This study looked into the synthesis and study of Dextrane Sulfate-Doxorubicin Nanoparticles (DS-Dox NP) that are sensitive to amylase and show anticoagulant properties. The particles were obtained by the method of solvent replacement. They had a size of 305 ± 58 nm, with a mass ratio of DS:Dox = 3.3:1. On heating to 37 °C, the release of Dox from the particles was equal to 24.2% of the drug contained. In the presence of amylase, this ratio had increased to 42.1%. The study of the biological activity of the particles included an assessment of the cytotoxicity and the effect on hemostasis and antitumor activity. In a study of cytotoxicity on the L929 cell culture, it was found that the synthesized particles had less toxicity, compared to free doxorubicin. However, in the presence of amylase, their cytotoxicity was higher than the traditional forms of the drug. In a study of the effect of DS-Dox NP on hemostasis, it was found that the particles had a heparin-like anticoagulant effect. Antitumor activity was studied on the model of ascitic Zaidel hepatoma in rats. The frequency of complete cure in animals treated with the DS-Dox nanoparticles was higher, compared to animals receiving the traditional form of the drug.
The effect of a range of synthetic charged polymers on alpha-synuclein aggregation and amyloid formation was tested. Sulfated aromatic polymers, poly(styrene sulfonate) and poly(anethole sulfonate), have been found to suppress the fibril formation. In this case, small soluble complexes, which do not bind with thioflavin T, have been formed in contrast to the large stick-type fibrils of free alpha-synuclein. Sulfated polysaccharide (dextran sulfate), as well as sulfated vinylic polymer (poly(vinyl sulfate)) and polycarboxylate (poly(methacrylic acid)), enhanced amyloid aggregation. Conversely, pyridinium polycation, poly(N-ethylvinylpyridinium), switched the mechanism of alpha-synuclein aggregation from amyloidogenic to amorphous, which resulted in the formation of large amorphous aggregates that do not bind with thioflavin T. The obtained results are relevant as a model of charged macromolecules influence on amyloidosis development in humans. In addition, these results may be helpful in searching for new approaches for synucleinopathies treatment with the use of natural polymers.
Degeneration of articular cartilage (AC) is a common healthcare issue that can result in significantly impaired function and mobility for affected patients. The avascular nature of the tissue strongly burdens its regenerative capacity contributing to the development of more serious conditions such as osteoarthritis. Recent advances in bioprinting have prompted the development of alternative tissue engineering therapies for the generation of AC. Particular interest has been dedicated to scaffold-based strategies where 3D substrates are used to guide cellular function and tissue ingrowth. Despite its extensive use in bioprinting, the application of polycaprolactone (PCL) in AC is, however, restricted by properties that inhibit pro-chondrogenic cell phenotypes. This study proposes the use of a new bioprintable poly(ester urea) (PEU) material as an alternative to PCL for the generation of an in vitro model of early chondrogenesis. The polymer was successfully printed into 3D constructs displaying adequate substrate stiffness and increased hydrophilicity compared to PCL. Human chondrocytes cultured on the scaffolds exhibited higher cell viability and improved chondrogenic phenotype with upregulation of genes associated with type II collagen and aggrecan synthesis. Bioprinted PEU scaffolds could, therefore, provide a potential platform for the fabrication of bespoke, pro-chondrogenic tissue engineering constructs.
One of the main issues when orally administering microorganism-based probiotics is the significant loss of bioactivity as they pass through the gastrointestinal (GI) tract. To overcome these issues, here, we propose to encapsulate the probiotic yeast Kluyveromyces lactis on chemically crosslinked gelatin hydrogels as a means to protect the bioactive agents in different environments. Hydrogels were prepared by the chemical crosslinking of gelatin, which is commercially available and inexpensive. This is crucial to ensure scalability and cost-effectiveness. To explore changes in key physicochemical parameters and their impact on cell viability, we varied the concentration of the crosslinking agent (glutaraldehyde) and the gelatin. The synthesized hydrogels were characterized in terms of morphological, physical-chemical, mechanical, thermal and rheological properties. This comprehensive characterization allowed us to identify critical parameters to facilitate encapsulation and enhance cell survival. Mainly due to pore size in the range of 5-10 μm, sufficient rigidity (breaking forces of about 1 N), low brittleness and structural stability under swelling and relatively high shear conditions, we selected hydrogels with a high concentration of gelatin (7.5% (w/v)) and concentrations of the crosslinking agent of 3.0% and 5.0% (w/w) for cell encapsulation. Yeasts were encapsulated with an efficiency of about 10% and subsequently tested in bioreactor operation and GI tract simulated media, thereby leading to cell viability levels that approached 95% and 50%, respectively. After testing, the hydrogels' firmness was only reduced to half of the initial value and maintained resistance to shear even under extreme pH conditions. The mechanisms underlying the observed mechanical response will require further investigation. These encouraging results, added to the superior structural stability after the treatments, indicate that the proposed encapsulates are suitable to overcome most of the major issues of oral administration of probiotics and open the possibility to explore additional biotech applications further.
