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The green macroalga Ulva rigida represents a promising feedstock for biorefinary due to its fast growth and cosmopolitan distribution. The main component of the cell walls of U. rigida is a sulfated glucuronorhamnan polysaccharide known as ulvan. Herein it was found that due to the high (hydrogen)sulfate group content of ulvan, hydrothermal autohydrolysis at 130 °C renders a high percentage of rhamnose (78–79 % recovery from the initial content in the raw material), a rare sugar of high added value. In addition, acid catalysis by a triflate-based graphene oxide under oxygen-free conditions at 180 °C affords moderate amounts of tartaric acid (24–26 %). The same triflate-based graphene oxide catalyst under oxygen pressure yields remarkably high percentages of succinic acid (65 %). The catalyst preserves its activity for at least five consecutive reuses., Financial support by the Spanish Ministry of Economy and Competitiveness (Severo Ochoa SEV2016-0683, RTI2018-890237-CO2-R1) and Generalitat Valenciana (Prometeo 2017−083) is gratefully acknowledged. Vasile I. Parvulescu kindly acknowledges UEFISCDI for financial support (project PN-III-P4-ID-PCE-2016-0146, Nr. 121/2017).

Construction of extracellular matrix-mimetic nanofilms has considerable potential in biomedical and nanomedicinal fields. In this work, we fabricated neurocompatible layer-by-layer (LbL) films based on ulvan (ULV), a highly sulfated polysaccharide having compositional similarity to glycosaminoglycans that play important functional roles in the brain. ULV was durably assembled as a film with chitosan, another marine-derived polysaccharide, and the film enabled the stable adhesion of primary hippocampal neurons with high viability, comparable to the conventional poly-d-lysine surface. Notably, the ULV-based LbL films accelerated neurite outgrowth and selectively suppressed the adhesion of astrocytes, highlighting its potential as an advanced platform for neural implants and devices.

Background Mosquitoes are hematophagous insects of major public health concern, serving as vectors of many diseases. Available products for personal protection against mosquitoes lack adequate efficacy and in most cases need to be reapplied or replaced frequently. In recent years, the encapsulation of the active repellents in various matrices has arisen as an alternative method for the development of new-generation repellent systems. The aim of the present study was to explore the potential of functional micro/nanofibrous matrices as systems for the sustained release of the highly volatile insect-repellent citronella oil. Results Micro/nanofibrous single- and triple-layer systems incorporating citronella oil as the active agent were developed via the electrospinning technique using the low-cost, non-toxic, biodegradable polymers cellulose acetate and polyvinylpyrrolidone. All the micro/nanofiber systems produced exhibited prolonged release of citronella oil and a high repellent activity in laboratory bioassays against the mosquito Aedes albopictus for at least 4 weeks. Conclusion Considering the high volatility of the embedded repellent, the present study demonstrates the strong potential of the micro/nanofibrous matrices to act as carriers of highly volatile repellents for an effective and sustained protection from mosquitoes. © 2019 Society of Chemical Industry.

Modified release tablet formulations with melatonin (MLT) are clinically more useful in initiating and maintaining sleep in elderly insomniacs, compared with those designed for immediate release. Aiming at the modified release of MLT, monolayered and 3-layered tablets, incorporating nanofibrous mats composed of cellulose acetate and polyvinylpyrrolidone loaded with MLT, were prepared and studied. In vitro dissolution profiles of MLT in gastrointestinal-like fluids revealed tableting pressure/pH-dependence. The release of the hormone from physical mixture tablets was generally slower from the nanofibers-based tablets, thus exhibiting in the latter case properties that are necessary for the control of both the sleep-onset and the maintenance dysfunctions. The nature of the excipients (hydroxypropylmethylcellulose or lactose monohydrate) used in this study to produce 3-layered tablets was also found to affect the release of MLT, adjusting it to the endogenous hormone's chronobiotic profile. The release of MLT from formulation F(nf)2 (nanofiber mats incorporated into 3-layered tablets containing lactose monohydrate both in the upper and lower layers) was found to be in closer alignment with these effects than the other delivery systems.

