Biopolymeric injectable hydrogels are promising biomaterials for myocardial regeneration applications. Besides being biocompatible, they adjust themselves, perfectly fitting the surrounding tissue. ...However, due to their nature, biopolymeric hydrogels usually lack desirable functionalities, such as antioxidant activity and electrical conductivity, and in some cases, mechanical performance. Protein nanofibrils (NFs), such as lysozyme nanofibrils (LNFs), are proteic nanostructures with excellent mechanical performance and antioxidant activity, which can work as nanotemplates to produce metallic nanoparticles. Here, gold nanoparticles (AuNPs) were synthesized in situ in the presence of LNFs, and the obtained hybrid AuNPs@LNFs were incorporated into gelatin-hyaluronic acid (HA) hydrogels for myocardial regeneration applications. The resulting nanocomposite hydrogels showed improved rheological properties, mechanical resilience, antioxidant activity, and electrical conductivity, especially for the hydrogels containing AuNPs@LNFs. The swelling and bioresorbability ratios of these hydrogels are favorably adjusted at lower pH levels, which correspond to the ones in inflamed tissues. These improvements were observed while maintaining important properties, namely, injectability, biocompatibility, and the ability to release a model drug. Additionally, the presence of AuNPs allowed the hydrogels to be monitorable through computer tomography. This work demonstrates that LNFs and AuNPs@LNFs are excellent functional nanostructures to formulate injectable biopolymeric nanocomposite hydrogels for myocardial regeneration applications.
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The purification of value-added compounds by three-phase partitioning (TPP) is a promising alternative to conventional processes since the target compound can be easily recovered from the ...liquid–liquid interphase. Although this technique has been successfully applied to the recovery of proteins, the minimization of the use of salts and solvents must be pursued to improve the overall process sustainability. Accordingly, we have here investigated the use of biobased glycine-betaine ionic liquids (IL) directly with honey, a carbohydrate-rich matrix, as phase-forming components of TPP systems. These ILTPP systems were applied in the purification of major royal jelly proteins (MRJPs) from honey. The results obtained show that MRJPs mostly precipitate in the ILTPP interphase, with a recovery yield ranging between 82.8% and 97.3%. In particular, MRJP1 can be obtained with a purity level up to 90.1%. Furthermore, these systems allow the simultaneous separation of antioxidants and carbohydrates to different liquid phases. The proposed approach allows the separation of proteins, antioxidants, and carbohydrates from honey in a single step, while using only ILs and a real carbohydrate-rich matrix, thus being sustainable TPP processes.
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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.
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The transdermal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is a valuable and safer alternative to their oral intake. However, most of these drugs display low water solubility, ...which makes their incorporation into hydrophilic biopolymeric drug-delivery systems difficult. To overcome this drawback, aqueous solutions of bio-based deep eutectic solvents (DES) were investigated to enhance the solubility of ibuprofen, a widely used NSAID, leading to an increase in its solubility of up to 7917-fold when compared to its water solubility. These DES solutions were shown to be non-toxic to macrophages with cell viabilities of 97.4% (at ibuprofen concentrations of 0.25 mM), while preserving the anti-inflammatory action of the drug. Their incorporation into alginate-based hydrogels resulted in materials with a regular structure and higher flexibility. These hydrogels present a sustained release of the drug, which is able, when containing the DES aqueous solution comprising ibuprofen, to deliver 93.5% of the drug after 8 h in PBS. Furthermore, these hydrogels were able to improve the drug permeation across human skin by 8.5-fold in comparison with the hydrogel counterpart containing only ibuprofen. This work highlights the possibility to remarkably improve the transdermal administration of NSAIDs by combining new drug formulations based on DES and biopolymeric drug delivery systems.
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Antimicrobial photodynamic therapy (aPDT) is a potent tool to surpass the global rise of antimicrobial resistance; still, the effective topical administration of photosensitizers remains a challenge. ...Biopolymer-based adhesive films can safely extend the residence time of photosensitizers. However, their wide application is narrowed by their limited water absorption capacity and gel strength. In this study, pullulan-based films with a switchable character (from a solid film to an adhesive hydrogel) were developed. This was accomplished by the incorporation of a betaine-based deep eutectic solvent (DES) containing curcumin (4.4 μg.cm−2) into the pullulan films, which tuned the films’ skin moisture absorption ability, and therefore they switch into an adhesive hydrogel capable of delivering the photosensitizer. The obtained transparent films presented higher extensibility (elongation at break up to 338.2%) than the pullulan counterparts (6.08%), when stored at 54% of relative humidity, and the corresponding hydrogels a 4-fold higher adhesiveness than commercial hydrogels. These non-cytotoxic adhesives allowed the inactivation (∼5 log reduction), down to the detection limit of the method, of multiresistant strains of Staphylococcus aureus in ex vivo skin samples. Overall, these materials are promising for aPDT in the treatment of resistant skin infections, while being easily removed from the skin.
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Introduction: Deep eutectic solvents comprising or acting as solvents of active pharmaceutical ingredients (API-DES) emerged as promising alternatives to improve therapeutic efficiency, with the ...additional possibility to integrate them in (bio)polymer-based systems to enhance their delivery.
