Chemical Composition of Macroalgae Polysaccharides from Galician and Portugal Coasts: Seasonal Variations and Biological Properties.

Crude polysaccharides extracted from the Codium sp. and Osmundea sp. macroalgae collected in different seasons (winter, spring and summer) from the Galician and North Portugal coasts were characterised, aiming to support their biomedical application to wound healing. An increase in polysaccharides' sulphate content was registered from winter to summer, and higher values were obtained for Osmundea sp. In turn, the monosaccharide composition constantly changed with a decrease in glucose in Osmundea sp. from spring to winter. For Codium sp., a higher increase was noticed regarding glucose content in the Galician and Portugal coasts. Galactose was the major monosaccharide in all the samples, remaining stable in all seasons and collection sites. These results corroborate the sulphate content and antioxidant activity, since the Osmundea sp.-derived polysaccharides collected in summer exhibited higher scavenging radical ability. The biocompatibility and wound scratch assays revealed that the Osmundea sp. polysaccharide extracted from the Portugal coast in summer possessed more potential for promoting fibroblast migration. This study on seasonal variations of polysaccharides, sulphate content, monosaccharide composition and, consequently, biological properties provides practical guidance for determining the optimal season for algae harvest to standardise preparations of polysaccharides for the biomedical field.

Microneedle-based delivery devices for cancer therapy: A review.

Macroscale delivery systems that can be locally implanted on the tumor tissue as well as avoid all the complications associated to the systemic delivery of therapeutics have captured researchers' attention, in recent years. Particularly, the microneedle-based devices can be used to efficiently deliver both small and macro-molecules, like chemotherapeutics, proteins, and genetic material, along with nanoparticle-based anticancer therapies. Such capacity prompted the application of microneedle devices for the development of new anticancer vaccines that can permeate the tumor tissue and simultaneously improve the effectiveness of therapeutic agents. Based on the promising results demonstrated by the microneedle systems in the local administration of anticancer therapeutics, this review summarizes the different microneedle formulations developed up to now aimed for application on cancer therapy (mphasizing those produced with polymers). Additionally, the microneedles' general properties, type of therapeutic approach and its main advantages are also highlighted.

Recent advances in microalgae encapsulation techniques for biomedical applications.

Microalgae are microorganisms that are rich in bioactive compounds, including pigments, proteins, lipids, and polysaccharides. These compounds can be utilized for a number of biomedical purposes, including drug delivery, wound healing, and tissue engineering. Nevertheless, encapsulating microalgae cells and microalgae bioactive metabolites is vital to protect them and prevent premature degradation. This also enables the development of intelligent controlled release strategies for the bioactive compounds. This review outlines the most employed encapsulation techniques for microalgae, with a particular focus on their biomedical applications. These include ionic gelation, oil-in-water emulsions, and spray drying. Such techniques have been widely explored, due to their ability to protect sensitive compounds from degradation, enhance their stability, extend their shelf life, mask undesirable tastes or odours, control the release of bioactive compounds, and enable targeted delivery to specific sites within the body or environment. Moreover, a patent landscape analysis is also provided, allowing an overview of the microalgae encapsulation technology development applied to a variety of fields, including pharmaceuticals, cosmetics, food, and agriculture.

Interaction of Near-Infrared (NIR)-Light Responsive Probes with Lipid Membranes: A Combined Simulation and Experimental Study.