Acute radiodermatitis is the most common side effect in non-melanoma skin cancer patients undergoing radiotherapy. Nonetheless, despite the ongoing progress of clinical trials, no effective regimen has been found yet. In this study, a non-woven patch, comprised of electrospun polymeric micro/nanofibers loaded with an aqueous extract of Pinus halepensis bark (PHBE), was fabricated and clinically tested for its efficacy to prevent radiodermatitis. The bioactivity of the PHBE patch was evaluated in comparison with a medical cream indicated for acute radiodermatitis. Twelve volunteer patients were selected and randomly assigned to two groups, applying either the PHBE patch or the reference cream daily. Evaluation of radiation-induced skin reactions was performed during the radiotherapy period and 1 month afterwards according to the Radiation Therapy Oncology Group (RTOG) grading scale, photo-documentation, patient-reported outcomes (Visual Analog Scale, questionnaire), biophysical measurements (hydration, transepidermal water loss, erythema, melanin), and image analysis. In contrast with the reference product, the PHBE patch showed significant anti-inflammatory activity and restored most skin parameters to normal levels 1 month after completion of radiation therapy. No adverse event was reported, indicating that the application of the PHBE patch can be considered as a safe medical device for prophylactic radiodermatitis treatment.

Nisin is an attractive alternative to chemical preservatives in the food industry. It is a cationic peptide of 34 amino acid residues that exhibits antimicrobial activity against Gram-positive bacteria. To ensure nisin stability in food matrices, new nisin-loaded ulvan particles were developed by the complexation method. The interaction of nisin with ulvan was demonstrated by FT-IR spectroscopy and differential scanning calorimetry. The encapsulation efficiency was calculated at different pH values within the range of 4.0–7.0 and was found to have the highest value at pH 7.0. The size and surface charge of particles fabricated at different concentrations of nisin and pH values were determined. Nisin-loaded ulvan particles exhibited antimicrobial activity against Gram-positive bacteria comparable to that of free nisin. Therefore, the developed complexes have the potential for application as biopreservatives in the food industry. For the first time, the potential of ulvan as a carrier of antimicrobial agent nisin was demonstrated.

Simple Summary The most frequent adverse effect for patients receiving radiotherapy, an effective treatment for skin cancer when surgical removal of the tumor is impossible, is acute radiodermatitis, affecting patients’ physical function and often leading to therapy termination. Creams and other topical formulations used so far for the prevention of acute radiodermatitis are applied at regular intervals but do not ensure a constant and controlled transepidermal absorption. The aqueous extract of Aleppo pine bark, previously preclinically and clinically assessed in the form of gel, was herein loaded on micro/nanofibrous patches and clinically evaluated in comparison with a commercially used reference cream on non-melanoma skin carcinoma patients undergoing radiotherapy. The experimental patch significantly contributed to prophylaxis and successful management of acute radiodermatitis, safely restoring skin and its biophysical parameters to normal levels and reducing patients’ discomfort. Topical application of pine-loaded micro/nanofibrous patches holds great potential for the development of a new generation of anti-inflammatory skin care dressings against radiodermatitis. Abstract Acute radiodermatitis is the most common side effect in non-melanoma skin cancer patients undergoing radiotherapy. Nonetheless, despite the ongoing progress of clinical trials, no effective regimen has been found yet. In this study, a non-woven patch, comprised of electrospun polymeric micro/nanofibers loaded with an aqueous extract of Pinus halepensis bark (PHBE), was fabricated and clinically tested for its efficacy to prevent radiodermatitis. The bioactivity of the PHBE patch was evaluated in comparison with a medical cream indicated for acute radiodermatitis. Twelve volunteer patients were selected and randomly assigned to two groups, applying either the PHBE patch or the reference cream daily. Evaluation of radiation-induced skin reactions was performed during the radiotherapy period and 1 month afterwards according to the Radiation Therapy Oncology Group (RTOG) grading scale, photo-documentation, patient-reported outcomes (Visual Analog Scale, questionnaire), biophysical measurements (hydration, transepidermal water loss, erythema, melanin), and image analysis. In contrast with the reference product, the PHBE patch showed significant anti-inflammatory activity and restored most skin parameters to normal levels 1 month after completion of radiation therapy. No adverse event was reported, indicating that the application of the PHBE patch can be considered as a safe medical device for prophylactic radiodermatitis treatment.

