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The paper aims to investigate the antitumor activity of a series of phenothiazine derivatives in order to establish a structure–antitumor activity relationship. To this end, PEGylated and TEGylated phenothiazine have been functionalized with formyl units and further with sulfonamide units via dynamic imine bonds. Their antitumor activity was monitored in vitro against seven human tumors cell lines and a mouse one compared to a human normal cell line by MTS assay. In order to find the potential influence of different building blocks on antitumor activity, the antioxidant activity, the ability to inhibit farnesyltransferase and the capacity to bind amino acids relevant for tumor cell growth were investigated as well. It was established that different building blocks conferred different functionalities, inducing specific antitumor activity against the tumor cells. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate the ability of a solid-state material, prepared by crosslinking chitosan with a phenothiazine-based aldehyde, to remove copper (II) ions from aqueous solutions, in a fast and selective manner. The metal uptake experiments, including the retention, sensibility, and selectivity against eight different metal ions, were realized via batch adsorption studies. The capacity of the material to retain copper (II) ions was investigated by spectrophotometric measurements, using poly(ethyleneimine) complexation agent, which allowed detection in a concentration range of 5–500 µM. The forces driving the copper sorption were monitored using various methods, such as FTIR spectroscopy, X-ray diffraction, SEM-EDAX technique, and optical polarized microscopy, and the adsorption kinetics were assessed by fitting the in vitro sorption data on different mathematical models. The phenothiazine-imine-chitosan material proved high ability to recover copper from aqueous media, reaching a maximum retention capacity of 4.394 g Cu (II)/g adsorbent when using a 0.5 M copper solution, which is an outstanding value compared to other chitosan-based materials reported in the literature to this date. It was concluded that the high ability of the studied xerogel to retain Cu (II) ions was the result of both physio- and chemo-sorption processes. This particular behavior was favored on one hand by the porous nature of the material and on the other hand by the presence of amine, hydroxyl, imine, and amide groups with the role of copper ligands. [ABSTRACT FROM AUTHOR]

A mixture of polymeric complexes based on the reaction between Re(CO)5Cl and the porous polymeric network coming from the coupling of melamine and benzene-1,3,5-tricarboxaldehyde was obtained and characterized by FTIR, NMR, SEM, XPS, ICP, XRD, and cyclic voltammetry (CV). The formed rhenium-based porous hybrid material reveals a noticeable capability of CO2 absorption. The gas absorption amount measured at 295 K was close to 44 cm3/g at 1 atm. An interesting catalytic activity for CO2 reduction reaction (CO2RR) is observed, resulting in a turn over-number (TON) close to 6.3 under 80 min of test at −1.8 V vs. Ag/AgCl in a TBAPF6 0.1 M ACN solution. A possible use as filler in membranes or columns can be envisaged. [ABSTRACT FROM AUTHOR]

This paper reports new solid materials based on TEGylated phenothiazine and chitosan, with a high capacity to recover mercury ions from aqueous solutions. They were prepared by hydrogelation of chitosan with a formyl derivative of TEGylated phenothiazine, followed by lyophilization. Their structural and supramolecular characterization was carried out by 1H-NMR and FTIR spectroscopy, as well as X-ray diffraction and polarized light microscopy. Their morphology was investigated by scanning electron microscopy and their photophysical behaviour was examined by UV/Vis and emission spectroscopy. Swelling evaluation in different aqueous media indicated the key role played by the supramolecular organization for their hydrolytic stability. Mercury recovery experiments and the analysis of the resulting materials by X-ray diffraction and FTIR spectroscopy showed a high ability of the studied materials to bind mercury ions by coordination with the sulfur atom of phenothiazine, imine linkage, and amine units of chitosan. [ABSTRACT FROM AUTHOR]

