Chemical composition, antioxidant, and antimicrobial activities of six commercial essential oils.

Essential oils (EOs) and their components extracted from medicinal and aromatic plants are used in several areas, such as perfumery and chemical, cosmetic, food, and pharmaceutical industries. Considering the different applications of EOs, this work aimed to screen the composition and the bioactivities properties of the EOs of Foeniculum vulgare, Helichrysum stoechas, Mentha pulegium, Pinus pinaster, Ruta graveolens, and Thymus mastichina. Gas chromatography-mass spectrometry revealed the presence of different compounds in EOs F. vulgare (12), H. stoechas (27), M. pulegium (8), P. pinaster (24), R. graveolens (8), and T. mastichina (16). All the EOs showed antioxidant activity acting through inhibition of lipid peroxidation, while only two EOs (H. stoechas and M. pulegium) scavenged the free radicals of DPPH. Mentha pulegium and T. mastichina EOs showed the strongest antimicrobial activity. Also, the effect on the fibroblast's viability was directly proportional to the EOs concentration, and the highest cytotoxic effect was registered with R. graveolens EO. The present study revealed significant bioactive properties of different EOs, highlighting M. pulegium and T. mastichina EOs to be considered in further studies for potential use in the food and pharmaceutical industries, due to their antioxidant and antimicrobial properties.

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.

"This snack is too small - I'll take a different one": Quantifying 'norm' and 'choice' boundaries to inform effective portion-reduction strategies.

Previous research suggests that portion sizes can be categorised as 'normal' or 'abnormal' and that reduced portions which are still categorised as normal do not promote compensatory responses in intake. However, a critical question remains - will consumers choose a reduced portion product from among standard portion competitors? For the first time, we explore the effects of portion reduction on food choice. Participants (N = 45) categorised 20 different portions (range 40-420 kcal) of five snacks as normal or abnormal (to quantify individual 'norm boundaries' for each food) and rated their desire to eat each snack. Using a 2-alternative forced choice hypothetical task, we then calculated a 'choice boundary' by offering smaller portions of their most-desired snack (range 40-240 kcal) alongside standardised portions (240 kcal) of the less-desired foods. Boundaries were derived using probit analysis (choice boundary mean = 185.8 kcal, SD = 54, norm boundary mean = 127.3 kcal, SD = 49.5) and these deviated significantly (p < .01, d = 0.98, mean difference = 58.0 kcal, SD = 59.1). Critically, this shows that only a small reduction - where the product is still considered normal - can nudge a consumer to select an alternative. Choice boundaries were also affected by differences in desire to eat; when two foods were desired to a similar degree, only minor reductions in the size of the favourite food elicited a switch in choice. Together, these findings indicate that portion reduction can also influence food choice, highlighting the importance of measuring choice boundaries before reformulating commercial products.

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.

The burden of constipation in psychiatric hospitals.

OBJECTIVE: In this study, we aimed to explore the total burden of constipation in our setting by measuring aggregate laxative consumption data and hospital admissions potentially associated with complications of chronic constipation. In addition, we aimed to determine point prevalence of individual laxative use. METHODS: This study was carried out across all public psychiatric hospitals in the Basque Country. First, laxative consumption data was obtained for the period from January 2008 to October 2016. Total laxative use was then calculated as the total number of individual daily defined doses (DDD). Second, we analyzed the number of admissions to any public acute health-care hospitals for constipation complications. Third, a cross prevalence study was performed to estimate the point constipation prevalence on December 2016. RESULTS: A mean consumption of oral laxatives around 1 DDD per stay and 1 enema per 100 stays was found. A total of 192 admissions potentially associated with constipation complications were recorded. At the time of the study, approximately half of admitted patients had at least one laxative prescribed. CONCLUSIONS: Our study highlights the important burden constipation represents in psychiatric inpatients. Although frequently neglected, it can lead to serious adverse clinical consequences.

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.

Thymus zygis Essential Oil: Phytochemical Characterization, Bioactivity Evaluation and Synergistic Effect with Antibiotics against Staphylococcus aureus.

