin (ERI), gentamicin (GEN), and cloxacillin (CLO)) as revealed by the increased diameters of the growth inhibition zones and the decreased minimal inhibitory concentration values, as well as by the inhibitory effect of sub-lethal antibiotic concentrations on the ability of the respective pathogenic strains to adhere and colonize different substrata. These results, correlated with the lack of toxicity against mesenchymal stem cells along with an appropriate in vivo biodistribution highlight the promising therapeutic potential of this carrier that allows a decrease of the required active doses while significantly lessening the harmful side effects of the medication on the host organism.

In this study, we investigated the potential of MAPLE-deposited coatings mesoporous silica nanoparticles (MSNs) to release Zinforo (ceftarolinum fosmil) in biologically active form. The MSNs were prepared by using a classic procedure with cetyltrimethylammonium bromide as sacrificial template and tetraethylorthosilicate as the monomer. The Brunauer–Emmett–Teller (BET) and transmission electron microscopy (TEM) analyses revealed network-forming granules with diameters under 100 nm and an average pore diameter of 2.33 nm. The deposited films were characterized by SEM, TEM, XRD and IR. Microbiological analyses performed on ceftaroline-loaded films demonstrated that the antibiotic was released in an active form, decreasing the microbial adherence rate and colonization of the surface. Moreover, the in vitro and in vivo assays proved the excellent biodistribution and biocompatibility of the prepared systems. Our results suggest that the obtained bioactive coatings possess a significant potential for the design of drug delivery systems and antibacterial medical-use surfaces, with great applications in bone implantology.

The paper reports the synthesis and physico-chemical and biological characterization of novel wound dressings based on collagen and essential oil functionalized ZnO nanoparticles intended to improve the treatment of burns and to reduce the risk for developing wound sepsis in patients with burns or chronic wounds. The prepared wound dressings were physico-chemical characterized by Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). In vitro biocompatibility and cytotoxicity was proved on human fibroblast cells, antimicrobial potential was assessed on Gram positive and Gram negative bacteria models (Staphylococcus aureus and Escherichia coli, respectively), while in vivo studies were performed on a rat burn wound experimental model. Functionalized ZnO nanoparticles (NPs) proved to range 15–20 nm in size and contain about 1% orange essential oil (EO), which was utilized as a natural antimicrobial agent. NPs are grain-shapped and have a low tendency to form aggregates. No toxicity was noticed in vitro, as human fibroblasts maintained a normal growth and their membrane integrity in the presence of EO functionalized NPs. The capacity of the prepared wound dressings to act as implantable bioresorbable scaffolds that accelerates wounds healing along with an excellent biocompatibility, lack of cytotoxicity and a good antibacterial activity, make these materials promising and safe candidates for wound dressing, especially in burn patients.

The increasing rate of antibiotic resistant bacteria associated with nosocomial infections in severely ill patients has urged the need for new antibacterial therapies. Nanostructured materials represent emerging innovative approaches to controlled delivery of different antimicrobial drugs. Delivery systems encapsulating natural compounds with antibacterial effects, such as essential oils have shown a great potential. Herein we report the development of SiO2 mesoporous nanosystems loaded with eucalyptus (EUC), orange (ORA), and cinnamon (CIN) essential oils. These systems were characterized with respect to morphology (using scanning electron microscopy, SEM, and transmission electron microscopy, TEM), porosity (by BET and TEM analysis), chemical composition (by X-ray diffraction, XRD, and Fourier transform infrared spectrometry, FTIR) and loading capacity (by thermogravimetric analysis, TGA). The anti-bacterial and anti-adherence effects were tested against clinically relevant microbial species (Staphylococcus aureus ATCC 25923; Escherichia coli ATCC 25922; and Candida albicans ATCC 10231), while the biocompatibility was evaluated by in vitro tests with L929 mouse fibroblast cells.

