Advanced Nanocellulose-Based Materials: Production, Properties and Applications

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The role of ionic liquids in the pharmaceutical field: an overview of relevant applications

Solubility, bioavailability, permeation, polymorphism, and stability concerns associated to solid-state pharmaceuticals demand for effective solutions. To overcome some of these drawbacks, ionic liquids (ILs) have been investigated as solvents, reagents, and anti-solvents in the synthesis and crystallization of active pharmaceutical ingredients (APIs), as solvents, co-solvents and emulsifiers in drug formulations, as pharmaceuticals (API-ILs) aiming liquid therapeutics, and in the development and/or improvement of drug-delivery-based systems. The present review focuses on the use of ILs in the pharmaceutical field, covering their multiple applications from pharmaceutical synthesis to drug delivery. The most relevant research conducted up to date is presented and discussed, together with a critical analysis of the most significant IL-based strategies in order to improve the performance of therapeutics and drug delivery systems.publishe

Extraction of high value triterpenic acids from eucalyptus globulus biomass using hydrophobic deep eutectic solvents

Triterpenic acids (TTAs), known for their promising biological properties, can be found in different biomass sources and related by-products, such as Eucalyptus globulus bark, and have been extracted using organic volatile solvents such as dichloromethane. Recently, deep eutectic solvents (DES) have been identified as promising alternatives for the extraction of value-added compounds from biomass. In the present work, several hydrophobic DES were tested for the extraction of TTAs from E. globulus bark. Initial solubility studies revealed that DES based on menthol and thymol as the most promising solvents for these compounds given the highest solubilities obtained for ursolic acid (UA) at temperatures ranging from room temperature up to 90 °C. Accordingly, an eutectic mixture of menthol:thymol (1:2) was confirmed as the best candidate for the TTAs extraction from E. globulus outer bark, leading to extraction yields (weight of TTA per weight of biomass) at room temperature of 1.8 wt% for ursolic acid, 0.84 wt% for oleanolic acid and 0.30 wt% for betulinic acid. These values are significantly higher than those obtained with conventional organic solvents under similar conditions. The results obtained using these DES are promising for the recovery of TTAs for nutraceutical and pharmacological applications, while reinforcing the potential of DES as promising solvents to be applied in biorefinery processes.publishe

Enhanced conversion of xylan into furfural using acidic deep eutectic solvents with dual solvent and catalyst behavior

An efficient process for the production of furfural from xylan by using acidic deep eutectic solvents (DESs), which act both as solvents and catalysts, is developed. DESs composed of cholinium chloride ([Ch]Cl) and malic acid or glycolic acid at different molar ratios, and the effects of water and γ-valerolactone (GVL) contents, solid/liquid (S/L) ratio, and microwave heating are investigated. The best furfural yields are obtained with the DES [Ch]Cl:malic acid (1:3 molar ratio)+5 wt % water, under microwave heating for 2.5 min at 150 °C, a S/L ratio of 0.050, and GVL at a weight ratio of 2:1. Under these conditions, a remarkable furfural yield (75 %) is obtained. Direct distillation of furfural from the DES/GVL solvent and distillation from 2-methyltetrahydrofuran (2-MeTHF) after a back-extraction step enable 89 % furfural recovery from 2-MeTHF. This strategy allows recycling of the DES/GVL for at least three times with only small losses in furfural yield (>69 %). This is the fastest and highest-yielding process reported for furfural production using bio-based DESs as solvents and catalysts, paving the way for scale-up of the process.publishe

A compendium of current developments on polysaccharide and protein-based microneedles

Microneedles (MNs), i.e. minimally invasive three-dimensional microstructures that penetrate the stratum corneum inducing relatively little or no pain, have been studied as appealing therapeutic vehicles for transdermal drug delivery. Over the last years, the fabrication of MNs using biopolymers, such as polysaccharides and proteins, has sparked the imagination of scientists due to their recognized biocompatibility, biodegradability, ease of fabrication and sustainable character. Owing to their wide range of functional groups, polysaccharides and proteins enable the design and preparation of materials with tunable properties and functionalities. Therefore, these biopolymer-based MNs take a revolutionary step offering great potential not only in drug administration, but also in sensing and response to physiological stimuli. In this review, a critical and comprehensive overview of the polysaccharides and proteins employed in the design and engineering of MNs will be given. The strategies adopted for their preparation, their advantages and disadvantages will be also detailed. In addition, the potential and challenges of using these matrices to deliver drugs, vaccines and other molecules will be discussed. Finally, this appraisal ends with a perspective on the possibilities and challenges in research and development of polysaccharide and protein MNs, envisioning the future advances and clinical translation of these platforms as the next generation of drug delivery systems.publishe

Nanocellulose-based antifungal nanocomposites against the polymorphic fungus Candida albicans

The design of functional materials capable of fighting fungal infections is of paramount importance given the intricate problem of multidrug-resistant pathogenic fungi. Herein, nanocomposites consisting of cross-linked poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride) (PMETAC) and bacterial nanocellulose (BNC) were prepared, characterized and tested towards the polymorphic fungus Candida albicans. The BNC three-dimensional network enabled the in-situ polymerization of the non-toxic and bioactive quaternary-ammonium monomer, which originated transparent nanocomposites containing 10 and 40 wt.% of cross-linked PMETAC. Furthermore, the nanocomposites exhibit UV-A and UV-B blocking properties, high water-uptake capacity, thermal stability up to 200 °C, good viscoelastic (storage modulus > 1.7 GPa) and mechanical (Young's modulus ≥2.4 GPa) properties and are non-cytotoxic to human keratinocytes (HaCaT cells). The fungal inactivation reached a 4.4 ± 0.14-log CFU reduction for the nanocomposite containing only 10 wt.% of cross-linked PMETAC. Hence, these bioactive and non-cytotoxic materials can constitute potentially effective systems for the treatment of C. albicans infections.publishe