Staphylococcus aureus is a nosocomial bacterium causing different infectious diseases, ranging from skin and soft-tissue infections to more serious and life-threatening infections such as sepsis, meningitis and endocarditis, which may be exacerbated by antibiotic resistance. Plant products may be seen as an alternative as antibacterial agents, namely, against S. aureus. Thus, the aim of this work was to characterize the chemical composition and evaluate the bioactive properties of the T. zygis essential oil (EO), with a focus on antimicrobial activity against S. aureus. Gas chromatography coupled with mass spectrometry was used to assess the chemical composition of the T. zygis EO, and the antioxidant activity was evaluated using the DPPH method and ß-carotene-bleaching assay. The antimicrobial activity against S. aureus strains, the interaction with different antibiotics and the attenuation of this bacterium's virulence were evaluated. The T. zygis EO showed antioxidant activity acting through two different mechanisms and antibacterial activity against S. aureus, with antibiofilm and antihaemolytic properties. This EO also demonstrated synergistic or additive interactions in combination with ampicillin, ciprofloxacin or vancomycin against S. aureus strains and, in some cases, changed the antibiotic-resistance phenotype from resistant to susceptible. Therefore, the present work demonstrates the good bioactive properties of the EO of T. zygis, mainly the antimicrobial activity against S. aureus, revealing its potential to be used as an antibacterial agent.

Silk Sericin: A Promising Sustainable Biomaterial for Biomedical and Pharmaceutical Applications.

Silk is a natural composite fiber composed mainly of hydrophobic fibroin and hydrophilic sericin, produced by the silkworm Bombyx mori. In the textile industry, the cocoons of B. mori are processed into silk fabric, where the sericin is substantially removed and usually discarded in wastewater. This wastewater pollutes the environment and water sources. However, sericin has been recognized as a potential biomaterial due to its biocompatibility, immunocompatibility, biodegradability, anti-inflammatory, antibacterial, antioxidant and photoprotective properties. Moreover, sericin can produce hydrogels, films, sponges, foams, dressings, particles, fibers, etc., for various biomedical and pharmaceutical applications (e.g., tissue engineering, wound healing, drug delivery, cosmetics). Given the severe environmental pollution caused by the disposal of sericin and its beneficial properties, there has been growing interest in upcycling this biomaterial, which could have a strong and positive economic, social and environmental impact.

Oromucosal Alginate Films with Zein Nanoparticles as a Novel Delivery System for Digoxin.

Digoxin is a hydrophobic drug used for the treatment of heart failure that possesses a narrow therapeutic index, which raises safety concerns for toxicity. This is of utmost relevance in specific populations, such as the elderly. This study aimed to demonstrate the potential of the sodium alginate films as buccal drug delivery system containing zein nanoparticles incorporated with digoxin to reduce the number of doses, facilitating the administration with a quick onset of action. The film was prepared using the solvent casting method, whereas nanoparticles by the nanoprecipitation method. The nanoparticles incorporated with digoxin (0.25 mg/mL) exhibited a mean size of 87.20 ± 0.88 nm, a polydispersity index of 0.23 ± 0.00, and a zeta potential of 21.23 ± 0.07 mV. Digoxin was successfully encapsulated into zein nanoparticles with an encapsulation efficiency of 91% (±0.00). Films with/without glycerol and with different concentrations of ethanol were produced. The sodium alginate (SA) films with 10% ethanol demonstrated good performance for swelling (maximum of 1474%) and mechanical properties, with a mean tensile strength of 0.40 ± 0.04 MPa and an elongation at break of 27.85% (±0.58), compatible with drug delivery application into the buccal mucosa. The current study suggests that SA films with digoxin-loaded zein nanoparticles can be an effective alternative to the dosage forms available on the market for digoxin administration.

Hyaluronic acid-Based wound dressings: A review.

Hyaluronic acid (HA), a non-sulfated glycosaminoglycan (GAG), is a major component of skin extracellular matrix (ECM) and it is involved in the inflammatory response, angiogenesis, and tissue regeneration process. Due to the intrinsic properties of HA (such as biocompatibility, biodegradability and hydrophilic character), it has been used to produce different wound dressings, namely sponges, films, hydrogels, and electrospun membranes. Herein, an overview of the different HA-based wound dressings that have been produced so far is provided as well as the future directions regarding the strategies aimed to improve the mechanical stability of HA-based wound dressings, along with the incorporation of biomolecules intended to ameliorate their biological performance during the healing process.

Photocurable Polymeric Blends for Surgical Application.

The preparation of photocrosslinkable bioadhesives synthesized from oligomers of lactic acid and polycaprolactone (PCL), both functionalized with 2-isocyanoethyl acrylate (AOI), were studied. The obtained modified macromers of LA-AOI (mLA) and PCL-AOI (mCL) were chemically characterized by 1H NMR and used to formulate polymeric blends with different mass proportions, 1:1, 1:2 and 2:1, respectively. Subsequently, the produced blends were crosslinked, considering two UV irradiation times: 30 and 120 s. After their production, the thermal and mechanical properties of bioadhesives were assessed, where upon the rheology, gel content, hydrolytic degradation and dynamic contact angles were determined. Furthermore, the cytotoxic profile of bioadhesives was evaluated in contact with human dermal fibroblasts cells, whereas their antibacterial effect was studied monitoring Escherichia coli and S. aureus growth. Overall, flexible and resistant films were obtained, presenting promising features to be used as surgical bioadhesives.