Heavy metal ions contamination resulting mainly from various industrial activities, mining, agricultural, and transportation, but also from domestic activities and from natural sources is a serious problem of our days, leading to an ever-increasing concern about the safety and accessibility of drinking water. In some developing countries permanent supply with fresh water can be a challenge that the population in those areas has to face every day. Worldwide there are about 780 million people who lack access to improved drinking-water sources. Arsenic groundwater contamination in the delta of the Ganges that covers a vast area comprising Bangladesh and the state of West Bengal, India is a major calamity of our days. Due to their unique physicochemical and surface properties, nanomaterials could provide some revolutionary solutions to the global problem of ensuring the ever-increasing world population with safe drinking water under the conditions of diversification and multiplication of water contamination sources. Some solutions involve “carbonaceous” materials, such as carbon nanotubes, graphene oxide, nanostructured carbon, others involving metal oxides, magnetic metal oxides, natural polymers, waste materials, and others. Some studies even come up with integrated solutions, taking them from the laboratory scale to industrial applications. However, the need for a better characterization and for a higher rate of application of the solutions that are being proposed still remains.

According to the Food and Agricultural Organization of the United Nations (FAO) there are 795 million undernourished people in the world, 780 million of them leaving in the developing countries. The average rate of crop losses caused by pests (weeds, insects, rodents, and diseases) lies between 20% and 40% depending on the type of the crop and on the geographic region and it exceeds 50% in the developing countries of Central Africa. Conventional pesticides exhibit a series of major drawbacks that severely limited the use of these chemical pest control agents over the past few decades, the most important ones being the harmful effect on nontarget organisms, the persistence in the environment, the biomagnification in organisms that are higher up in the food chain, and the emergence of resistant populations of target organisms. The present chapter describes how it possible to overcome these drawbacks by using nanopesticide delivery systems. Nanopesticides are classified and described taking the chemical composition of the nanocarrier (organic polymer-based formulations, lipid-based formulations, nanosized metals, and metal oxides, clay based nanomaterials, layered double hydroxides, silica nanoparticles) into account. Furthermore, within each of the aforementioned classes, nanovehicles are presented according to the structural and morphological characteristics individualizing each type of nanocarrier (nanocapsules, nanospheres, micelles, nanogels, nanofibers, nanoliposomes, solid lipid nanoparticles, nanoemulsions, microemulsions, nanodispersions). Throughout the chapter, the most significant achievements in the field are illustrated by carefully selected up-to-date examples, in each case highlighting the superior performances of nanopesticides relative to their bulk counterparts in terms of selectivity, efficiency, and reduction of the harmful environmental impact.

Development of antibiotic-resistant bacterial strains is becoming a worldwide public health problem. Each year several million people acquire infections from antibiotic-resistant bacteria and at least 25,000 die each year in the European Union as a direct consequence of these infections. Many more die as a result of other conditions complicated by these infections. Therefore solving this crisis requires new effective weapons to fight against antibiotic-resistant bacteria. Nanoantibiotics encompassing both nanoplatforms for antibiotic delivery and nanomaterials exhibiting intrinsic antimicrobial properties appear as a very promising solution. Smart programmed nano drug delivery systems can perform both the selective targeted transport of the antibiotic to the infected sites and “on demand” release of the antibiotic resulting in controlled biodistribution and significantly improved pharmacokinetics. Moreover, nano drug delivery systems (nanoDDS) can be engineered so that they effectively bypass drug resistance mechanisms. This chapter deals with nanoantibiotics based on synthetic or natural biocompatible and biodegradable polymeric materials. The polymer molecular architectures most relevant to drug delivery applications are presented along with the controlled polymerization methods allowing their synthesis. The main methods used for the preparation of antibiotic-loaded nanoparticles including emulsion polymerization, interfacial polymerization, nanoprecipitation, emulsion-solvent diffusion, emulsion-solvent evaporation, salting out, dialysis, electrospinning, and electrospraying are illustrated by relevant carefully selected examples from the literature. Antimicrobial synthetic and natural polymers, antibiotic-polymer conjugates, and supramolecular nanoplatforms based on organic polymers for smart delivery of antibiotics are presented, highlighting the advantages they provide, with special emphasis on their selectivity and antimicrobial performances. Throughout the chapter the most significant achievements along with the newest reports in the field are provided.