Hybrid composites of synthetic and natural polymers represent materials of choice for bone tissue engineering. Ulvan, a biologically active marine sulfated polysaccharide, is attracting great interest in the development of novel biomedical scaffolds due to recent reports on its osteoinductive properties. Herein, a series of hybrid polycaprolactone scaffolds containing ulvan either alone or in blends with κ-carrageenan and chondroitin sulfate was prepared and characterized. The impact of the preparation methodology and the polysaccharide composition on their morphology, as well as on their mechanical, thermal, water uptake and porosity properties was determined, while their osteoinductive potential was investigated through the evaluation of cell adhesion, viability, and osteogenic differentiation of seeded human adipose-derived mesenchymal stem cells. The results verified the osteoinductive ability of ulvan, showing that its incorporation into the polycaprolactone matrix efficiently promoted cell attachment and viability, thus confirming its potential in the development of biomedical scaffolds for bone tissue regeneration applications.

Ulvan, a bioactive natural sulfated polysaccharide, and gelatin, a collagen-derived biopolymer, have attracted interest for the preparation of biomaterials for different biomedical applications, due to their demonstrated compatibility for cell attachment and proliferation. Both ulvan and gelatin have exhibited osteoinductive potential, either alone or in combination with other materials. In the current work, a series of novel hybrid scaffolds based on crosslinked ulvan and gelatin was designed, prepared and characterized. Their mechanical performance, thermal stability, porosity, water-uptake and in vitro degradation ability were assessed, while their morphology was analyzed through scanning electron microscopy. The prepared hybrid ulvan/gelatin scaffolds were characterized by a highly porous and interconnected structure. Human adipose-derived mesenchymal stem cells (hADMSCs) were seeded in selected ulvan/gelatin hybrid scaffolds and their adhesion, survival, proliferation, and osteogenic differentiation efficiency was evaluated. Overall, it was found that the prepared hybrid sponge-like scaffolds could efficiently support mesenchymal stem cells&rsquo, adhesion and proliferation, suggesting that such scaffolds could have potential uses in bone tissue engineering.

In the last decades the paradigm of including excipients in the formulations as inert substances, aiding production processes, has changed and they are now approached as multifunctional compounds. This means that several functions apply, spreading from the stabilization and modified release, to providing biocompatible properties and targeting moieties. In the present work, the algal sulfated polysaccharide ulvan, which remains a rather unexploited biomaterial for applications in the design of drug delivery systems, was used as a formulant in hydrophilic matrix systems, containing the chronobiotic hormone melatonin (MLT). The MLT's in vitro modified release profile in gastrointestinal-like fluids was probed. In general, the % release profile of MLT from ulvan-based tablets, was found to be relatively higher than that of the market drug Circadin® at pH 1.2 (2 h), with the exception of the formulations containing HPMC K15M. The release of most of the ulvan-based formulations follow a sigmoidal pattern (Super Case II mechanism, n > 0.89), which denotes that the drug release is controlled by polymer relaxation and/or erosion.

The aim of the present study was the encapsulation of Rosmarinus officinalis essential oil (REO) in β-cyclοdextrin (β-CD) and two chemically modified β-CD matrices and the evaluation of the antibacterial activity of the prepared inclusion complexes against Staphylococcus aureus. The inclusion complexes possessed nanoscale size ranging from 395.7 ± 13.7 to 594.9 ± 18.8 nm, good size dispersion (0.366 ± 0.009 to 0.482 ± 0.043) and satisfactory stability in suspension (ζ-potential, −24.3 ± 4.2 to −31.5 ± 4.9 mV), while the inclusion efficiency ranged from 65% to 78%. The in vitro release profiles of the inclusion complexes revealed an initial burst effect, with the release kinetics being better fitted on the Higuchi model following quasi-Fickian diffusion. The antibacterial activity of the inclusion complexes of REO in β-CD, HP-β-CD and Me-β-CD against S. aureus was evaluated for 3 days and it was observed that both β-CD and HP-β-CD exhibited prolonged activity in comparison to the pure REO.

