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Deferoxamine (DFO) is a water-soluble iron chelator used pharmacologically for the management of patients with transfusional iron overload. However, DFO is not cell-permeable and has a short plasma half-life, which necessitates lengthy parenteral administration with an infusion pump. We previously reported the synthesis of chitosan (CS) nanoparticles for sustained slow release of DFO. In the present study, we developed solid dispersions and nanoparticles of a carboxymethyl water-soluble chitosan derivative (CMCS) for improved DFO encapsulation and release. CS dispersions and nanoparticles with DFO have been prepared by ironical gelation using sodium triphosphate (TPP) and were examined for comparison purposes. The successful presence of DFO in CMCS polymeric dispersions and nanoparticles was confirmed through FTIR measurements. Furthermore, the formation of CMCS nanoparticles led to inclusion of DFO in an amorphous state, while dispersion of DFO in the polymeric matrix led to a decrease in its crystallinity according to X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results. An in vitro release assay indicated sustained release of DFO from CS and CMCS nanoparticles over 48 h and 24 h, respectively. Application of CMCS-DFO dispersions to murine RAW 264.7 macrophages or human HeLa cervical carcinoma cells triggered cellular responses to iron deficiency. These were exemplified in the induction of the mRNA encoding transferrin receptor 1, the major iron uptake protein, and the suppression of ferritin, the iron storage protein. Our data indicate that CMCS-DFO nanoparticles release bioactive DFO that causes effective iron chelation in cultured cells.

Chitosan is a polysaccharide vastly examined in polymer science for its unique structure. In the present study, CS was derivatized with 2-methoxy-4vinylphenol (MVP) in four different ratios through a free radical reaction. The CS-MVP derivatives were characterized through FTIR, 1H-NMR, XRD, swelling, and solubility measurements. Owing to the enhanced antioxidant character of the MVP monomer, the antioxidant activity of the CS-MVP derivatives was assessed. In the optimum CS-MVP ratio, blends between CS and CS-MVP were prepared in ratios of 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80, and 10:90 w / w , and their miscibility was examined by scanning electron microscopy (SEM) and viscosity measurements. In the optimum ratios, highly concentrated inks were prepared, and their viscosity measurements revealed the successful formation of highly viscous gels with shear thinning behavior. These inks could be appropriate candidates for biomedical and drug delivery applications.

In the present study, the blends of CS and Vanillin-CS derivative (VACS) were utilized for the preparation of printable inks for their application in three-dimensional (3D) printing procedures. Despite the synergic interaction between the blends, the addition of ι-carrageenan (iCR) as a thickening agent was mandatory. Their viscosity analysis was conducted for the evaluation of the optimum CS/VACS ratio. The shear thinning behavior along with the effect of the temperature on viscosity values were evident. Further characterization of the 3D-printed structures was conducted. The effect of the CS/VACS ratio was established through swelling and contact angle measurements. An increasing amount of VACS resulted in lower swelling ability along with higher hydrophobicity. Fluticasone propionate (FLU), a crystalline synthetic corticosteroid, was loaded into the CS/VACS samples. The drug was loaded in its amorphous state, and consequently, its in vitro release was significantly enhanced. An initial burst release, followed by a sustained release profile, was observed.

In the current work, a series of PCL polyesters with different molecular weights was synthesized and used for the fabrication of nanofibrous patches via electrospinning, as sustained release matrices for leflunomide's active metabolite, teriflunomide (TFL). The electrospinning conditions for each sample were optimized and it was found that only one material with high Mn (71,000) was able to produce structures with distinct fibers devoid of the presence of beads. The successful preparation of the fibers was determined by scanning electron microscopy (SEM).TFL (10, 20 and 30 wt%) in three different concentrations was incorporated into the prepared nanofibers, which were used in in vitro drug release experiments. The drug-loaded nanofibrous formulations were further characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffractometry (XRD).It was found that TFL was incorporated in an amorphous form inside the polymeric nanofibers and that significant molecular interactions were formed between the drug and the polyester. Additionally, in vitro dissolution studies showed that the PCL/TFL-loaded nanofibers exhibit a biphasic release profile, having an initial burst release phase, followed by a sustained release until 250 h. Finally, a kinetic analysis of the obtained profiles revealed that the drug release was directly dependent on the amount TFL incorporated into the nanofibers.

