Biodegradable Guar-Gum-Based Super-Porous Matrices for Gastroretentive Controlled Drug Release in the Treatment of Helicobacter pylori: A Proof of Concept.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Assessment of the denaturation of collagen protein concentrates using different techniques.

The use of collagen and gelatin in the field of regenerative medicine is widely extended. However, most of the studies in this topic are focused on the scaffolds' properties, but only a few are related to the properties of the raw material used. The raw material analysis not only consists of a study of the composition, but also of the denaturation degree that can influence the processing and properties of the structure of the scaffold. Thus, the denaturation degree analysis of different collagen proteins was performed and assessed by the comparison of four different methods: differential scanning calorimetry (DSC), Fourier transform Infrared Spectroscopy (FTIR) and circular dichroism (CD) spectra and sulfhydryls content analysis. DSC measurements put forward a glass transition between 88°C and 95°C as well as from the FTIR measurements; the characteristic peaks for proteins are evidenced. However, from the sulfur content, only a small proportion of free sulfhydryls are present with respect to their total amount. In addition, CD spectra allow to estimate the secondary structure of the protein by the analysis of the α-helix and ß-strand and also quantify the denaturation degree with the 'positive/negative ratio' (RPN) from the CD profiles, obtaining values in the range between 25% and 100%.

Development of superabsorbent soy protein-based bioplastic matrices with incorporated zinc for horticulture.

BACKGROUND: The use of superabsorbent materials in horticulture has spread recently. These materials, which can retain water and release it as crops need it, have strong advantages such as the efficient use of water in periods of drought. However, these materials are made of synthetic polymers, which present problems of degradability and, sometimes, toxicity. For this reason, the main objective of this work is the development of biodegradable superabsorbent bioplastic (SAB) matrices using a soy protein isolate (SPI) as raw material. Zinc is also incorporated into these bioplastic matrices as an essential micronutrient for plants, to increase their added value. RESULTS: The incorporation of zinc chelated with 2,2',2″,2‴-(Ethene-1,2-diyldinitrilo)tetraacetic acid (Zn EDTA) (a salt with which the micronutrient is incorporated) into soy protein-based bioplastic matrices improved their superabsorbent capacity and provided a controlled release of water and nutrients to the crops. CONCLUSIONS: The results show the strong potential for the use of these bioplastic matrices in horticulture as superabsorbent materials that can release nutrients in a controlled manner. © 2019 Society of Chemical Industry.

Development of pea protein-based bioplastics with antimicrobial properties.

BACKGROUND: In the present work, bioplastics from renewable polymers were studied in order to reduce the huge generation of plastic wastes, causing an environmental problem that continues owing to the increasing demand for plastic products. RESULTS: Bioplastics with much better antimicrobial properties, in particular against Gram-positive bacteria, were obtained with the addition of nisin to the initial protein/plasticizer mixture. However, the addition of nisin produces more rigid but less deformable bioplastics (higher Young's modulus but lower strain at break). CONCLUSION: The results obtained are useful to demonstrate the antimicrobial properties of pea protein-based bioplastics by adding nisin and make them suitable as potential candidates to replace conventional plastics in food packaging. © 2016 Society of Chemical Industry.

Characterization of emulgels formulated with phycocyanin and diutan gum as a novel approach for biocompatible delivery systems.

Phycocyanin (PC), a protein derived from algae, is non-toxic and biocompatible. Due to its environmental and sustainable properties, it has been studied as an alternative stabilizer for food emulsions. In this sense, the main objective of this work is to evaluate the effectiveness of PC and its use in combination with diutan gum (DG), a biological macromolecule, to prepare emulgels formulated with avocado oil. Z-potential measurements show that the optimum pH for working with PC is 2.5. Furthermore, the system exhibited a structured interface at this pH. The surface tension did not decrease further above 1.5 wt% PC. Interestingly, emulsions formulated with >1.5 wt% PC showed recoalescence immediately after preparation. Although 1.5 wt% had the smallest droplet size, this emulsion underwent creaming due to the low viscosity of the system. DG was used in combination with PC to increase viscosity and reduce creaming. As little as 0.1 wt% DG was sufficient to form an emulgel when incorporated into the previous emulsion, which exhibited pseudoplastic behaviour and viscoelastic properties with very low creaming rates. However, the use of PC in combination with DG resulted in a non-aggregated and stable emulgel with 1.5 wt% PC and 0.1 wt% DG.