New systems for the controlled release of 1,7-dioxaspiro[5.5]undecane and (Z)-7-tetradecenal, the sex pheromones of olive fruit fly, Bactrocera oleae, and olive moth, Prays oleae, respectively, were developed utilizing electrospun micro/nanofiber matrices from inexpensive, biodegradable polymers, namely polycaprolactone, cellulose acetate and polyhydroxybutyrate. The incorporation of the pheromones in 5, 10 and 20% w/w in the electrospinning polymer blends allowed for the production of fiber mats with variable loading levels and release rates, ensuring however in all cases the release of pheromones for more than 16 weeks. Laboratory bioassays and field trapping tests showed that the fiber mats obtained from electrospinning of polyhydroxybutyrate solution containing 5% w/w 1,7-dioxaspiro[5.5]undecane and polycaprolactone solution containing 5% w/w (Z)-7-tetradecenal were almost twice as effective in attracting B. oleae and P. oleae males, respectively, in comparison to the positive controls used.

Skin inflammation is the most common symptom in dermatological diseases. It is usually treated by topically applied products, such as creams, gels and lotions. Skin dressings offer a promising alternative as they are endowed with more controlled administration conditions. In this study, the anti-inflammatory activity of electrospun alginate micro/nanofibrous dressings loaded with the aqueous extract of Pinus halepensis bark (PHBE) was evaluated in vivo in mice. The upper back skin of SKH-1 female hairless mice was exposed to a single dose of ultraviolet radiation (3 MEDs) and the inflamed area was treated daily by the direct application of a nanofibrous patch. The condition of the skin was evaluated primarily on the basis of clinical observation, photo-documentation and histopathological assessment, while measurements of the erythema, hydration, transepidermal water loss (TEWL) and sebum production were also taken into account. The results showed that the topical application of alginate micro/nanofibrous dressings loaded with PHBE on UV-inflamed skin significantly attenuated inflammation damage, reducing the healing period. Increase of the loading dose of PHBE resulted in a proportional reduction of the extent, the density and the depth of skin inflammation. With the steadily increasing interest of the skin dressing industry towards nanofibrous matrices, electrospun nonwovens could serve as ideal candidates for the development of multifunctional anti-inflammatory care systems.

Inflammation is part of the organism&rsquo, s response to deleterious stimuli, such as pathogens, damaged cells, or irritants. Macrophages orchestrate the inflammatory response obtaining different activation phenotypes broadly defined as M1 (pro-inflammatory) or M2 (homeostatic) phenotypes, which contribute to pathogen elimination or disease pathogenesis. The type and magnitude of the response of macrophages are shaped by endogenous and exogenous factors and can be affected by nutrients or therapeutic agents. Multiple studies have shown that natural products possess immunomodulatory properties and that marine algae contain products with such action. We have previously shown that disulfides isolated from Dictyopteris membranacea suppress nitric oxide (NO) production from activated macrophages, suggesting potential anti-inflammatory actions. In this study, we investigated the anti-inflammatory mechanism of action of bis(5-methylthio-3-oxo-undecyl) disulfide (1), 5-methylthio-1-(3-oxo-undecyl) disulfanylundecan-3-one (2) and 3-hexyl-4,5-dithiocycloheptanone (3). Our results showed that all three compounds inhibited M1 activation of macrophages by down regulating the production of pro-inflammatory cytokines TNF&alpha, IL-6 and IL-12, suppressed the expression of the NO converting enzyme iNOS, and enhanced expression of the M2 activation markers Arginase1 and MRC1. Moreover, disulfides 1 and 2 suppressed the expression of glucose transporters GLUT1 and GLUT3, suggesting that compounds 1 and 2 may affect cell metabolism. We showed that this was due to AKT/MAPK/ERK signaling pathway modulation and specifically by elevated AKT phosphorylation and MAPK/ERK signal transduction reduction. Hence, disulfides 1&ndash, 3 can be considered as potent candidates for the development of novel anti-inflammatory molecules with homeostatic properties.