Synthetic polymers have been an integral part of modern society since the early 1960s. Besides their most well-known applications to the public, such as packaging, construction, textiles and electronics, synthetic polymers have also revolutionized the field of medicine. Starting with the first plastic syringe developed in 1955 to the complex polymeric materials used in the regeneration of tissues, their contributions have never been more prominent. Decades of research on polymeric materials, stem cells, and three-dimensional printing contributed to the rapid progress of tissue engineering and regenerative medicine that envisages the potential future of organ transplantations. This perspective discusses the role of synthetic polymers in tissue engineering, their design and properties in relation to each type of application. Additionally, selected recent achievements of tissue engineering using synthetic polymers are outlined to provide insight into how they will contribute to the advancement of the field in the near future. In this way, we aim to provide a guide that will help scientists with synthetic polymer design and selection for different tissue engineering applications.

3D printing, or additive manufacturing, has gained considerable interest due to its versatility regarding design as well as in the large choice of materials. It is a powerful tool in the field of personalized pharmaceutical treatment, particularly crucial for pediatric and geriatric patients. Polysaccharides are abundant and inexpensive natural polymers, that are already widely used in the food industry and as excipients in pharmaceutical and cosmetic formulations. Due to their intrinsic properties, such as biocompatibility, biodegradability, non-immunogenicity, etc., polysaccharides are largely investigated as matrices for drug delivery. Although an increasing number of interesting reviews on additive manufacturing and drug delivery are being published, there is a gap concerning the printing of polysaccharides. In this article, we will review recent advances in the 3D printing of polysaccharides focused on drug delivery applications. Among the large family of polysaccharides, the present review will particularly focus on cellulose and cellulose derivatives, chitosan and sodium alginate, printed by fused deposition modeling and extrusion-based printing.

In the present study, chitosan (CS) reacted with vanillin through a Schiff base reaction forming the vanillin-CS (VACS) derivative. FTIR and 1 H NMR spectra confirmed the derivatization of CS, the enhanced swelling behavior was long-established while XRD measurement stated the semicrystalline nature of the VACS derivative. In a further step, blends between CS and VACS were prepared in ratios CS/VACS 90/10 up to 10/90 w/w and the formation of hydrogen bonds was noticed through FTIR and XRD measurements. Structural optimizations were performed within the framework of density functional theory and interaction energies E int were calculated. Collectively, these results along with viscosity measurements and SEM images prove the miscibility of CS/VACS blends. In the optimum CS/VACS ratios, inks for 3D printing application were prepared in different concentrations (3%w/v, 4%w/v, 5%w/v, 6%w/v). The augmentation of the samples' viscosity values influenced by the polymeric concentration was assessed while their thereafter printing application was conducted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The compound of chitin is the second most important and abundant natural biopolymer in the world. The main extraction and exploitation sources of this natural polysaccharide polymer are mainly crustaceans species, such as shrimps and crabs. Chitosan (CS) (poly-β-(1 → 4)-2-amino-2-deoxy-d-glucose) can be derived from chitin and can be mentioned as a compound that has high value-added applications due to its wide variety of uses, including pharmaceutical, biomedical, and cosmetics applications, food etc. Furthermore, chitosan is a biopolymer that can be used for adsorption applications because it contains amino and hydroxyl groups in its chemical structure (molecules), resulting in possible interactions of adsorption between chitosan and pollutants (uranium, mercury, rare earth elements (REEs), phenols, etc.). However, adsorption is a very effective, fast, simple, and low-cost process. This review article places emphasis on recent demonstrated research papers (2014-2020) where the chemical modifications of CS are explained briefly (grafting, cross-linking etc.) for the uptake of uranium, mercury, and REEs in synthesized aqueous solutions. Finally, figures and tables from selected synthetic routes of CS are presented and the effects of pH and the best mathematical fitting of isotherm and kinetic equations are discussed. In addition, the adsorption mechanisms are discussed.