Erythromycin (ERY) is a macrolide compound with a broad antimicrobial spectrum which is currently being used to treat a large number of bacterial infections affecting the skin, respiratory tract, intestines, bones and other systems, proving great value from a clinical point of view. It became popular immediately after its discovery in 1952, due to its therapeutic effect against pathogens resistant to other drugs. Despite this major advantage, ERY exhibits several drawbacks, raising serious clinical challenges. Among them, the very low solubility in water and instability under acidic conditions cause a limited efficacy and bioavailability. Apart from this, higher doses promote drug resistance and undesirable effects. In order to overcome these disadvantages, during the past decades, a large variety of ERY formulations, including nanoparticles, have emerged. Despite the interest in ERY-(nano)formulations, a review on them is lacking. Therefore, this work was aimed at reviewing all efforts made to encapsulate ERY in formulations of various chemical compositions, sizes and morphologies. In addition, their preparation/synthesis, physico-chemical properties and performances were carefully analysed. Limitations of these studies, particularly the quantification of ERY, are discussed as well. [ABSTRACT FROM AUTHOR]

The paper aims at the preparation of chitosan self-healing hydrogels, designed as carriers for local drug delivery by parenteral administration. To this aim, 30 hydrogels were prepared using chitosan and pyridoxal 5-phosphate (P5P), the active form of vitamin B6 as precursors, by varying the ratio of glucosamine units and aldehyde on the one hand and the water content on the other hand. The driving forces of hydrogelation were investigated by nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction, and polarized light microscopy (POM) measurements. NMR technique was also used to investigate the stability of hydrogels over time, and their morphological particularities were assessed by scanning electron microscopy (SEM). Degradability of the hydrogels was studied in media of four different pH, and preliminary self-healing ability was visually established by injection through a syringe needle. In-depth rheological investigation was conducted in order to monitor the storage and loss moduli, linear viscoelastic regime, and structural recovery capacity. It was concluded that chitosan crosslinking with pyridoxal 5-phosphate is a suitable route to reach self-healing hydrogels with a good balance of mechanical properties/structural recovery, good stability over time, and degradability controlled by pH. [ABSTRACT FROM AUTHOR]

A series of drug delivery systems were prepared by chitosan hydrogelation with citral in the presence of an antineoplastic drug: 5-fluorouracil. The dynamic covalent chemistry of the imine linkage allowed the obtaining of supramolecular tridimensional architectures in which the drug has been homogenously dispersed. Fourier-transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WXRD) and polarized light microscopy (POM) measurements were used in order to follow the hydrogelation and drug encapsulation processes. The ability of the prepared systems to release the drug has been investigated by UV-Vis spectroscopy using a calibration curve and by fitting the results with different mathematic models. To mimic the behavior of the hydrogel matrix in bio-environmental conditions in view of applications, their enzymatic degradability was monitored in the presence of lysozyme. The in vivo side effects of the systems, in terms of their influence on the blood elements, biochemical and immune parameters were monitored on white Swiss mice by intraperitoneal administration of the injectable obtained hydrogels. All the characteristics of the obtained systems, such as micro-porous morphology, uniform drug encapsulation, enzymatic degradability, lack of side effects, other than the one of the drug itself, along with their ability to release the drug in a sustained manner proved that these material meet the requirements for the development of drug delivery systems, making them suitable for being applied in intraperitoneal chemotherapy. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a lethal brain cancer with a very difficult therapeutic approach and ultimately frustrating results. Currently, therapeutic success is mainly limited by the high degree of genetic and phenotypic heterogeneity, the blood brain barrier (BBB), as well as increased drug resistance. Temozolomide (TMZ), a monofunctional alkylating agent, is the first line chemotherapeutic drug for GBM treatment. Yet, the therapeutic efficacy of TMZ suffers from its inability to cross the BBB and very short half-life (~2 h), which requires high doses of this drug for a proper therapeutic effect. Encapsulation in a (nano)carrier is a promising strategy to effectively improve the therapeutic effect of TMZ against GBM. Although research on liposomes as carriers for therapeutic agents is still at an early stage, their integration in GBM treatment has a great potential to advance understanding and treating this disease. In this review, we provide a critical discussion on the preparation methods and physico-chemical properties of liposomes, with a particular emphasis on TMZ-liposomal formulations targeting GBM developed within the last decade. Furthermore, an overview on liposome-based formulations applied to translational oncology and clinical trials formulations in GBM treatment is provided. We emphasize that despite many years of intense research, more careful investigations are still needed to solve the main issues related to the manufacture of reproducible liposomal TMZ formulations for guaranteed translation to the market. [ABSTRACT FROM AUTHOR]