Cancer is considered a major societal challenge for the next decade worldwide. Developing strategies for simultaneous diagnosis and treatment has been considered a promising tool for fighting cancer. For this, the development of nanomaterials incorporating prototypic near-infrared (NIR)-light responsive probes, such as heptamethine cyanines, has been showing very promising results. The heptamethine cyanine-incorporating nanomaterials can be used for a tumor's visualization and, upon interaction with NIR light, can also produce a photothermal/photodynamic effect with a high spatio-temporal resolution and minimal side effects, leading to an improved therapeutic outcome. In this work, we studied the interaction of 12 NIR-light responsive probes with lipid membrane models by molecular dynamics simulations. We performed a detailed characterization of the location, orientation, and local perturbation effects of these molecules on the lipid bilayer. Based on this information, the probes were divided into two groups, predicting a lower and higher perturbation of the lipid bilayer. From each group, one molecule was selected for testing in a membrane leakage assay. The experimental data validate the hypothesis that molecules with charged substituents, which function as two polar anchors for the aqueous phase while spanning the membrane thickness, are more likely to disturb the membrane by the formation of defects and pores, increasing the membrane leakage. The obtained results are expected to contribute to the selection of the most suitable molecules for the desired application or eventually guiding the design of probe modifications for achieving an optimal interaction with tumor cell membranes.

Three-Dimensionally Printed Hydrogel Cardiac Patch for Infarct Regeneration Based on Natural Polysaccharides.

Myocardial infarction is one of the more common cardiovascular diseases, and remains the leading cause of death, globally. Hydrogels (namely, those using natural polymers) provide a reliable tool for regenerative medicine and have become a promising option for cardiac tissue regeneration due to their hydrophilic character and their structural similarity to the extracellular matrix. Herein, a functional ink based on the natural polysaccharides Gellan gum and Konjac glucomannan has, for the first time, been applied in the production of a 3D printed hydrogel with therapeutic potential, with the goal of being locally implanted in the infarcted area of the heart. Overall, results revealed the excellent printability of the bioink for the development of a stable, porous, biocompatible, and bioactive 3D hydrogel, combining the specific advantages of Gellan gum and Konjac glucomannan with proper mechanical properties, which supports the simplification of the implantation process. In addition, the structure have positive effects on endothelial cells' proliferation and migration that can promote the repair of injured cardiac tissue. The results presented will pave the way for simple, low-cost, and efficient cardiac tissue regeneration using a 3D printed hydrogel cardiac patch with potential for clinical application for myocardial infarction treatment in the near future.

Animal-derived products in science and current alternatives.

More than fifty years after the 3Rs definition and despite the continuous implementation of regulatory measures, animals continue to be widely used in basic research. Their use comprises not only in vivo experiments with animal models, but also the production of a variety of supplements and products of animal origin for cell and tissue culture, cell-based assays, and therapeutics. The animal-derived products most used in basic research are fetal bovine serum (FBS), extracellular matrix proteins such as Matrigel™, and antibodies. However, their production raises several ethical issues regarding animal welfare. Additionally, their biological origin is associated with a high risk of contamination, resulting, frequently, in poor scientific data for clinical translation. These issues support the search for new animal-free products able to replace FBS, Matrigel™, and antibodies in basic research. In addition, in silico methodologies play an important role in the reduction of animal use in research by refining the data previously to in vitro and in vivo experiments. In this review, we depicted the current available animal-free alternatives in in vitro research.

Biopolymers for Tissue Engineering: Crosslinking, Printing Techniques, and Applications.

Currently, tissue engineering has been dedicated to the development of 3D structures through bioprinting techniques that aim to obtain personalized, dynamic, and complex hydrogel 3D structures. Among the different materials used for the fabrication of such structures, proteins and polysaccharides are the main biological compounds (biopolymers) selected for the bioink formulation. These biomaterials obtained from natural sources are commonly compatible with tissues and cells (biocompatibility), friendly with biological digestion processes (biodegradability), and provide specific macromolecular structural and mechanical properties (biomimicry). However, the rheological behaviors of these natural-based bioinks constitute the main challenge of the cell-laden printing process (bioprinting). For this reason, bioprinting usually requires chemical modifications and/or inter-macromolecular crosslinking. In this sense, a comprehensive analysis describing these biopolymers (natural proteins and polysaccharides)-based bioinks, their modifications, and their stimuli-responsive nature is performed. This manuscript is organized into three sections: (1) tissue engineering application, (2) crosslinking, and (3) bioprinting techniques, analyzing the current challenges and strengths of biopolymers in bioprinting. In conclusion, all hydrogels try to resemble extracellular matrix properties for bioprinted structures while maintaining good printability and stability during the printing process.

