Sepiolite with enhanced chemical reactivity as filler for rubber compounds

Reinforcing fillers are essential ingredients of rubber composites and, among them, inorganic oxides/hydroxides play a crucial role. Silica, with adequate coupling agents, is the best filler for tyre compounds with low energy dissipation and fuel consumption [1]. In recent years, interest has been increasing for biosourced fillers. Sepiolite is one of the most studied, thanks to its nanometric size and high aspect ratio [1-2]. However, sepiolite can hardly behave as a reinforcing filler, without establishing a chemical interaction with the rubber matrix. It is possible to pursue such objective by using an efficient coupling agent. In this study, sepiolite was functionalized with a pyrrole derivative, (2,5-dimethyl-1-(3-(triethoxysilyl) propyl)-1H-pyrrole) (APTESP), by simply mixing in water and heating, performing first evaporation and then the functionalization reaction. The Sepiolite/APTESP adduct was used as reinforcing filler in NR based composites, as the only filler or in a hybrid filler system with carbon black. The composites were prepared via melt blending in internal mixers. Sulfur based crosslinking was carried out and characterization was performed by means of dynamic-mechanical and tensile tests. Results The adduct Sepiolite/APTESP was successfully prepared, by using water as the reaction medium. The amount of APTESP was between 5 and 10% and the functionalization yield was higher than 70%. Sepiolite promoted the dynamic-mechanical reinforcement of the rubber composites, thanks to APTESP as coupling agent. The mechanical percolation threshold in sepiolite, as the only filler in NR, was observed at a sepiolite content of about 15 phr. When sepiolite/APTESP were used in place of CB, similar or lower values of hysteresis were obtained

Bionanocomposites based on a covalent network of chitosan and edge functionalized graphene layers

Graphene has outstanding thermal, mechanical and electronic properties. Bionanocomposites are an emerging class of materials, designed with the aim of achieving advanced structural and functional properties by using biobased polymers. As biopolymer, a great interest is for chitosan (CS), poly (N-acetyl-D-glucosamine), a copolymer of linked 2-acetamido-2-deoxy-D-glucopyranose and 2-amino-2-deoxy-D-glucopyranose. Graphene and graphene related materials are increasingly used for the preparation of bionanocomposites. In this study, a high surface area graphite was edge functionalized with hydroxyl groups (G-OH) through the reaction with KOH. G-CHO, with 4.5 mmol/g of functional group, was prepared from G-OH by means of the Reimer-Tieman reaction. Carbon papers and aerogels were prepared from chitosan and graphene layers with aldehydic edge functional groups (G-CHO) able to form chemical bonds with chitosan and thus to form a crosslinked network. Characterization of the graphitic materials was performed with elemental analysis, titration, X-ray analysis and Raman spectroscopy. CS and G-CHO were mixed with mortar and pestle and carbon papers and aerogels were obtained from a stable acidic water suspension through casting and liophilization, respectively. This work demonstrates that carbon papers and aerogels can be prepared without adopting the traditional oxidation-reduction procedure, avoiding harsh reaction conditions, dangerous and toxic reagents, solvents and catalysts and paves the way for selective modification of graphene layers, exploiting the reactivity of aromatic rings

Electrophysiological evaluation of the peripheral and central pathways in patients with achondroplasia before and during a lower-limb lengthening procedure

In this paper we review the spectrum of spinal and peripheral nerve involvement secondary to achon- droplasia. Alongside conventional and computerised imaging techniques, electrophysiological investiga- tion may represent a useful, non-invasive approach in this clinical setting. Somatosensory evoked poten- tials (SEPs) and magnetic stimulation are valuable tools for studying spinal cord function. Neurophysio- logical abnormalities show a good correlation with the lesion level. Imaging techniques indicate that multiple malformation can affect the patient at the same time and SEPs help to determine the main site of involvement. Interestingly, these techniques are more sensitive than clinical evaluation in document- ing neurological impairment in patients with achon- droplasia prior to the manifestation of unmistakable signs. Callotasi has became a widely used and accept- ed procedure for limb lengthening. Extensive length- ening can be safely performed in patients with achon- droplasia once neurological impairment has been ruled out. In our experience, the presence of elec- trophysiological abnormalities calls for a compre- hensive surgical re-evaluation of the traditional pro- cedure, and sometimes exclusion of patients. Peripheral nerve involvement may occur during limb lengthening, and continuous nerve monitoring pro- vides useful insights into the pathophysiology of nerve damage