Accruing evidence suggest that COVID-19 is more fatal for males and minorities than other sub-populations. In this paper, we study medical dilemmas pertaining to the allocation of medical resources to evaluate whether existing social biases correspond to the demographic disparities of the pandemic. We develop and implement a choice experiment in which participants decide how to allocate scarce medical resources among COVID-19 patients with diverse demographic attributes. We find that participants violate optimal resource allocation significantly more often for the benefit of females. Males are almost half as likely to receive lifesaving resources even if these are medically more beneficial for them. We also find that participants are less likely to assign resources to patients with high compared to low income. Last, we find no evidence of patients' race affecting allocation preferences., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Michailidou.)

In the present study, chitosan (CS) and pectin (PEC) were utilized for the preparation of 3D printable inks through pneumatic extrusion for biomedical applications. CS is a polysaccharide with beneficial properties; however, its printing behavior is not satisfying, rendering the addition of a thickening agent necessary, i.e., PEC. The influence of PEC in the prepared inks was assessed through rheological measurements, altering the viscosity of the inks to be suitable for 3D printing. 3D printing conditions were optimized and the effect of different drying procedures, along with the presence or absence of a gelating agent on the CS-PEC printed scaffolds were assessed. The mean pore size along with the average filament diameter were measured through SEM micrographs. Interactions among the characteristic groups of the two polymers were evident through FTIR spectra. Swelling and hydrolysis measurements confirmed the influence of gelation and drying procedure on the subsequent behavior of the scaffolds. Ascribed to the beneficial pore size and swelling behavior, fibroblasts were able to survive upon exposure to the ungelated scaffolds.

Chitosan (CS) is a natural polysaccharide, widely studied in the past due to its unique properties such as biocompatibility, biodegradability and non-toxicity. Chemical modification of CS is an effective pathway to prepare new matrices with additional functional groups and improved properties, such as increment of hydrophilicity and swelling rate, for drug delivery purposes. In the present study, four derivatives of CS with trans-aconitic acid (t-Acon), succinic anhydride (Succ), 2-hydroxyethyl acrylate (2-HEA) and acrylic acid (AA) were prepared, and their successful grafting was confirmed by FTIR and 1 H-NMR spectroscopies. Neat chitosan and its grafted derivatives were fabricated for the encapsulation of fluticasone propionate (FLU) and salmeterol xinafoate (SX) drugs, used for chronic obstructive pulmonary disease (COPD), via the ionotropic gelation technique. Scanning electron microscopy (SEM) micrographs demonstrated that round-shaped microparticles (MPs) were effectively prepared with average sizes ranging between 0.4 and 2.2 μm, as were measured by dynamic light scattering (DLS), while zeta potential verified in all cases their positive charged surface. FTIR spectroscopy showed that some interactions take place between the drugs and the polymeric matrices, while X-ray diffraction (XRD) patterns exhibited that both drugs were encapsulated in MPs' interior with a lower degree of crystallinity than the neat drugs. In vitro release studies of FLU and SX exposed a great amelioration in the drugs' dissolution profile from all modified CS's MPs, in comparison to those of neat drugs. The latter fact is attributed to the reduction in crystallinity of the active substances in the MPs' interior.