Microporous chitosan nanofibers functionalized with different amounts of an antimicrobial agent via imine linkage were prepared by a three-step procedure including the electrospinning of a chitosan/PEO blend, PEO removal and acid condensation reaction in a heterogeneous system with 2-formylphenylboronic acid. The fibers' characterization was undertaken keeping in mind their application to wound healing. Thus, by FTIR and 1H-NMR spectroscopy, it was confirmed the successful imination of the fibers and the conversion degree of the amine groups of chitosan into imine units. The fiber morphology in terms of fiber diameter, crystallinity, inter- and intra-fiber porosity and strength of intermolecular forces was investigated using scanning electron microscopy, polarized light microscopy, water vapor sorption and thermogravimetric analysis. The swelling ability was estimated in water and phosphate buffer by calculating the mass equilibrium swelling. The fiber biodegradation was explored in five media of different pH, corresponding to different stages of wound healing and the antimicrobial activity against the opportunistic pathogens inflicting wound infection was investigated according to standard tests. The biocompatibility and bioadhesivity were studied on normal human dermal fibroblast cells by direct contact procedure. The dynamic character of the imine linkage of the functionalized fibers was monitored by UV-vis spectroscopy. The results showed that the functionalization of the chitosan microporous nanofibers with antimicrobial agents via imine linkage is a great route towards bio-absorbable wound dressings with "on demand" antimicrobial properties and biodegradation rate matching the healing stages. [ABSTRACT FROM AUTHOR]

Here, we report a non-toxic method for improving the oil-resistant performance of chitosan coated paper by coating the mixture of chitosan and montmorillonite (MMT) instead of coating chitosan solution only. Through combining MMT into the chitosan coatings, the coated paper exhibited a lower air permeability and enhanced oil resistance under a lower coating load. For coated papers C2.5 and C3 by coating 2.5% (w/v) and 3% (w/v) chitosan without adding MMT in the chitosan coating, the coating load was 3.76 g/m2 and 3.99 g/m2, respectively, and the kit rating values were only 7–8/12. Regarding the sample C2M0.1 coated by the mixed solution containing 2% (w/v) chitosan and 0.1% (w/v) MMT, its coating load was only 3.65 g/m2, the paper permeability after coating was reduced to 0.00507 μm/Pa·s, owing to the filling of MMT into the cellulosic fibers network, and the kit rating reached 9/12. Moreover, C2M0.1 showed improved mechanical properties, whereby its tearing resistance was 5.2% and 6.6% higher than that of the uncoated paper in the machine direction and the cross direction, respectively. [ABSTRACT FROM AUTHOR]

Herein, the effect of three deterpenated fractions from Origanum majorana L. essential oil on the physicochemical, mechanical and biological properties of chitosan/β-chitin nanofibers-based nanocomposite films were investigated. In general, the incorporation of Origanum majorana L. original essential oil or its deterpenated fractions increases the opacity of the nanocomposite films and gives them a yellowish color. The water solubility decreases from 58% for chitosan/β-chitin nanofibers nanocomposite film to around 32% for the nanocomposite films modified with original essential oil or its deterpenated fractions. Regarding the thermal stability, no major changes were observed, and the mechanical properties decreased. Interestingly, data show differences on the biological properties of the materials depending on the incorporated deterpenated fraction of Origanum majorana L. essential oil. The nanocomposite films prepared with the deterpenated fractions with a high concentration of oxygenated terpene derivatives show the best antifungal activity against Aspergillus niger, with fungal growth inhibition of around 85.90%. Nonetheless, the only nanocomposite film that does not present cytotoxicity on the viability of L929 fibroblast cells after 48 and 72 h is the one prepared with the fraction presenting the higher terpenic hydrocarbon content (87.92%). These results suggest that the composition of the deterpenated fraction plays an important role in determining the biological properties of the nanocomposite films. [ABSTRACT FROM AUTHOR]