Quaternary ammonium chitosans: The importance of the positive fixed charge of the drug delivery systems

As a natural polysaccharide, chitosan has good biocompatibility, biodegradability and biosecurity. The hydroxyl and amino groups present in its structure make it an extremely versatile and chemically modifiable material. In recent years, various synthetic strategies have been used to modify chitosan, mainly to solve the problem of its insolubility in neutral physiological fluids. Thus, derivatives with negative or positive fixed charge were synthesized and used to prepare innovative drug delivery systems. Positively charged conjugates showed improved properties compared to unmodified chitosan. In this review the main quaternary ammonium derivatives of chitosan will be considered, their preparation and their applications will be described to evaluate the impact of the positive fixed charge on the improvement of the properties of the drug delivery systems based on these polymers. Furthermore, the performances of the proposed systems resulting from in vitro and ex vivo experiments will be taken into consideration, with particular attention to cytotoxicity of systems, and their ability to promote drug absorption

2-Methyl-β-cyclodextrin grafted ammonium chitosan: synergistic effects of cyclodextrin host and polymer backbone in the interaction with amphiphilic prednisolone phosphate salt as revealed by NMR spectroscopy

Reduced molecular weight chitosan was quaternized with 2-chloro-N,N-diethylethylamine to obtain a water soluble derivative (N+-rCh). Methylated-β-cyclodextrin (MCD), with 0.5 molar substitution, was covalently linked to N+-rCh through 1,6-hexamethylene diisocyanate spacer to give the derivatized ammonium chitosan N+-rCh-MCD. To shed light on the role of the cyclodextrin pendant in guiding binding interactions with amphiphilic active ingredients, corticosteroid prednisolone phosphate salt (PN) was considered. The deep inclusion of PN into cyclodextrin in PN/MCD model system was pointed out by analysis of 1H NMR complexation shifts, 1D ROESY spectra, and diffusion measurements (DOSY). By using proton selective relaxation rates measurements as investigation tool, the superior affinity of N+-rCh-MCD towards PN was demonstrated in comparison with parent ammonium chitosan N+-rCh

Silver-Russell syndrome. Clinical and etiopathological aspects of a model genomic imprinting entity

Silver-Russell syndrome is characterized by asymmetrical intrauterine growth retardation, with normal head circumference and small, pointed chin, which results in a triangular face. It can also include body asymmetry, among other characteristics. Its global incidence is estimated at 1 in 30 000-100 000 births, even though this figure may be underestimated. In approximately 60 % of cases, a molecular cause can be identified, and the main one is hypomethylation of the paternal allele at the imprinting control region 1 located at 11p15.5-p15.4. It is necessary to make the diagnosis of this entity, exclude differential diagnoses, and know (epi)genotype-phenotype correlations in order to ensure an adequate follow-up, provide available therapeutic options, and offer a timely family genetic counseling. The objective of this article is to describe the current status of the Silver-Russell syndrome, a model of genomic imprinting disorder

Bionanocomposites based on chitosan and few layers graphene. The effect of tailor-made functionalization

Bionanocomposites are an emerging class of material. They are designed and developed to achieve advanced structural and functional properties, by using biobased polymers. Among the bio-polymers, focus is on chitosan (CS), poly (N-acetyl-D-glucosamine), a copolymer of [1,4]-linked 2-acetamido-2-deoxy-D-glucopyranose and 2-amino-2-deoxy-D-glucopyranose. Research is steadily increasing on bionanocomposites with graphene and graphene related materials. It is here presented a research on bionanocomposites based on CS and graphene layers (G). Particular focus of the research was on the integration of the graphene layers in the nanocomposite. Materials were prepared based on the supramolecular interaction between CS and G. The core of the research was then on the edge functionalization of the layers. OH groups were added through the cycloaddition reaction with a biosourced pyrrole compound, serinol pyrrole (SP), carried out with the help of either thermal or mechanical energy, with an atom efficiency up to 96% and a very low E Factor. The preparation of CS/G adducts was very simple, even by using only mortar and pestle. OH groups were also added to the G edges by performing the reaction of G with KOH. The Reimer-Tiemann reaction on the G-OH adduct led to the introduction of aldehydic groups, which promote the crosslinking of CS. The CS/G adducts were characterized by means of wide angle X-ray diffraction, scanning and transmission electron microscopy, Fourier transform infrared, X-ray photoelectron and Raman spectroscopies. Thermal stability of the composites was studied by thermogravimetric analysis. Carbon papers and aerogels were prepared, studying the flexibility and the stability in various solvents in a wide pH range