Mosquitoes are hematophagous insects of major public health concern, serving as vectors of many diseases. Available products for personal protection against mosquitoes lack adequate efficacy and in most cases need to be reapplied or replaced frequently. In recent years, the encapsulation of the active repellents in various matrices has arisen as an alternative method for the development of new-generation repellent systems. The aim of the present study was to explore the potential of functional micro/nanofibrous matrices as systems for the sustained release of the highly volatile insect-repellent citronella oil.Micro/nanofibrous single- and triple-layer systems incorporating citronella oil as the active agent were developed via the electrospinning technique using the low-cost, non-toxic, biodegradable polymers cellulose acetate and polyvinylpyrrolidone. All the micro/nanofiber systems produced exhibited prolonged release of citronella oil and a high repellent activity in laboratory bioassays against the mosquito Aedes albopictus for at least 4 weeks.Considering the high volatility of the embedded repellent, the present study demonstrates the strong potential of the micro/nanofibrous matrices to act as carriers of highly volatile repellents for an effective and sustained protection from mosquitoes. © 2019 Society of Chemical Industry.

Objective: Aiming at the modified release of melatonin (MLT), electrospun-MLT loaded nanofibers, filled into hard gelatin and DRcapsTM capsules, were used as formulants. Methods: Cellulose acetate, polyvinylpyrrolidinone and hydroxypropylmethylcellusose (HPMC 2910) were used for the preparation of the fiber matrices through electrospinning. The in vitro modified release profile of MLT from the fabricated matrices in gastrointestinal-like fluids was studied. At pH 1.2, the formulations CA1, CA2, PV1, HP1, HP2 and the composite formulations CAPV1-CAPV5 in hard gelatin capsules exhibited fast MLT release. Results: In general, the same trend was observed at pH 6.8, with the exception of CAPV1 and CAPV2. These two composite formulations delivered 52.08% and 75.25% MLT, respectively at a slower pace (6 h) when encapsulated in DRcapsTM capsules. In all other cases, the release of MLT from DRcapsTM capsules filled with the MLT-loaded nanofibers reached 100% at 6h. Conclusion: These findings suggest that the MLT-loaded nanofibrous mats developed in this study exhibit a promising profile for treating sleep dysfunctions.

The aim of the present work was to study the encapsulation of Origanum onites L. essential oil (oregano EO) in β-cyclodextrin (β-CD) inclusion complexes (ICs), using the co-precipitation method. The formed β-CD–oregano EO ICs were characterized by diverse methods, such as Dynamic Light Scattering (DLS), FT-IR spectroscopy, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning Electron Microscopy (SEM). UV-Vis spectroscopy was used for the determination of the inclusion efficacy and the study of the encapsulated oregano EO release profile. The interactions between host (β-CD) and guest (oregano EO) in the formed ICs were proven by the FT-IR, DSC, TG and NMR analyses. The ICs, which derived from different batches, presented nanoscale size (531.8 ± 7.7 nm and 450.3 ± 11.5 nm, respectively), good size dispersion (0.308 ± 0.062 and 0.484 ± 0.029, respectively) and satisfactory stability in suspension (ζ-potential = −21.5 ± 1.2 mV and −30.7 ± 1.8 mV). Inclusion efficiency reached up to 26%, whereas the oregano EO release from the ICs followed a continuous delivery profile for up to 11 days, based on in vitro experiments. The formed ICs can find diverse applications, such as in the preparation of films for active packaging of food products, in personal care products for the improvement of their properties (e.g., antioxidant, antimicrobial, etc.), as well as in insect repellent products.

Furosemide, a chloride channel blocker ordinarily used as a high-ceiling or loop diuretic, is practically insoluble in water and dilute acids. Due to its acidic nature, furosemide is mostly absorbed in the stomach and in the upper small intestine. Efforts have focused on the development of sustained release systems of furosemide in order to improve the effectiveness of the drug, which exhibits poor aqueous solubility and poor permeability. Recently, electrospun nanofibrous drug delivery systems have emerged as promising alternative solid-dosage forms due to their advantages of high porosity, high surface to volume ratio, and high drug-loading efficacy. Herein, a number of nanofibrous mats composed of different types of Eudragit&reg, polymers in various concentrations and combinations loaded with furosemide were designed, successfully electrospun, and characterized using SEM, FTIR, DSC, and TGA analyses. The nanofibrous nonwovens were formulated in nanofiber tablets and the release profile of furosemide from them was evaluated at pH 1.2 and 6.8 and compared to that of physical mixture matrix tablets of analogous composition as well as to that of a commercial formulation. It was found that the release of furosemide was compatible with the gastroretentive and slower intestinal release requirements with a well-defined absorption window, while some nanofiber formulations could act as furosemide carriers in emergency situations where a relatively fast onset of its action is required, as in the case of critically ill post-traumatic patients.