A series of new azomethine dimers was synthesized by the condensation reaction of flexible bis-benzaldehydes with four aromatic amines containing phenyl, naphthyl, anthracene and pyrene groups. Their right structure was confirmed by FTIR and 1H-NMR spectroscopy and their thermal properties were investigated by thermogravimetric analysis, differential scanning calorimetry and polarized light optical microscopy. A view on their photophysical behavior was gained by UV-vis and photoluminescence spectroscopy. The dimers containing pyrene and anthracene presented liquid crystalline behavior, while the other dimers were crystalline compounds. Two dimers containing pyrene moieties formed mesomorphic glasses and had intense luminescence, promising properties for applications in building optoelectronic devices. [ABSTRACT FROM AUTHOR]

The aim of the study was to create a mathematical model useful for monitoring the release of bioactive aldehydes covalently bonded to the chitosan by reversible imine linkage, considered as a polymer–drug system. For this purpose, two hydrogels were prepared by the acid condensation reaction of chitosan with the antifungal 2-formyl-phenyl-boronic acid and their particularities; influencing the release of the antifungal aldehyde by shifting the imination equilibrium to the reagents was considered, i.e., the supramolecular nature of the hydrogels was highlighted by polarized light microscopy, while scanning electron microscopy showed their microporous morphology. Furthermore, the in vitro fungicidal activity was investigated on two fungal strains and the in vitro release curves of the antifungal aldehyde triggered by the pH stimulus were drawn. The theoretical model was developed starting from the hypothesis that the imine-chitosan system, both structurally and functionally, can be assimilated, from a mathematical point of view, with a multifractal object, and its dynamics were analyzed in the framework of the Scale Relativity Theory. Thus, through Riccati-type gauges, two synchronous dynamics, one in the scale space, associated with the fungicidal activity, and the other in the usual space, associated with the antifungal aldehyde release, become operational. Their synchronicity, reducible to the isomorphism of two SL(2R)-type groups, implies, by means of its joint invariant functions, bioactive aldehyde compound release dynamics in the form of "kink–antikink pairs" dynamics of a multifractal type. Finally, the theoretical model was validated through the experimental data. [ABSTRACT FROM AUTHOR]

Chitosan is a naturally originating product that can be applied in many areas due to its biocompatibility, biodegradability, and nontoxic properties. The broad-spectrum antimicrobial activity of chitosan offers great commercial potential for this product. Nevertheless, the antimicrobial activity of chitosan varies, because this activity is associated with its physicochemical characteristics and depends on the type of microorganism. In this review article, the fundamental properties, modes of antimicrobial action, and antimicrobial effects-related factors of chitosan are discussed. We further summarize how microorganisms genetically respond to chitosan. Finally, applications of chitosan-based biomaterials, such as nanoparticles and films, in combination with current clinical antibiotics or antifungal drugs, are also addressed. [ABSTRACT FROM AUTHOR]