Jellyfish Polysaccharides for Wound Healing Applications

Jellyfishes are considered a new potential resource in food, pharmaceutical and biomedical industries. In these latter cases, they are studied as source of active principles but are also exploited to produce marine collagen. In the present work, jellyfish skin polysaccharides (JSP) with glycosaminoglycan (GAG) features were extracted from Rhizostoma pulmo, a main blooming species of Mediterranean Sea, massively augmented by climate leaded “jellyfishication” of the sea. Two main fractions of R. pulmo JSP (RP-JSPs) were isolated and characterized, namely a neutral fraction (RP-JSP1) and a sulphate rich, negatively charged fraction (RP-JSP2). The two fractions have average molecular weights of 121 kDa and 590 kDa, respectively. Their sugar composition was evaluated through LC-MS analysis and the result confirmed the presence of typical GAG saccharides, such as glucose, galactose, glucosamine and galactosamine. Their use as promoters of wound healing was evaluated through in vitro scratch assay on murine fibroblast cell line (BALB/3T3 clone A31) and human keratinocytes (HaCaT). Both RP-JSPs demonstrated an effective confluency rate activity leading to 80% of scratch repair in two days, promoting both cell migration and proliferation. Additionally, RP-JSPs exerted a substantial protection from oxidative stress, resulting in improved viability of treated fibroblasts exposed to H2O2. The isolated GAG-like polysaccharides appear promising as functional component for biomedical skin treatments, as well as for future exploitation as pharmaceutical excipients

Repurposing of plasminogen: An orphan medicinal product suitable for SARS-CoV-2 inhalable therapeutics

The SARS-CoV-2 infection is associated with pulmonary coagulopathy, which determines the deposition of fibrin in the air spaces and lung parenchyma. The resulting lung lesions compromise patient pulmonary function and increase mortality, or end in permanent lung damage for those who have recovered from the COVID-19 disease. Therefore, local pulmonary fibrinolysis can be efficacious in degrading pre-existing fibrin clots and reducing the conversion of lung lesions into lasting scars. Plasminogen is considered a key player in fibrinolysis processes, and in view of a bench-to-bedside translation, we focused on the aerosolization of an orphan medicinal product (OMP) for ligneous conjunctivitis: human plasminogen (PLG-OMP) eye drops. As such, the sterile and preservative-free solution guarantees the pharmaceutical quality of GMP production and meets the Ph. Eur. requirements of liquid preparations for nebulization. PLG-OMP aerosolization was evaluated both from technological and stability viewpoints, after being submitted to either jet or ultrasonic nebulization. Jet nebulization resulted in a more efficient delivery of an aerosol suitable for pulmonary deposition. The biochemical investigation highlighted substantial protein integrity maintenance with the percentage of native plasminogen band > 90%, in accordance with the quality specifications of PLG-OMP. In a coherent way, the specific activity of plasminogen is maintained within the range 4.8–5.6 IU/mg (PLG-OMP pre-nebulization: 5.0 IU/mg). This is the first study that focuses on the technological and biochemical aspects of aerosolized plasminogen, which could affect both treatment efficacy and clinical dosage delivery. Increasing evidence for the need of local fibrinolytic therapy could merge with the availability of PLG-OMP as an easy handling solution, readily aerosolizable for a fast translation into an extended clinical efficacy assessment in COVID-19 patients

Structure determination, thermal stability and dissolution rate of 6-indomethacin

The structure solution of the δ-polymorph of indomethacin was obtained using three-dimensional electron diffraction. This form shows a significantly enhanced dissolution rate compared with the more common and better studied α- and γ-polymorphs, indicating better biopharmaceutical properties for medicinal applications. The structure was solved in non-centrosymmetric space group P21 and comprises two molecules in the asymmetric unit. Packing and molecule conformation closely resemble indomethacin methyl ester and indomethacin methanol solvate. Knowledge of the structure allowed the rational interpretation of spectroscopic IR and Raman data for δ-polymorph and a tentative interpretation for still unsolved indomethacin polymorphs. Finally, we observed a solid–solid transition from δ-polymorph to α-polymorph that can be driven by similarities in molecular conformation