Use of ionic liquids and deep eutectic solvents in polysaccharides dissolution and extraction processes towards sustainable biomass valorization

A shift to a bioeconomy development model has been evolving, conducting the scientific community to investigate new ways of producing chemicals, materials and fuels from renewable resources, i.e., biomass. Specifically, technologies that provide high performance and maximal use of biomass feedstocks into commodities with reduced environmental impact have been highly pursued. A key example comprises the extraction and/or dissolution of polysaccharides, one of the most abundant fractions of biomass, which still need to be improved regarding these processes' efficiency and selectivity parameters. In this context, the use of alternative solvents and the application of less energy-intensive processes in the extraction of polysaccharides might play an important role to reach higher efficiency and sustainability in biomass valorization. This review debates the latest achievements in sustainable processes for the extraction of polysaccharides from a myriad of biomass resources, including lignocellulosic materials and food residues. Particularly, the ability of ionic liquids (ILs) and deep eutectic solvents (DESs) to dissolve and extract the most abundant polysaccharides from natural sources, namely cellulose, chitin, starch, hemicelluloses and pectins, is scrutinized and the efficiencies between solvents are compared. The interaction mechanisms between solvent and polysaccharide are described, paving the way for the design of selective extraction processes. A detailed discussion of the work developed for each polysaccharide as well as the innovation degree and the development stage of dissolution and extraction technologies is presented. Their advantages and disadvantages are also identified, and possible synergies by integrating microwave- and ultrasound-assisted extraction (MAE and UAE) or a combination of both (UMAE) are briefly described. Overall, this review provides key information towards the design of more efficient, selective and sustainable extraction and dissolution processes of polysaccharides from biomass.publishe

Gelatin-Lysozyme Nanofibrils Electrospun Patches with Improved Mechanical, Antioxidant and Bioresorbability Properties for Myocardial Regeneration Applications

Biopolymeric patches show enormous potential for the regeneration of infarcted myocardium tissues. However, most of them usually lack appropriate mechanical performance, stability in water, and important functionalities; for instance, antioxidant activity. Protein nanofibrils, such as lysozyme nanofibrils (LNFs), are biocompatible nanostructures with excellent mechanical performance, water insolubility, and antioxidant activity exploited to fabricate materials for different biomedical applications. In this study, LNFs are used to produce gelatin electrospun nanocomposite cardiac patches with improved properties. The addition of the LNFs to the gelatin electrospun patches enhance their mechanical properties, increasing the patches Young's modulus from 3 to 6 MPa, in their wet state, which agrees with the requirements of myocardial contractility. Additionally, it is observed an increment of the antioxidant activity to 80%, by adding only 5% (w/w) of LNFs, and the bioresorbability rate is shortened to 30-35 d, compared to 45 d for the gelatin-only patches, while maintaining their morphology, and biocompatibility toward cardiomyoblasts and fibroblasts. Furthermore, 15% of a model drug is burst released from the patches and preserved for 21 d. Overall, these results demonstrate that LNFs have a great potential as functional reinforcements to fabricate biopolymeric electrospun patches for myocardial infarcted tissue regeneration.Peer reviewe

Boosting antibiotics performance by new formulations with deep eutectic solvents

The critical scenario of antimicrobial resistance to antibiotics highlights the need for improved therapeutics and/or formulations. Herein, we demonstrate that deep eutectic solvents (DES) formulations are very promising to remarkably improve the solubility, stability and therapeutic efficacy of antibiotics, such as ciprofloxacin. DES aqueous solutions enhance the solubility of ciprofloxacin up to 430-fold while extending the antibiotic stability. The developed formulations can improve, by 2 to 4-fold, the susceptibility of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria to the antibiotic. They also improve the therapeutic efficacy at concentrations where bacteria present resistance, without promoting tolerance development to ciprofloxacin. Furthermore, the incorporation of DES decreases the toxicity of ciprofloxacin towards immortalized human epidermal keratinocytes (HaCat cells). The results herein reveal the pioneering use of DES in fluoroquinolone-based formulations and their impact on the antibiotic's characteristics and on its therapeutic action.publishe

Surface hydrophobization of bacterial and vegetable cellulose fibers using ionic liquids as solvent media and catalysts

The surface hydrophobization through heterogeneous chemical modification of bacterial (and vegetable) cellulose fibers with several anhydrides (acetic, butyric, hexanoic and alkenyl succinic anhydrides) and hexanoyl chloride suspended in an ionic liquid, tetradecyltrihexylphosphonium bis(trifluoromethylsulfonyl) imide, [TDTHP][NTf(2)], was studied. Furthermore, in the reaction with hexanoyl chloride, another ionic liquid, N-hexyl-4-(dimethylamino)pyridinium bis(trifluoromethylsulfonyl) imide, [C(6)N(CH(3))(2)py][NTf(2)], was used instead of common organic bases as catalyst and to trap the released HCl. The analysis of the ensuing modified fibers by FTIR, XRD and SEM clearly showed that the esterification reactions occurred essentially at the fibers' outmost layers, not affecting their ultrastructure. The degree of substitution (DS) of the ensuing esterified fibers ranged from less than 0.002 to 0.41; and in all instances, the fibers' surface acquired a high hydrophobicity. This novel approach constitutes an important strategy in the preparation of modified fibers under greener conditions relaying in the use of non-volatile solvents.FCT - SFRH/BD/72830/2010SFRH/BPD/41781/2007PTDC/QUI/68472/2006PTDC/QUI/72903/200