Chitosan nanofibrous membranes are prepared via an electrospinning technique and explored as potential wound healing patches. In particular, the effect of a physical or chemical crosslinking treatment on the mat morphological, mechanical, water-related, and biological properties is deeply evaluated. The use of phosphate ions (i.e., physical crosslinking) allows us to obtain smooth and highly homogenous nanofibers with an average size of 190 nm, whereas the use of ethylene glycol diglycidyl ether (i.e., chemical crosslinking) leads to rougher, partially coalesced, and bigger nanofibers with an average dimension of 270 nm. Additionally, the physically crosslinked mats show enhanced mechanical performances, as well as greater water vapour permeability and hydrophilicity, with respect to the chemically crosslinked ones. Above all, cell adhesion and cytotoxicity experiments demonstrate that the use of phosphate ions as crosslinkers significantly improves the capability of chitosan mats to promote cell viability owing to their higher biocompatibility. Moreover, tuneable drug delivery properties are achieved for the physically crosslinked mats by a simple post-processing impregnation methodology, thereby indicating the possibility to enrich the prepared membranes with unique features. The results prove that the proposed approach may lead to the preparation of cheap, biocompatible, and efficient chitosan-based nanofibers for biomedical and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Electrically conductive hydrogels (ECHs), an emerging class of biomaterials, have garnered tremendous attention due to their potential for a wide variety of biomedical applications, from tissue-engineered scaffolds to smart bioelectronics. Along with the development of new hydrogel systems, 3D printing of such ECHs is one of the most advanced approaches towards rapid fabrication of future biomedical implants and devices with versatile designs and tuneable functionalities. In this review, an overview of the state-of-the-art 3D printed ECHs comprising conductive polymers (polythiophene, polyaniline and polypyrrole) and/or conductive fillers (graphene, MXenes and liquid metals) is provided, with an insight into mechanisms of electrical conductivity and design considerations for tuneable physiochemical properties and biocompatibility. Recent advances in the formulation of 3D printable bioinks and their practical applications are discussed; current challenges and limitations of 3D printing of ECHs are identified; new 3D printing-based hybrid methods for selective deposition and fabrication of controlled nanostructures are highlighted; and finally, future directions are proposed. [ABSTRACT FROM AUTHOR]

This paper reports new formulations based on chitosan, citral, and diclofenac sodium salt (DCF). The central idea was to encapsulate an anionic drug into a polycationic hydrogel matrix in order to increase the intermolecular forces between them and thus to ensure slower drug release, while citral was used as a penetration enhancer to assure efficient delivery of the drug. Hydrogels without drug were also synthesized and used as a reference. The structure, morphology, and supramolecular architecture of the drug delivery systems were evaluated by FTIR spectroscopy, scanning electron microscopy, polarized optical microscopy, and wide-angle X-ray diffraction. The drug release kinetics was monitored in vitro by UV-VIS spectroscopy, in physiological conditions, while the enzymatic and hydrolytic degradability of the hydrogels were evaluated in the presence of lysozyme and phosphate buffer saline (PBS), at 37 °C. All of the data revealed that the anionic DCF was strongly anchored into the polycationic matrix and the drug was slowly released over 7 days. Moreover, the release rate can be controlled by simple variation of the molar ratio between the polycationic chitosan and lipophilic citral. [ABSTRACT FROM AUTHOR]

An alternant poly(dihexyl fluorene-co diphenyl oxadiazole) has been synthetized by microwave-assisted oxidative polymerization. The structure has been confirmed by 1H-NMR and FTIR spectroscopies. Gel permeation chromatography indicated high molecular weight and low polydispersity index. DFT calculations suggested a complete separation of HOMO and LUMO orbitals, which were located on fluorene and oxadiazole moiety, respectively. X-ray diffraction, polarized light microscopy, and atomic force microscopy indicated the polymer tendency to stack into a layered morphology with a more compact structure for the films prepared by spin coating. Furthermore, UV-vis and photoluminescence spectroscopies indicated the formation of H-aggregates which played a key role in photoluminescence quenching in solid state. Nevertheless, the good charge mobility gained due to the orbital overlapping in H-aggregates led to excellent electroluminescence, which enabled the development of white OLED devices with outstanding stability. [ABSTRACT FROM AUTHOR]