In the present study, a chitosan (CS) derivative with the 2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SDAEM) zwitterionic monomer was prepared through chemical modification. The successful synthesis of CS-SDAEM was confirmed by Fourier-transform Infrared (FTIR) and Nuclear Magnetic Resonance ( 1 H-NMR) spectroscopies. Its crystallinity was studied by X-ray Diffraction (XRD), while in vitro cytotoxicity and cell viability assays established its biocompatibility. Filtered fresh pomegranate juice (PJ) was loaded in nanoparticles of neat CS and its derivative via ionic gelation method. Dynamic Light Scattering (DLS) revealed nanoparticles sizes varying between 426 nm and 4.5 μm, indicating a size-dependence on the polymer concentration used during encapsulation. High-performance liquid chromatography coupled with photodiode array and electrospray ionization mass spectrometry detection (LC-PDA-ESI/MS) revealed that PJ active compounds were successfully and in sufficient amounts encapsulated in the nanoparticles interior, whereas XRD indicated a crystalline structure alteration after nanoencapsulation. The resulted PJ-loaded nanoparticles were further utilized for the preparation of innovative O/W cosmetic emulsions. All produced emulsions exhibited good pH and viscosity stability for up to 90 days, while the sun protection factor (SPF) was enhanced due to the presence of the PJ. Enhanced antioxidant and antimicrobial properties due to the phenolic compounds of PJ were also observed.

Chitosan (CS) is a hemi-synthetic cationic linear polysaccharide produced by the deacetylation of chitin. CS is non-toxic, highly biocompatible, and biodegradable, and it has a low immunogenicity. Additionally, CS has inherent antibacterial properties and a mucoadhesive character and can disrupt epithelial tight junctions, thus acting as a permeability enhancer. As such, CS and its derivatives are well-suited for the challenging field of ocular drug delivery. In the present review article, we will discuss the properties of CS that contribute to its successful application in ocular delivery before reviewing the latest advances in the use of CS for the development of novel ophthalmic delivery systems. Colloidal nanocarriers (nanoparticles, micelles, liposomes) will be presented, followed by CS gels and lenses and ocular inserts. Finally, instances of CS coatings, aiming at conferring mucoadhesiveness to other matrixes, will be presented.

The aim of this work was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with 2-acrylamido-2-methyl-1-propanesulfonic acid (AAMPS) and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSP) as appropriate nanocarriers for the simultaneous ocular administration of dexamethasone sodium phosphate (DxP) and chloramphenicol (CHL). The derivatives CS-AAMPS and CS-MEDSP have been synthesized by free-radical polymerization and their structure has been proved by Fourier-Transformed Infrared Spectroscopy (FT-IR) spectroscopy. Both derivatives exhibited low cytotoxicity, enhanced mucoadhesive properties and antimicrobial activity against Staphylococcus aureus ( S.aureus ) and Escherichia coli ( E. coli ). Encapsulation was performed via ionic crosslinking gelation using sodium tripolyphosphate (TPP) as the crosslinking agent. Dynamic light scattering measurements (DLS) showed that the prepared nanoparticles had bimodal distribution and sizes ranging from 50-200 nm and 300-800 nm. Drugs were encapsulated in their crystalline (CHL) or amorphous (DexSP) form inside nanoparticles and their release rate was dependent on the used polymer. The CHL dissolution rate was substantially enhanced compared to the neat drug and the release time was extended up to 7 days. The release rate of DexSP was much faster than that of CHL and was prolonged up to 3 days. Drug release modeling unveiled that diffusion is the main release mechanism for both drugs. Both prepared derivatives and their drug-loaded nanoparticles could be used for extended and simultaneous ocular release formulations of DexSP and CHL drugs.

Chitosan (CS) is a polymer extensively used in drug delivery formulations mainly due to its biocompatibility and low toxicity. In the present study, chitosan was used for nanoencapsulation of a budesonide (BUD) drug via the well-established ionic gelation technique and a slight modification of it, using also poly(vinyl alcohol) (PVA) as a surfactant. Scanning electron microscopy (SEM) micrographs revealed that spherical nanoparticles were successfully prepared with average sizes range between 363 and 543 nm, as were measured by dynamic light scattering (DLS), while zeta potential verified their positive charged surface. X-ray diffraction (XRD) patterns revealed that BUD was encapsulated in crystalline state in nanoparticles but with a lower degree of crystallinity than the neat drug, which was also proven by differential scanning calorimetry (DSC) and melting peak measurements. This could be attributed to interactions that take place between BUD and CS, which were revealed by FTIR and by an extended computational study. An in vitro release study of budesonide showed a slight enhancement in the BUD dissolution profile, compared to the neat drug. However, drug release was substantially increased by introducing PVA during the nanoencapsulation procedure, which is attributed to the higher amorphization of BUD on these nanoparticles. The release curves were analyzed using a diffusion model that allows estimation of BUD diffusivity in the nanoparticles.