Areas covered: A critical review of the API-DES field evolution is herein presented, namely on the capacity of DES to integrate APIs in their composition and on the use of DES as solvents for APIs. These strategies avoid a current major concern related to drugs and APIs, i.e. polymorphism, and increase the solubility and bioavailability of the target API which leads to increased bioavailability. Owing to their composition versatility, polymerizable API-DES can also be prepared. Finally, the incorporation of API-DES in (bio)polymer-based systems to improve drug delivery is presented and discussed.
Expert opinion: The relatively easy preparation of API-DES and their capacity to tune the API's release profile when incorporated in (bio)polymer-based systems represent an effective alternative to improve the APIs therapeutic action and to develop controlled drug delivery systems. Given the potential and progress demonstrated so far, the authors foresee further research on novel API-DES and on their delivery routes, envisaging the development of alternative therapies and final approval as therapeutics.
Aiming at establishing more effective and sustainable separation processes, herein we propose the use of carbohydrates combined with tetralkylphosphonium- and tetralkylammonium-based ionic liquids ...(ILs) to form aqueous biphasic systems (ABS). The formation of ABS composed of non-aromatic and non-fluorinated ILs with carbohydrates is here shown for the first time. These novel systems are competive extraction platforms when compared against more conventional ABS formed by ILs and salts or fluorinated ILs and carbohydrates. Finally, it is shown that these systems can be efficiently recovered and reused.
•Novel ABS composed of phosphonium- and ammonium-based ionic liquids were investigated.•The performance of the studied ABS for the extraction of BSA was evaluated.•Extraction efficiencies of 100% of ...BSA were achieved in a single-step.•The recovery of the protein and the recyclability of the ionic liquids was demonstrated.•The stability of BSA after the extraction step was confirmed.
Novel aqueous biphasic systems (ABS) composed of phosphonium- or ammonium-based ionic liquids (ILs), combined with a buffered aqueous solution of potassium citrate/citric acid (pH=7.0), were investigated for the extraction of proteins. For that purpose, the phase diagrams, tie-lines and tie-line lengths were determined at 25°C, and the performance of these ABS for the extraction of bovine serum albumin (BSA) was then evaluated. The obtained results reveal that, with the exception of the more hydrophobic ILs, most of the systems investigated allow the complete extraction of BSA for the IL-rich phase in a single-step. These remarkable extraction efficiencies are far superior to those afforded by more conventional extraction systems previously reported. The composition of the biphasic systems, i.e., the amount of phase-forming components, was also investigated aiming at reducing the overall costs of the process without losing efficiency on the protein extraction. It is shown that the extraction efficiencies of BSA are maintained at 100% up to high protein concentrations (at least up to 10gL−1). The recovery of the BSA from the IL-rich phase by dialysis is also shown in addition to the demonstration of the IL recyclability and reusability, at least for 3 times. In the sequential three-step extractions (BSA recovery/IL reusability), the extraction efficiencies of BSA for the IL-rich phase were maintained at 100%. For the improved ABS, the preservation of the protein native conformation was confirmed by Size Exclusion High-Performance Liquid Chromatography (used also as the quantification method) and by Fourier Transform Infra-Red spectroscopy. According to the results herein reported, ABS composed of phosphonium- or ammonium-based ILs and a biodegradable organic salt represent an alternative and remarkable platform for the extraction of BSA and may be extended to other proteins of interest.
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Deep Eutectic Solvents and Pharmaceuticals Pedro, Sónia N.; Freire, Carmen S. R.; Silvestre, Armando J. D. ...
Encyclopedia (Basel, Switzerland),
09/2021, Volume:
1, Issue:
3
Journal Article
Peer reviewed
Open access
Deep eutectic solvents (DES) are eutectic mixtures that present a deviation from the ideal thermodynamic solid–liquid phase behavior, where a significant depression in the melting temperature occurs. ...If properly designed and chosen, DES may be liquid at room and the human body’s temperatures and display a biocompatible character, thus representing relevant options in the pharmaceutical field. Accordingly, DES have been studied as alternative solvents or in formulations of pharmaceuticals to improve their solubility and stability. Depending on the DES components, these mixtures might exhibit interesting biological activities compatible with several applications. The use of DES as functional agents or as novel liquid forms of active pharmaceutical ingredients (API-DES) with the goal of improving bioavailability, permeability and therapeutic efficacy of a given API stands as alternative strategies in the pharmaceutical field for drug delivery purposes.
Ionic Liquids in Drug Delivery Pedro, Sónia N.; Freire, Carmen S. R.; Silvestre, Armando J. D. ...
Encyclopedia (Basel, Switzerland),
04/2021, Volume:
1, Issue:
2
Journal Article
Peer reviewed
Open access
Ionic liquids (ILs) are molten salts composed of a large organic cation and an organic/inorganic anion. Due to their ionic character, most ILs present advantageous properties over conventional ...solvents, such as negligible volatility at atmospheric conditions and high thermal and chemical stabilities. The wide variety of IL anion–cation combinations allows these solvents to be designed to display a strong solvation ability for a myriad of active pharmaceutical ingredients (APIs) and (bio)polymers. Given these properties, ILs have been used as solvents and as formulation components in different areas of drug delivery, as well as novel liquid forms of APIs (API-ILs) applied in different stages of development of novel drug delivery systems. Furthermore, their combination with polymers and biopolymers has enabled the design of drug delivery systems for new therapeutic routes of administration.
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