Proton exchange membranes (PEMs) play a pivotal role in fuel cells; conducting protons from the anode to the cathode within the cell’s membrane electrode assembles (MEA) separates the reactant fuels and prevents electrons from passing through. High proton conductivity is the most important characteristic of the PEM, as this contributes to the performance and efficiency of the fuel cell. However, it is also important to take into account the membrane’s durability to ensure that it canmaintain itsperformance under the actual fuel cell’s operating conditions and serve a long lifetime. The current state-of-the-art Nafion membranes are limited due to their high cost, loss of conductivity at elevated temperatures due to dehydration, and fuel crossover. Alternatives to Nafion have become a well-researched topic in recent years. Aromatic-based membranes where the polymer chains are linked together by aromatic rings, alongside varying numbers of ether, ketone, or sulfone functionalities, imide, or benzimidazoles in their structures, are one of the alternatives that show great potential as PEMs due totheir electrochemical, mechanical, and thermal strengths. Membranes based on these polymers, such as poly(aryl ether ketones) (PAEKs) and polyimides (PIs), however, lack a sufficient level of proton conductivity and durability to be practical for use in fuel cells. Therefore, membrane modifications are necessary to overcome their drawbacks. This paper reviews the challenges associated with different types of aromatic-based PEMs, plus the recent approaches that have been adopted to enhance their properties and performance.
Recently, it has been shown that the reaction mechanism in self-healing diphenyl dichalcogenide-based polymers involves the formation of sulfenyl and selenyl radicals. These radicals are able to attack a neighbouring dichalcogenide bond via a three-membered transition state, leading to the interchange of chalcogen atoms. Hence, the chain mobility is crucial for the exchange reaction to take place. In this work, molecular dynamics simulations have been performed in a set of disulfide- and diselenide-based materials to analyze the effect of the molecular structure in the chain mobility. First of all, a validation of the computational protocol has been carried out, and different simulation parameters like initial guess, length of the molecular chains, size of the simulation box and simulation time, have been evaluated. This protocol has been used to study the chain mobility and also the self-healing capacity, which depends on the probability to generate radicals ( ρ ), the barrier of the exchange reaction ( Δ G ) and the mobility of the chains ( ω ). The first two parameters have been obtained in previous quantum chemical calculations on the systems under study in this work. After analyzing the self-healing capacity, it is concluded that aromatic diselenides (PD-SeSe) are the best candidates among those studied to show self-healing, due to lower reaction barriers and larger ω values.
Gelatin (G) was extracted from the skin of Atlantic cod at different pH of the aqueous phase (pH 3, 4, 5, 8 and 9) and at a temperature of 50 ± 1 °C. The yield of gelatin (G3, G4, G5, G8, and G9, respectively) was 49-55% of the dry raw material. The influence of extraction pH on the physicochemical and functional properties of gelatin was studied. Sample G5 was characterized by higher protein content (92.8%) while lower protein content was obtained for sample G3 (86.5%) extracted under more aggressive conditions. Analysis of the molecular weight distribution showed the presence of α- and β-chains as major components; the molecular weight of the samples ranged between 130 and 150 kDa, with sample G5 having the highest molecular weight. IR spectra of all samples had absorption bands characteristic of fish gelatin. The study of the secondary structure demonstrated higher amounts of ordered triple collagen-like helices for G5 extracted under mild conditions. Accordingly, sample G5 formed gels with high values for the storage modulus and gelling and melting temperatures, which decrease as pH changes into acidic or alkaline regions. In addition, the differential scanning calorimetry data showed that G5 had a higher glass transition temperature and melting enthalpy. Thus, cod skin is an excellent source of gelatin with the necessary physicochemical and functional properties, depending on the appropriate choice of aqueous phase pH for the extraction.