A Thermoresponsive injectable drug delivery system of chitosan/ß-glycerophosphate with gellan gum/alginate microparticles.

The development of new Drug Delivery Systems (DDS) by incorporating microparticles within hydrogels can prolong the release rate of drugs and/or other bioactive agents. In this study, we combined gellan gum/alginate microparticles within a thermoresponsive chitosan (Ch) hydrogel with ß-Glycerophosphate (ß-GP), designing the system to be in the sol state at 21 °C and in the gel state at 37 °C to enable the injectability of the system. The system was in the sol state between 10 °C and 21 °C. Higher concentrations of ß-GP (0, 2, 3, 4, 5 w/v%) and microparticles (0, 2 and 5 w/v%) allowed a faster sol-gel transition with higher mechanical strength at 37 °C. However, the sol-gel transition was not instantaneous. The release profile of methylene blue (MB) from the microparticles was significantly affected by their incorporation in Ch/ß-GP hydrogels, only allowing the release of 60-70 % of MB for 6 days, while the microparticles alone released all the MB in 48 h. The proposed system did not present cytotoxicity to VERO cell lines as a preliminary assay, with the Ch/ß-GP/GG:Alg having >90 % of cellular viability. The proposed Ch/ß-GP system proved to have a delaying effect on drug release and biocompatible properties, being a promising future DDS.

Effect of different crosslinking agents on hybrid chitosan/collagen hydrogels for potential tissue engineering applications.

Tissue engineering (TE) demands scaffolds that have the necessary resistance to withstand the mechanical stresses once implanted in our body, as well as excellent biocompatibility. Hydrogels are postulated as interesting materials for this purpose, especially those made from biopolymers. In this study, the microstructure and rheological performance, as well as functional and biological properties of chitosan and collagen hydrogels (CH/CG) crosslinked with different coupling agents, both natural such as d-Fructose (F), genipin (G) and transglutaminase (T) and synthetic, using a combination of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with N-hydroxysuccinimide (EDC/NHS) will be assessed. FTIR tests were carried out to determine if the proposed crosslinking reactions for each crosslinking agent occurred as expected, obtaining positive results in this aspect. Regarding the characterization of the properties of each system, two main trends were observed, from which it could be established that crosslinking with G and EDC-NHS turned out to be more effective and beneficial than with the other two crosslinking agents, producing significant improvements with respect to the base CH/CG hydrogel. In addition, in vitro tests demonstrated the potential application in TE of these systems, especially for those crosslinked with G, T and EDC-NHS.

Soy Protein Isolate as Emulsifier of Nanoemulsified Beverages: Rheological and Physical Evaluation.

The production of biologically active molecules or the addition of new bioactive ingredients in foods, thereby producing functional foods, has been improved with nanoemulsion technology. In this sense, the aim of this work was to develop nanoemulsified beverages as potential candidates for the encapsulation of bioactive compounds, whose integrity and release across the intestinal tract are controlled by the structure and stability of the interfaces. To achieve this, firstly, a by-product rich-in protein has been evaluated as a potential candidate to act as an emulsifier (chemical content, amino acid composition, solubility, ζ-potential and surface tension were evaluated). Later, emulsions with different soy protein isolate concentrations (0.5, 1.0, 1.5 and 2.0 wt%), pH values (2, 4, 6 and 8) and homogenization pressures (100, 120 and 140 PSI) were prepared using a high-pressure homogenizer after a pre-emulsion formation. Physical (stability via Backscattering and drop size evolution) and rheological (including interfacial analysis) characterizations of emulsions were carried out to characterize their potential as delivery emulsion systems. According to the results obtained, the nanoemulsions showed the best stability when the protein concentration was 2.0 wt%, pH 2.0 and 120 PSI was applied as homogenization pressure.

Type-A Gelatin-Based Hydrogel Infiltration and Degradation in Titanium Foams as a Potential Method for Localised Drug Delivery.