In the period 2020-2022 as a result of epidemiological measures specific to the COVID-19 pandemic (protective mask, online teaching activity, social distancing) we witnessed a considerable decrease in the number of cases of respiratory viroids in children. With the lifting of prophylactic measures that coincided with the start of physical teaching activities and the onset of the cold season, we have been confronted in pediatric wards with an increase in the incidence of virological infections in the pediatric population. In this article we aim to analyze the particularities of respiratory virological diseases in children in the season 2022 - 2023 both from the etiological and epidemiological point of view and the characteristic clinical forms of the disease. We conducted a retrospective clinical study of cases admitted to the Clinical Departments of Infectious DiseasesPediatrics of the National Institute of Infectious Diseases “Prof. Dr. Matei Bals” in the period October 2022 - March 2023. During this period, we recorded 3.012 cases of respiratory virology in children, which represents the majority of pediatric pathology admitted (72,9 %). The peak incidence of respiratory virology occurred in December (688 cases). From the etiological point of view, most cases were SARS-CoV-2 infections, followed by influenza (predominantly type A), then a smaller number of infections with respiratory syncytial virus (RSV), rhinovirus, adenovirus, metapneumovirus. The most common clinical form of the disease was moderate (66.9%), with severe forms accounting for 10.5%. All pediatric cases of respiratory virology admitted to our wards have evolved favorably, with no deaths. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection is usually a self-limiting viral infection in healthy children. Still, it’s effects on the neonatal population remain largely unknown. There has been evidence of adverse events on neonates, mostly consisting in case reports of patients with severe forms of COVID-19 and also recent cohort studied of the pediatric population including the neonatal subgroup. The clinical presentation appears different in the neonatal patients in contrast with older children, and may manifest also as a life-threatening respiratory infection with systemic complications. In this paper we present a clinical case of a premature boy with a corrected age of 40 weeks at admission to the Pediatric Infectious Diseases Clinical Department IX of the National Institute of Infectious Diseases “Prof. Dr. Matei Bals” with the diagnosis of SARS-CoV-2 infection. The positive diagnosis was established on suggestive clinical picture (fever, dry couch, rhinorrhea, loose stools and inappetence) and confirmed by SARS-CoV-2 rapid antigen test. Laboratory investigations at admission showed only moderate to severe anemia, mild inflammatory syndrome and a mild neonatal hyperbilirubinemia, with normal leukocyte count, normal glycaemia, ionograme and blood gases. Chest x-ray showed moderate interstitial pneumonia. In the second day of admission, after 24h of favorable evolution, with no fever and present appetite, he suddenly presented during defecation a presumptive vasovagal syndrome, with general hypotonia and a short period of desaturation. Laboratory investigations made during the episode showed normal glycaemia, normal ionograme, normal blood gases, moderate-severe anemia and important metabolic acidosis. A new chest x-ray showed evolution of the interstitial pneumonia. We did a blood transfusion and continued antiviral treatment, antibiotic treatment and perfusions. He maintained normal pulmonary and cardiac function for another 6 hours, after which he presented a tonic-clonic seizure and after administration of intrarectal benzodiazepines he presented cardio-pulmonary arrest. He was resuscitated, intubated and sedated and transfer to a children ICU. 2 weeks later after admission in the ICU he was discharged with favorable outcome. The case presented shows that although SARS-CoV-2 infection is often a mild condition in children, COVID-19 in neonates can have an unpredicted course. Rapid evolution to sever forms can be a possible disease outcome. Preterm birth with associated complications like bronchodysplasia or anemia, can predispose to sever evolution of the disease, and this child must be kept safe. There is also a neurotropic potential of the SARS-CoV-2 virus that has to be followed. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The paper focuses on the synthesis and characterization of new drug delivery systems for local therapy. They were prepared by in situ hydrogelation of chitosan biopolymer with nitrosalicylaldehyde in the presence of a model drug, varying the crosslinking density. The structural, supramolecular and morphological characteristics of the systems were studied by FTIR spectroscopy, X-ray diffraction and, POM and SEM microscopy. In vitro release of the drug has been explored in simulated physiological conditions and in vivo release was investigated by the somatic pain model on rats. Information on the biodegradation of the systems was gain by simulating experiments of enzymatic degradation. The systems were biodegradable and showed a prolonged drug release, assuring an in vivo efficient therapeutic effect over 5 days, with no systemic toxicity. All these findings demonstrated that the new hydrogels based on nitrosalicyl-imine-chitosan provides a practical approach for sustained drug delivery for local chemotherapy. [ABSTRACT FROM AUTHOR]