The aim of this study was to obtain a nano-active system to improve antibiotic activity of certain drugs by controlling their release. Magnetic composite nanomaterials based on magnetite core and cross-linked chitosan shell were synthesized via the co-precipitation method and characterized by Fourier transform infrared spectroscopy (FT-IR), infrared microscopy (IRM), scanning electron microscopy (SEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The prepared magnetic composite nanomaterials exhibit a significant potentiating effect on the activity of two cationic (kanamycin and neomycin) drugs, reducing the amount of antibiotics necessary for the antimicrobial effect. The increase in the antimicrobial activity was explained by the fact that the obtained nanosystems provide higher surface area to volume ratio, resulting into higher surface charge density thus increasing affinity to microbial cell and also by controlling their release. In addition to the nano-effect, the positive zeta potential of the synthesized magnetite/cross-linked chitosan core/shell magnetic nanoparticles allows for a more favorable interaction with the usually negatively charged cell wall of bacteria. The novelty of the present contribution is just the revealing of this synergistic effect exhibited by the synthesized water dispersible magnetic nanocomposites on the activity of different antibiotics against Gram-positive and Gram-negative bacterial strains. The results obtained in this study recommend these magnetic water dispersible nanocomposite materials for applications in the prevention and treatment of infectious diseases.

New electrochemical sensors for dopamine (DA) and phenol derivative, based on hybrid inorganic redox material-organic conducting polymers, were developed. Hybrid inorganic–organic coatings based on Prussian blue, polyazulene, poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(3-[(E)-2-azulene-1-yl)vinyl]thiophene) have been prepared by electrochemical methods in various configurations onto Pt substrate. Dopamine and 4-nitrophenol (4-NP) have been determined by square wave voltammetry using both mono and bilayer modified electrodes. The modified electrodes exhibited a linear response over wide range of 4-nitrophenol concentrations from 30 to 90 μM, with a detection limit of 8.23 μM (s/n = 3). A linear trend for the responses for dopamine concentrations ranging from 2 to 100 μM, with a sensitivity of 0.116 μA/μM, has been also obtained.

Background Smart triggered release in controlled drug delivery has met an astonishing interest from the scientific community in the past few years due to the obvious medical benefits this type of systems represents. The reduction in toxicity due to a non-systemic administration is not the only reason for this increase, although it is a major reason for concern typically in anti-cancer therapy, but also the fact that some good therapeutic substances cannot be used either due to their high hydrophobicity or due to a very poor absorption at the required site of delivery. Objective This review article aims to highlight the efforts made by the scientific community in order to more efficiently trigger the drug payload at its destination, thus avoiding systemic exposure to the drug's toxic effect. Results In this review article several types of triggers have been evaluated, pH triggered delivery, thermally triggered delivery, REDOX change triggered delivery, as well as modifications made to trigger at a specific location based on the affinity of the receptors for a certain chemical moiety, such as folic acid. Conclusions Through a proper nano-formulation the obstacles encountered by systemic delivery strategies can be circumvented, and through minor modifications hydrophobic drugs can be delivered through minor modifications to their structure, ensuring in the meantime that the therapeutic form is broken down by the human body's own internal systems. The main advantages in triggered drug delivery are the better healthcare strategy and the topical delivery, the main person winning in this case being the patient, the one person that should always be at the heart of the medical system.

