Enhancing Alginate Hydrogels as Possible Wound-Healing Patches: The Synergistic Impact of Reduced Graphene Oxide and Tannins on Mechanical and Adhesive Properties.

Hydrogels are three-dimensional crosslinked materials known for their ability to absorb water, exhibit high flexibility, their biodegradability and biocompatibility, and their ability to mimic properties of different tissues in the body. However, their application is limited by inherent deficiencies in their mechanical properties. To address this issue, reduced graphene oxide (rGO) and tannins (TA) were incorporated into alginate hydrogels (Alg) to evaluate the impact of the concentration of these nanomaterials on mechanical and adhesive, as well as cytotoxicity and wound-healing properties. Tensile mechanical tests demonstrated improvements in tensile strength, elastic modulus, and toughness upon the incorporation of rGO and TA. Additionally, the inclusion of these materials allowed for a greater energy dissipation during continuous charge-discharge cycles. However, the samples did not exhibit self-recovery under environmental conditions. Adhesion was evaluated on pig skin, revealing that higher concentrations of rGO led to enhanced adhesion, while the concentration of TA did not significantly affect this property. Moreover, adhesion remained consistent after 10 adhesion cycles, and the contact time before the separation between the material and the surface did not affect this property. The materials were not cytotoxic and promoted healing in human fibroblast-model cells. Thus, an Alg/rGO/TA hydrogel with enhanced mechanical, adhesive, and wound-healing properties was successfully developed.

Enhancing Soil Resilience: Bacterial Alginate Hydrogel vs. Algal Alginate in Mitigating Agricultural Challenges.

Erosion and tillage changes negatively the soil physical structure, which directly impacts agricultural systems and consequently food security. To mitigate these adverse modifications, different polymeric materials from synthetic and natural sources, have been used as soil conditioners to improve the hydro-mechanical behavior of affected soils. One of the most interesting and used natural polymers is the alginate hydrogel. Although commercially available alginate hydrogels are primarily sourced from algal, they can also be sourced from bacteria. The gelation capacity of these hydrogels is determined by their molecular properties, which, in turn, are influenced by the production conditions. Bacterial alginate hydrogel production offers the advantage of precise control over environmental conditions during cultivation and extraction, thereby maintaining and enhancing their molecular properties. This, in turn, results in higher molecular weight and improved gelation capacity. In this study, we compared the effects of bacterial alginate (BH) and algal alginate (AH) hydrogels over the mechanical, hydraulic, and structural behavior of coarse quartz sand as a model soil. Mechanically, it was observed that the treatment with the lowest concentration of bacteria alginate hydrogel (BH1) reached higher values of yield strength, Young's modulus (E), shear modulus (G) and strain energy (U) than those treatments with algal alginate hydrogel (AH). Furthermore, the increase in the aggregate stability could be associated with the improvement of mechanical parameters. On the other hand, a greater water retention capacity was observed in the BH treatments, as well as a greater decrease in hydraulic conductivity with respect to the AH and control treatments. All these changes could be explained by the formation of bridge-like structures between the sand particles and the hydrogel, and this alteration may result in a shift in the mechanical and wettability characteristics of the treated soils. Finally, our findings emphasize the superior impact of bacterial alginate hydrogel on enhancing the mechanical and hydraulic properties of coarse quartz sand compared to traditional algal alginate. Besides, the use of bacterial alginate hydrogel could be useful to counteract erosion and water scarcity scenarios in agricultural systems.

Cytotoxicity and Antibacterial Activity of Alginate Hydrogel Containing Nitric Oxide Donor and Silver Nanoparticles for Topical Applications.

Nitric oxide (NO) and silver nanoparticles (AgNPs) are well-known for their antibacterial activity. In this work, S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), a NO donor, and green tea synthesized AgNPs were individually or simultaneously incorporated into alginate hydrogel for topical antibacterial applications. The obtained hydrogels were characterized and the NO release and diffusion of AgNPs and S-nitroso-MSA from alginate hydrogels were investigated. The hydrogels showed a concentration dependent toxicity toward Vero cells. The potent antibacterial effect of the hydrogels was demonstrated toward Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Streptococcus mutans UA159. Interestingly, the combination of S-nitroso-MSA and AgNPs into alginate hydrogels had a superior antibacterial effect, compared with hydrogels containing S-nitroso-MSA or AgNPs individually. This is the first report to describe the synthesis, cytotoxicity, and antibacterial effects of alginate hydrogel containing NO donor and AgNPs. These hydrogels might find important local applications in the combat of bacterial infections.

Alginate-Based Delivery Systems for Bevacizumab Local Therapy: In Vitro Structural Features and Release Properties.

Alginate-based polyelectrolyte complexes (PECs) and hydrogel were engineered as platforms for local bevacizumab (BVZ) therapy. This study provides deep comprehension on the microstructures of such systems, and their correlation with drug-release patterns. PECs and hydrogel were characterized using Fourier transform infrared spectroscopy, small-angle X-ray scattering, scanning electron microscopy, atomic force microscopy, and porosimetry. Structural investigations indicated that PECs are formed by supramolecular interactions, resulting in physically cross-linked polymer networks, whereas the BVZ-loaded hydrogel has a more compact and rigid structure, promoting better entrapment of BVZ. PECs and hydrogel were able to control the BVZ release for 4 and 8 days, respectively. Their release profiles correlated best with the Higuchi and Korsmeyer-Peppas models, respectively, indicating drug diffusion as the limiting step for drug release. Furthermore, BVZ remained biologically active in vitro after its incorporation into the hydrogel system. Together, these studies confirm that PECs and hydrogel exhibit different porous structures and physicochemical properties, making them promising platforms that allow the modulation of BVZ release meeting different requirements.

Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapy.

Anti-vascular endothelial growth factor (anti-VEGF) therapy applied to solid tumors is a promising strategy, yet, the challenge to deliver these agents at high drug concentrations together with the maintenance of therapeutic doses locally, at the tumor site, minimizes its benefits. To overcome these obstacles, we propose the development of a bevacizumab-loaded alginate hydrogel by electrostatic interactions to design a delivery system for controlled and anti-angiogenic therapy under tumor microenvironmental conditions. The tridimensional hydrogel structure produced provides drug stability and a system able to be introduced as a flowable solution, stablishing a depot after local administration. Biological performance by the chick embryo chorioallantoic membrane (CAM) assay indicated a pH-independent improved anti-angiogenic activity (∼50%) compared to commercial available anti-VEGF drug. Moreover, there was a considerable regression in tumor size when treated with this system. Immunohistochemistry highlighted a reduced number and disorganization of microscopic blood vessels resulting from applied therapy. These results suggest that the developed hydrogel is a promising approach to create an innovative delivery system that offers the possibility to treat different solid tumors by intratumoral administration.

A novel pH-responsive hydrogel-based on calcium alginate engineered by the previous formation of polyelectrolyte complexes (PECs) intended to vaginal administration.

This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation between alginate and PMX followed by crosslinking with calcium chloride. This system exhibited a morphology with variable pore sizes, ranging from 100 to 200 µm and adequate syringeability. The hydrogel liquid uptake ability in an acid environment was minimized by the previous PECs formation. In vitro tests evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the system was able to sustain the release up to 6 days. A burst release was observed at pH 7.4 and drug release was driven by an anomalous transport, as determined by the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model and drug transport was driven by Fickian diffusion. The calcium alginate hydrogels engineered by the previous formation of PECs showed to be a promising platform for sustained release of cationic drugs through vaginal administration.