Hyaluronic acid and vitamin E polyethylene glycol succinate functionalized gold-core silica shell nanorods for cancer targeted photothermal therapy.

Gold-core mesoporous silica shell (AuMSS) nanorods unique physicochemical properties makes them versatile and promising nanomedicines for cancer photothermal therapy. Nevertheless, these nanomaterials present a reduced half-life in the blood and poor specificity towards the tumor tissue. Herein, d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and Hyaluronic Acid (HA) were combined for the first time to improve the AuMSS nanorods biological performance. The obtained results revealed that AuMSS surface functionalization induced the surface charge neutralization, from -28 ±â€¯10 mV to -3 ±â€¯5 mV and -10 ±â€¯4 mV for AuMSS-TPGS-HA (1:1) and (4:1) formulations, without impacting on nanomaterials' photothermal capacity. Moreover, the AuMSS functionalization improved the nanomaterials hemocompatibility and selectivity towards the cancer cells, particularly in the AuMSS-TPGS-HA (4:1) formulation. Furthermore, both formulations were able to mediate an on-demand photothermal effect, that induced the HeLa cancer cells death, confirming its potential for being applied as targeted multifunctional theragnostic nanomedicines.

Poly (vinyl alcohol)/chitosan layer-by-layer microneedles for cancer chemo-photothermal therapy.

The combination of photothermal and chemo- therapies displays a high potential to increase the efficacy of the cancer treatments or even promote their eradication. In this study, the micromoulding and electrospraying techniques were combined to produce polyvinylpyrrolidone microneedles coated with chitosan and poly (vinyl alcohol) for mediating the delivery of doxorubicin and AuMSS nanorods (Dox@MicroN) to cancer cells. The microneedles' physicochemical characterization demonstrated that the electrospraying technique can be used to produce a layer-by-layer coating consisting of layers of doxorubicin-loaded chitosan and AuMSS enriched poly (vinyl alcohol). Further, the Dox@MicroN patches presented a good photothermal capacity leading to a temperature increase of 12 °C under near-infrared irradiation (808 nm, 1.7 W/cm-2 for 5 min), which in conjugation with the chitosan' pH sensitivity could be used to control the doxorubicin release. Moreover, the microneedles were able to penetrate the tumor-mimicking agarose gel and promote a layer dependent drug release. Additionally, the Dox@MicroN patches' capacity to simultaneously mediate the chemo- and photothermal-therapies rendered a superior cytotoxic effect against the cervical cancer cells. Overall, the Dox@MicroN patches demonstrated to be a simple macroscale delivery device that can be used to mediate the local administration of new drug-photothermal combinations, avoiding all the issues related to the systemic administration of anti-cancer therapeutics.

Injectable in situ forming thermo-responsive graphene based hydrogels for cancer chemo-photothermal therapy and NIR light-enhanced antibacterial applications.

Functionalized graphene oxide (GO) and reduced GO (rGO) based nanomaterials hold a great potential for cancer photothermal therapy. However, their systemic administration has been associated with an accelerated blood clearance and/or with suboptimal tumor uptake. To address these limitations, the local delivery of GO/rGO to the tumor site by 3D matrices arises as a promising strategy. In this work, injectable chitosan-agarose in situ forming thermo-responsive hydrogels incorporating GO (thermogel-GO) or rGO (thermogel-rGO) were prepared for the first time. The hydrogels displayed suitable injectability and gelation time, as well as good physicochemical properties and cytocompatibility. When irradiated with near infrared (NIR) light, the thermogel-rGO produced a 3.8-times higher temperature increase than thermogel-GO, thus decreasing breast cancer cells' viability to 60%. By incorporating an optimized molar ratio of the Doxorubicin:Ibuprofen combination on thermogel-rGO, this formulation mediated a chemo-photothermal effect that further diminished cancer cells' viability to 34%. In addition, the hydrogels' antibacterial activity was further enhanced upon NIR laser irradiation, which is an important feature considering the possible risk of infection at the site of administration. Overall, thermogel-rGO is a promising injectable in situ forming hydrogel for combinatorial chemo-photothermal therapy of breast cancer cells and NIR light enhanced antibacterial applications.