A gelatin-based hydrogel was infiltrated and degraded-released in two different titanium foams with porosities of 30 and 60 vol.% (Ti30 and Ti60 foams) and fabricated by the space holder technique to evaluate its potential to act as an innovative, alternative, and localised method to introduce both active pharmaceutical ingredients, such as antibiotics and non-steroidal anti-inflammatory drugs, and growth factors, such as morphogens, required after bone-tissue replacement surgeries. In addition, the kinetic behaviour was studied for both infiltration and degradation-release processes. A higher infiltration rate was observed in the Ti60 foam. The maximum infiltration hydrogel was achieved for the Ti30 and Ti60 foams after 120 min and 75 min, respectively. Further, both processes followed a Lucas-Washburn theoretical behaviour, typical for the infiltration of a fluid by capillarity in porous channels. Regarding the subsequent degradation-release process, both systems showed similar exponential degradation performance, with the full release from Ti60 foam (80 min), versus 45 min for Ti30, due to the greater interconnected porosity open to the surface of the Ti60 foam in comparison with the Ti30 foam. In addition, the optimal biocompatibility of the hydrogel was confirmed, with the total absence of cytotoxicity and the promotion of cell growth in the fibroblast cells evaluated.

Functionalization Routes for Keratin from Poultry Industry Side-Streams-Towards Bio-Based Absorbent Polymers.

Keratin is a largely available protein that can be obtained from the ca. 3 million tons of feathers that the European poultry industry produces as a side-stream. Here, the functionalization of keratin from poultry feathers was evaluated using a one- versus two-stage process using two functionalization agents (succinic anhydride-SA and ethylene dianhydride-EDTAD). The functionalization resulted in the keratin having improved liquid swelling capacities, reaching up to 400%, 300%, and 85% increase in water, saline, and blood, respectively, compared to non-functionalized keratin. The highest swelling was obtained for samples functionalized with EDTAD (one-stage process), while the highest saline uptake was noted for samples processed with 25 wt% SA (two-stage process). Swelling kinetics modeling indicated that the water uptake by the functionalized samples takes place in two steps, and the EDTAD samples showed the highest diffusivity. It is demonstrated that the one-stage functionalization of keratin utilizing EDTAD results in better performance than two-stages, which allows for resource-saving and, thereby, protecting the environment. The results show some potential for the keratin to be utilized as liquid absorbent materials in water, saline, and blood uptake applications. Using keratin from side-streams is an advantage from a sustainability perspective over biomacromolecules that need to be extracted from virgin biomass.

Porous Thermoformed Protein Bioblends as Degradable Absorbent Alternatives in Sanitary Materials.

Protein-based porous absorbent structures can be processed and assembled into configurations suitable for single-use, biodegradable sanitary materials. In this work, a formulation based on a mixture of proteins available as industrial coproducts is processed into continuous porous structures using extrusion and assembled using conventional thermal methods. The experimental design led to formulations solely based on zein-gluten protein bioblends that could be manufactured as liquid absorbent pellets, compressed pads, and/or porous films. The processing versatility is attributed to the synergistic effect of zein as a low viscosity thermoformable protein with gluten as a readily cross-linkable high molecular weight protein. The capillary-driven sorption, the biodegradability of the materials, and the possibility to assemble the products as multilayer components provide excellent performance indicators for their use as microplastic-free absorbents. This work shows the potential of biopolymers for manufacturing sustainable alternatives to current nonbiodegradable and highly polluting disposable items such as pads and diapers.

Valorization of Honduran Agro-Food Waste to Produce Bioplastics.

The development of biodegradable plastics and eco-friendly biomaterials derived from renewable resources is crucial for reducing environmental damage. Agro-industrial waste and rejected food can be polymerized into bioplastics, offering a sustainable solution. Bioplastics find use in various industries, including for food, cosmetics, and the biomedical sector. This research investigated the fabrication and characterization of bioplastics using three types of Honduran agro-wastes: taro, yucca, and banana. The agro-wastes were stabilized and characterized (physicochemically and thermically). Taro flour presented the highest protein content (around 4.7%) and banana flour showed the highest moisture content (around 2%). Furthermore, bioplastics were produced and characterized (mechanically and functionally). Banana bioplastics had the best mechanical properties, with a Young's modulus around 300 MPa, while taro bioplastics had the highest water-uptake capacity (200%). In general, the results showed the potential of these Honduran agro-wastes for producing bioplastics with different characteristics that could add value to these wastes, promoting the circular economy.

Novel Trends in Hydrogel Development for Biomedical Applications: A Review.