In the present study polymer blends based on chitosan (CS) and its derivatives with trans-aconitic (t-Acon) acid and another with trimellitic (TRM) anhydride, were prepared for topical wound delivery of chloramphenicol (CHL). FT-IR spectroscopy revealed the successful grafting of t-Acon acid or TRM anhydride into CS macromolecules at molar ratios 1:1 and 1:0.5, while powder X-ray diffraction (XRD) analysis showed that the prepared materials were amorphous. Neat chitosan and its grafted derivatives were mixed in different ratios (25/75, 50/50 and 75/25 w/w) in order to prepare suitable blends. Scanning electron microscopy (SEM) showed that the formed blends after freeze-drying had a sponge-like structure, while thermogravimetric analysis (TGA) verified their thermal stability. All blends are miscible in studied compositions and have extensive swelling and much better mechanical properties than neat CS. In a further step, the obtained porous sponges prepared from CS/CS-derivatives 50/50 w/w were loaded with Chloramphenicol (10, 20 and 30 wt%), a broad-spectrum antibiotic, and the prepared dressings were evaluated in terms of FT-IR, XRD, SEM, and in vitro drug dissolution. An initial burst release followed by a quasi-Fickian diffusion driven sustained release phase was observed while the addition of chloramphenicol gives high antimicrobial properties to all dressings., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: The aim of this study is the presentation of the imaging findings in patients with pulmonary embolism, the diagnosis of which was made with the use of helical computed tomography., Material and Methods: The lung CT scans of 14 patients were retrospectively studied. The presence of hypoattenuating thrombus within the lumen of one or more pulmonary arterial branches was considered as the imaging criterion for the diagnosis of pulmonary embolism., Results: Emboli within the lumen of 1st order branches were found in 2 patients, within the lumen of 2nd order branches in 8 patients, into the lumen of 3rd order branches (lobar) in 10 patients and into the lumen of 4th order branches (segmental) in 6 patients. No emboli were detected in subsegmental or more peripheral branches. Concomitant, secondary findings were the presence of unilateral pleural effusion, areas of pulmonary oligaemia and the presence of a wedge-shaped, pleural-based opacity, indicative of a pulmonary infarct., Conclusion: In conclusion, we were able to make the diagnosis of pulmonary embolism through the direct visualization of intraluminal emboli up until the segmental level, as well as of concomitant, accessory findings of pulmonary embolism.

TRAF2 mediates activation of the transcription factors NF-kappaB and AP1 by TNF. A yeast two-hybrid screen of a human cDNA library identified a ubiquitin specific protease homologue (USP31) as a TRAF2-interacting protein. Two cDNAs encoding for USP31 were identified. One cDNA encodes a 1035-amino acid long isoform of USP31 (USP31, long isoform) and the other a 485-amino acid long isoform of USP31 (USP31S1, short isoform). USP31 and USP31S1 share a common amino terminal region with homology to the catalytic region of known deubiquitinating enzymes. Enzymatic assays demonstrated that USP31 but not USP31S1 possess deubiquitinating activity. Furthermore, it was shown that USP31 has a higher activity towards lysine-63-linked as compared to lysine-48-linked polyubiquitin chains. Overexpression of USP31 in HEK 293T cells inhibited TNFalpha, CD40, LMP1, TRAF2, TRAF6 and IKKbeta-mediated NF-kappaB activation, but did not inhibit Smad-mediated transcription activation. In addition, both USP31 isoforms interact with p65/RelA. Our data support a role for USP31 in the regulation of NF-kappaB activation by members of the TNF receptor superfamily.