Hydroxypropyl methyl cellulose, HPMC, a hydrophilic polymer, is widely used for the development of extended release hydrophilic matrices and it is also considered as a good contender for the fabrication of 3D printing of matrix tablets. It is often combined with plasticisers to enable extrusion. The aim of the current project was to develop plasticizer-free 3D printed hydrophilic matrices using drug loaded filaments prepared via HME to achieve an in vitro (swelling, erosion and drug release) and in vivo (drug absorption) performance which is analogous to hydrophilic matrix tablets developed through conventional approaches. Additionally, the morphology of the printed tablets was studied using quantitative 3D surface texture studies and the porosity calculated. Filaments were produced successfully and used to produce matrix tablets with acceptable drug loading (95-105%), mechanical and surface texture properties regardless of the employed HPMC grade. The viscosity of HPMC had a discernible impact on the swelling, erosion, HPMC dissolution, drug release and pharmacokinetic findings. The highest viscosity grade (K100M) results in higher degree of swelling, decreased HPMC dissolution, low matrix erosion, decreased drug release and extended drug absorption profile. Overall, this study demonstrated that the drug loaded (glipizide) filaments and matrix tablets of medium to high viscosity grades of HPMC, without the aid of plasticisers, can be successfully prepared. Furthermore, the in vitro and in vivo studies have revealed the successful fabrication of extended release matrices.
The ecological transition is a process the building industry is bound to undertake. This study aimed to develop new bio-based building partition typologies and to determine if they are suitable ecological alternatives to the conventional non-renewable ones used today. This work started with the development of a bio-based epoxy composite board and a waste-based sheep wool acoustic absorbent. Six different partition typologies combining conventional and bio-based materials were analyzed. A drywall partition composed of gypsum plasterboard and mineral wool was used as the baseline. First, a cradle-to-gate life cycle assessment was performed to compare their environmental impacts. Secondly, a mathematical simulation was performed to evaluate their airborne acoustic insulation. The LCA results show a 50% decrease in the amount of CO2 equivalent emitted when replacing plasterboard with bio-composite boards. The bio-composites lower the overall environmental impact by 40%. In the case of the acoustic absorbents, replacing the mineral wool with cellulose or sheep wool decreases the carbon emissions and the overall environmental impact of the partition from 4% and 6%, respectively. However, while the bio-based acoustic absorbents used offer good acoustic results, the bio-composites have a lower airborne acoustic insulation than conventional gypsum plasterboard.
Mixed ionic-electronic conductors, such as poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) are postulated to be the next generation materials in energy storage and electronic devices. Although many studies have aimed to enhance the electronic conductivity and mechanical properties of these materials, there has been little focus on ionic conductivity. In this work, blends based on PEDOT stabilized by the polyelectrolyte poly(diallyldimethylammonium) (PolyDADMA X) are reported, where the X anion is either chloride (Cl), bis(fluorosulfonyl)imide (FSI), bis(trifluoromethylsulfonyl)imide (TFSI), triflate (CF3SO3) or tosylate (Tos). Electronic conductivity values of 0.6 S cm-1 were achieved in films of PEDOT:PolyDADMA FSI (without any post-treatment), with an ionic conductivity of 5 × 10-6 S cm-1 at 70 °C. Organic ionic plastic crystals (OIPCs) based on the cation N-ethyl-N-methylpyrrolidinium (C2mpyr+) with similar anions were added to synergistically enhance both electronic and ionic conductivities. PEDOT:PolyDADMA X / [C2mpyr][X] composites (80/20 wt%) resulted in higher ionic conductivity values (e.g., 2 × 10-5 S cm-1 at 70 °C for PEDOT:PolyDADMA FSI/[C2mpyr][FSI]) and improved electrochemical performance versus the neat PEDOT:PolyDADMA X with no OIPC. Herein, new materials are presented and discussed including new PEDOT:PolyDADMA and organic ionic plastic crystal blends highlighting their promising properties for energy storage applications.