Nowadays, there are still numerous challenges for well-known biomedical applications, such as tissue engineering (TE), wound healing and controlled drug delivery, which must be faced and solved. Hydrogels have been proposed as excellent candidates for these applications, as they have promising properties for the mentioned applications, including biocompatibility, biodegradability, great absorption capacity and tunable mechanical properties. However, depending on the material or the manufacturing method, the resulting hydrogel may not be up to the specific task for which it is designed, thus there are different approaches proposed to enhance hydrogel performance for the requirements of the application in question. The main purpose of this review article was to summarize the most recent trends of hydrogel technology, going through the most used polymeric materials and the most popular hydrogel synthesis methods in recent years, including different strategies of enhancing hydrogels' properties, such as cross-linking and the manufacture of composite hydrogels. In addition, the secondary objective of this review was to briefly discuss other novel applications of hydrogels that have been proposed in the past few years which have drawn a lot of attention.

Green Synthesis of FexOy Nanoparticles with Potential Antioxidant Properties.

Iron oxide nanoparticles (FexOy-NPs) are currently being applied in numerous high-tech sectors, such as in chemical sectors for catalysis and in the medical sector for drug delivery systems and antimicrobial purposes, due to their specific, unique and magnetic properties. Nevertheless, their synthesis is under continuous investigation, as physicochemical methods are considered expensive and require toxic solvents. Thus, green nanotechnology has shown considerable promise in the eco-biogenesis of nanoparticles. In the current study, FexOy-NPs were synthesized by two different methods: via green synthesis through the use of polyphenols, which were extracted from Phoenix dactylifera L.; and via chemical synthesis, in which the reducing agent was a chemical (NaOH), and iron chloride was used as a precursor. Thus, polyphenol extraction and its ability to produce nanoparticles were evaluated based on the drying temperature used during the Phoenix dactylifera L. recollection, as well as the extraction solvent used. The results highlight the potential of polyphenols present in Phoenix dactylifera L. for the sustainable manufacture of FexOy-NPs. Finally, green and chemical syntheses were compared on the basis of physicochemical characteristics and functional properties.

Effect of Solution Properties in the Development of Cellulose Derivative Nanostructures Processed via Electrospinning.

In the last few years, electrospinning has proved to be one of the best methods for obtaining membranes of a micro and nanometric fiber size. This method mainly consists in the spinning of a polymeric or biopolymeric solution in solvents, promoted by the difference in the electric field between the needle and collector, which is finally deposited as a conjunction of randomly oriented fibers. The present work focuses on using cellulose derivatives (namely cellulose acetate and ethylcellulose), based on the revaluation of these byproducts and waste products of biorefinery, to produce nanostructured nanofiber through electrospinning with the objective of establishing a relation between the initial solutions and the nanostructures obtained. In this sense, a complete characterization of the biopolymeric solutions (physicochemical and rheological properties) and the resulting nanostructures (microstructural and thermal properties) was carried out. Therefore, solutions with different concentrations (5, 10, 15, and 20 wt%) of the two cellulose derivatives and different solvents with several proportions between them were used to establish their influence on the properties of the resulting nanostructures. The results show that the solutions with 10 wt% in acetic acid/H2O and 15 wt% in acetone/N,N-dimethylformamide of cellulose acetate and 5 wt% of ethylcellulose in acetone/N,N-dimethylformamide, exhibited the best properties, both in the solution and nanostructure state.

Biocompatible and Thermoresistant Hydrogels Based on Collagen and Chitosan.

Hydrogels are considered good biomaterials for soft tissue regeneration. In this sense, collagen is the most used raw material to develop hydrogels, due to its high biocompatibility. However, its low mechanical resistance, thermal stability and pH instability have generated the need to look for alternatives to its use. In this sense, the combination of collagen with another raw material (i.e., polysaccharides) can improve the final properties of hydrogels. For this reason, the main objective of this work was the development of hydrogels based on collagen and chitosan. The mechanical, thermal and microstructural properties of the hydrogels formed with different ratios of collagen/chitosan (100/0, 75/25, 50/50, 25/75 and 0/100) were evaluated after being processed by two variants of a protocol consisting in two stages: a pH change towards pH 7 and a temperature drop towards 4 °C. The main results showed that depending on the protocol, the physicochemical and microstructural properties of the hybrid hydrogels were similar to the unitary system depending on the stage carried out in first place, obtaining FTIR peaks with similar intensity or a more porous structure when chitosan was first gelled, instead of collagen. As a conclusion, the synergy between collagen and chitosan improved the properties of the hydrogels, showing good thermomechanical properties and cell viability to be used as potential biomaterials for Tissue Engineering.