Osmundea sp. macroalgal polysaccharide-based nanoparticles produced by flash nanocomplexation technique.

The macroalgae-derived polysaccharides' biological potential has been explored due to their attractive intrinsic properties such as biocompatibility, biodegradability, and their ability to conjugate with other compounds. In particular, in the drug delivery systems field, the anionic macroalgae polysaccharides have been combined with cationic compounds through ionotropic gelation and/or bulk mixing. However, these techniques did not assure reproducibility, and the stability of nanoparticles is undesired. To overcome these limitations, herein, the polysaccharide extracted from Osmundea sp. was used to produce nanoparticles through the flash nanocomplexation technique. This approach rapidly mixed the negative charge of macroalgae polysaccharide with a positive chitosan charge on a millisecond timescale. Further, diclofenac (an anti-inflammatory drug) was also incorporated into complex nanoparticles. Overall, the gathered data showed that hydrodynamic diameter nanoparticles values lower than 100 nm, presenting a narrow size distribution and stability. Also, the diclofenac exhibited a targeted and sustained release profile in simulating inflammatory conditions. Likewise, the nanoparticles showed excellent biological properties, evidencing their suitability to be used to treat inflammatory skin diseases.

Single-Step Self-Assembly of Zein-Honey-Chitosan Nanoparticles for Hydrophilic Drug Incorporation by Flash Nanoprecipitation.

Zein- and chitosan-based nanoparticles have been described as promising carrier systems for food, biomedical and pharmaceutical applications. However, the manufacture of size-controlled zein and chitosan particles is challenging. In this study, an adapted anti-solvent nanoprecipitation method was developed. The effects of the concentration of zein and chitosan and the pH of the collection solution on the properties of the zein-honey-chitosan nanoparticles were investigated. Flash nanoprecipitation was demonstrated as a rapid, scalable, single-step method to achieve the self-assembly of zein-honey-chitosan nanoparticles. The nanoparticles size was tuned by varying certain formulation parameters, including the total concentration and ratio of the polymers. The zein-honey-chitosan nanoparticles' hydrodynamic diameter was below 200 nm and the particles were stable for 30 days. Vitamin C was used as a hydrophilic model substance and efficiently encapsulated into these nanoparticles. This study opens a promising pathway for one-step producing zein-honey-chitosan nanoparticles by flash nanoprecipitation for hydrophilic compounds' encapsulation.

Ciprofloxacin-Loaded Zein/Hyaluronic Acid Nanoparticles for Ocular Mucosa Delivery.

Bacterial conjunctivitis is a worldwide problem that, if untreated, can lead to severe complications, such as visual impairment and blindness. Topical administration of ciprofloxacin is one of the most common treatments for this infection; however, topical therapeutic delivery to the eye is quite challenging. To tackle this, nanomedicine presents several advantages compared to conventional ophthalmic dosage forms. Herein, the flash nanoprecipitation technique was applied to produce zein and hyaluronic acid nanoparticles loaded with ciprofloxacin (ZeinCPX_HA NPs). ZeinCPX_HA NPs exhibited a hydrodynamic diameter of <200 nm and polydispersity index of <0.3, suitable for ocular drug delivery. In addition, the freeze-drying of the nanoparticles was achieved by using mannitol as a cryoprotectant, allowing their resuspension in water without modifying the physicochemical properties. Moreover, the biocompatibility of nanoparticles was confirmed by in vitro assays. Furthermore, a high encapsulation efficiency was achieved, and a release profile with an initial burst was followed by a prolonged release of ciprofloxacin up to 24 h. Overall, the obtained results suggest ZeinCPX_HA NPs as an alternative to the common topical dosage forms available on the market to treat conjunctivitis.