In the present study, the heartwood and the sapwood of a thick wood disc from a dated Cedrus brevifolia trunk, and the resin were analyzed for their volatile components. All samples were subjected to headspace solid-phase microextraction followed by gas chromatography mass spectrometry analysis. The main constituents were β-himachalene (22.2 %) in heartwood and (25.0 %) in sapwood, and α-pinene (37.8 %) in resin.

Novel and promising thiophenone derivatives were synthesised by regioselective ring opening of activated thiomalic acid anhydrides, with a variety of active methylene nucleophiles via a C-acylation/cyclisation process involving an S–C bond formation. This regioselective approach could be moreover established by X-ray diffraction structure analysis. The thiolactone ring can act as valuable synthetic scaffold for the preparation of natural and synthetic compounds with important biological and pharmacological activities.

A novel short-step methodology to benzothiopyranone derivatives has been developed starting from an activated precursor, N-hydroxysuccinimide ester of thiosalicylic acid. The procedure is based on a tandem C-acylation–cyclisation process under mild reaction conditions in good yields. The structure elucidation has been established using X-ray crystallography and NMR spectral data.

Novel fibrous biocomposites comprising ulvan, a sulfated polysaccharide extracted from the green seaweed Ulva rigida, and either polycaprolactone or polyethylene oxide were successfully prepared using the electrospinning technique. The morphology and the chemical composition of the nanofibers were characterized using SEM and FT-IR analyses. Ulvan was found to incorporate well with the co-electrospun biocompatible polymers, conferring on the collective properties of these materials. Such nanofibrous matrices represent potentially useful materials in the biomedical sector as tissue engineering scaffolds, wound dressings, or drug delivery systems. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42153.

The thiotetronic ring system is the key intermediate for the synthetic approach to thiolactomycin analogues. A novel one-pot synthesis of the thiotetronic ring system is described. The proposed methodology is based on a C-acylation/cyclization reaction between the N-hydroxysuccinimide esters of S-acetyl-thioglycolic acids and the appropriate active methylene compounds. 1 H and 13 C NMR spectroscopic data for the synthesized thiotetronic acids and 2-aminothiophenones are presented.

Dendritic-linear-dendritic (DLD) hybrids are highly functional materials combining the properties of linear and dendritic polymers. Attempts to electrospin DLD polymers composed of hyperbranched dendritic blocks of 2,2-bis(hydroxymethyl) propionic acid on a linear poly(ethylene glycol) core proved unsuccessful. Nevertheless, when these DLD hybrids were blended with an array of different biodegradable polymers as entanglement enhancers, nanofibrous nonwovens were successfully prepared by electrospinning. The pseudogeneration degree of the DLDs, the nature of the co-electrospun polymer and the solvent systems used for the preparation of the electrospinning solutions exerted a significant effect on the diameter and morphology of the electrospun fibers. It is worth-noting that aqueous solutions of the DLD polymers and only 1% (w/v) poly(ethylene oxide) resulted in the production of smoother and thinner nanofibers. Such dendritic nanofibrous scaffolds can be promising materials for biomedical applications due to their biocompatibility, biodegradability, multifunctionality, and advanced structural architecture. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 135, 45949.

Tetronic acids, 4-hydroxy-5H-furan-2-ones, constitute a class of heterocyclic compounds with potent biological and pharmacological activity. Theβ,β′-tricarbonyl moiety plays an integral role in biological systems and forms a variety of metal complexes. In this report, we present the complexation reactions of 3-ethoxycarbonyl tetronic acids with acetates and chlorides of Cu(II) and Co(II). These complexes have been studied by means of EPR spectroscopy and magnetic susceptibility measurements. From the obtained results, a preliminary complexation mode of the ligand is proposed.