(Macro)Molecular Imprinting of Proteins on PCL Electrospun Scaffolds.

Biological recognition sites are very useful for biomedical purposes and, more specifically, for polymeric scaffolds. However, synthetic polymers are not capable of providing specific biological recognition sites. To solve this inconvenience, functionalization of biological moieties is typically performed, oftentimes via peptide binding. In this sense, the main task is capturing the biological complexity of a protein. This study proposes a possible alternative solution to this challenge. Our approach is based on the combination of molecular imprinting (MI) and electrospinning processes. We propose here an alternative MI approach with polymeric structures, instead of using cross-linkers and monomers as conventionally performed. Different PCL-protein scaffolds were produced via electrospinning before performing MI. Gelatin, collagen, and elastin were used as proteins. Results evidenced that the MI process conducted with PCL electrospun membranes was carried out with ionic interactions between the desired molecules and the recognition sites formed. In addition, it has been proved that MI was more efficient when using gelatin as a template. This approach opens a new stage in the development of recognition sites in scaffolds obtained with synthetic polymers and their application for biomedical purposes.

Applied Rheology as Tool for the Assessment of Chitosan Hydrogels for Regenerative Medicine.

The regeneration of soft tissues that connect, support or surround other tissues is of great interest. In this sense, hydrogels have great potential as scaffolds for their regeneration. Among the different raw materials, chitosan stands out for being highly biocompatible, which, together with its biodegradability and structure, makes it a great alternative for the manufacture of hydrogels. Therefore, the aim of this work was to develop and characterize chitosan hydrogels. To this end, the most important parameters of their processing, i.e., agitation time, pH, gelation temperature and concentration of the biopolymer used were rheologically evaluated. The results show that the agitation time does not have a significant influence on hydrogels, whereas a change in pH (from 3.2 to 7) is a key factor for their formation. Furthermore, a low gelation temperature (4 °C) favors the formation of the hydrogel, showing better mechanical properties. Finally, there is a percentage of biopolymer saturation, from which the properties of the hydrogels are not further improved (1.5 wt.%). This work addresses the development of hydrogels with high thermal resistance, which allows their use as scaffolds without damaging their mechanical properties.

Incorporation of Elastin to Improve Polycaprolactone-Based Scaffolds for Skeletal Muscle via Electrospinning.

Skeletal muscle regeneration is increasingly necessary, which is reflected in the increasing number of studies that are focused on improving the scaffolds used for such regeneration, as well as the incubation protocol. The main objective of this work was to improve the characteristics of polycaprolactone (PCL) scaffolds by incorporating elastin to achieve better cell proliferation and biocompatibility. In addition, two cell incubation protocols (with and without dynamic mechanical stimulation) were evaluated to improve the activity and functionality yields of the regenerated cells. The results indicate that the incorporation of elastin generates aligned and more hydrophilic scaffolds with smaller fiber size. In addition, the mechanical properties of the resulting scaffolds make them adequate for use in both bioreactors and patients. All these characteristics increase the biocompatibility of these systems, generating a better interconnection with the tissue. However, due to the low maturation achieved in biological tests, no differences could be found between the incubation with and without dynamic mechanical stimulation.

Rheological and Microstructural Evaluation of Collagen-Based Scaffolds Crosslinked with Fructose.

In recent years, tissue engineering research has led to the development of this field by designing scaffolds with better properties that can fulfill its purpose of better and faster tissue regeneration, consequently improving people's quality of life. Scaffolds are matrices, predominantly composed of polymeric materials, whose main function is to offer support for cell adhesion and subsequent growth, leading to the regeneration of the damaged tissue. The widely used biopolymer in tissue engineering is collagen, which is the most abundant protein in animals. Its use is due to its structure, biocompatibility, ease of modification, and processability. In this work, collagen-based scaffolds were developed with different concentrations and processing techniques, by obtaining hydrogels and aerogels that were characterized with an emphasis on their morphology and mechanical properties. Moreover, fructose was added in some cases as a chemical crosslinking agent to study its influence on the scaffolds' properties. The obtained results revealed that the scaffolds with higher collagen concentrations were more rigid and deformable. Comparing both systems, the aerogels were more rigid, although the hydrogels were more deformable and had higher pore size homogeneity. Fructose addition produced a slight increase in the critical strain, together with an increase in the elastic modulus.