The article is an up-to-date review of the state-of-the art in the challenging field of smart synthetic polymer nanocarriers, presenting the most relevant achievements in the area, with a special emphasis on the outstanding potential of these nanovehicles to be used as multifunctional devices capable to deliver their cargo to a specific targeted area in the human body and to release it in a well controlled fashion. Stimuli-responsive nano drug delivery systems are presented according to a classification that takes into account the endogenous or exogenous nature of the stimuli. Each category is amply illustrated by carefully selected examples of the most impressive achievements. The endogenous stimuli category is fully described by presentation of pH, redox potential, and enzyme-responsive nanocarriers. From the category of exogenous stimuli-responsive nanomaterials, we focused our attention on temperature, light and magnetic sensitive nanocarriers.

Smart multifunctional polymeric nanocarriers able to respond to physicochemical changes in their environment or to external stimuli represent a new paradigm in the field of pharmaceutical formulations for controlled drug delivery. The introductory part of the present review deals with this new concept and presents the main advantages resulting from the use of such nanovehicles instead of conventional, much larger drug delivery systems. The access to drug nanocarriers based on smart supramolecular polymeric materials is primarily limited by the available polymerization methods capable to produce polymers with low polydispersity index, as well as much more complex macromolecular architectures with strictly controlled chemical composition, such as block copolymers and star or graft polymers or copolymers. This article reviews the state-of-the art in controlled/"living" free radical polymerization techniques as well as ring opening polymerization methods. Nitroxide mediated free radical polymerization (NMP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain-transfer polymerization (RAFT), single electron transfer-living radical polymerization (SET-LRP), single electron transfer-nitroxide radical coupling reaction (SET-NRC), cationic ring opening polymerization (CROP), anionic ring opening polymerization (AROP), and metal catalyzed ring opening polymerization are described, highlighting their mechanistic details and their synthetic potential as well as their limitations. The final part of the article is dedicated to a special type of unimolecular, monodisperse nanocarriers - the dendrimers. Both divergent and convergent approaches to dendrimer synthesis are described along with the therapeutic applications taking advantage of the unique branched tree-like globular structure of dendrimers to treat cancer.

International audience; Bio-composite coatings consisting of poly(3,4-ethylenedioxythiophene) (PEDOT) and tyrosinase (Ty) were successfully electrodeposited on conventional size gold (Au) disk electrodes and microelectrode arrays using sinusoidal voltages. Electrochemical polymerization of the corresponding monomer was carried out in the presence of various Ty amounts in aqueous buffered solutions. The bio-composite coatings prepared using sinusoidal voltages and potentiostatic electrodeposition methods were compared in terms of morphology, electrochemical properties, and biocatalytic activity towards various analytes. The amperometric biosensors were tested in dopamine (DA) and catechol (CT) electroanalysis in aqueous buffered solutions. The analytical performance of the developed biosensors was investigated in terms of linear response range, detection limit, sensitivity, and repeatability. A semi-quantitative multi-analyte procedure for simultaneous determination of DA and CT was developed. The amperometric biosensor prepared using sinusoidal voltages showed much better analytical performance. The Au disk biosensor obtained by 50 mV alternating voltage amplitude displayed a linear response for DA concentrations ranging from 10 to 300 μM, with a detection limit of 4.18 μM

Functionalized magnetic nanoparticles followed two main directions in the field of biomedical applications: one direction is as image enhancing agents for magnetic resonance imaging (MRI) and the other is as drugdelivery devices for various biologically-active substances. A third field which just emerges in nanomedicine is the field of the so-called theranostic devices which combines in the same delivery vehicle both the therapeutic agent and the contrast substance. The advantages of using nanoparticles instead of larger carriers for delivery of both drug and image contrast enhancing agents will be highlighted throughout this review article. Despite the ever increasing number of articles reporting both in vitro and in vivo studies carried out on functionalized magnetic nanoparticles and envisaging their potential biomedical applications, only few formulations reached the phase of clinical trials and even fewer became marketed products. The perspectives in the field are open, since new drugs require new delivery devices and possibly new means of functionalization. At the same time, the field of nanomedicine also provides the opportunity to better exploit drugs that are already in clinical use by improving their bioavailability through appropriate nanoformulations.