Versatile applications of deep eutectic solvents in drug discovery and drug delivery systems: Perspectives and opportunities
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PROVIDER: S-EPMC9950417 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:As functional liquid media, natural deep eutectic solvent (NADES) species can dissolve natural or synthetic chemicals of low water solubility. Moreover, the special properties of NADES, such as biodegradability and biocompatibility, suggest that they are alternative candidates for concepts and applications involving some organic solvents and ionic liquids. Owing to the growing comprehension of the eutectic mechanisms and the advancing interest in the natural eutectic phenomenon, many NADES applications have been developed in the past several years. However, unlike organic solvents, the basic structural unit of NADES media primarily depends on the intermolecular interactions among their components. This makes NADES matrices readily influenced by various factors, such as water content, temperature, and component ratio and, thus, extends the metabolomic challenge of natural products (NPs). To enhance the understanding of the importance of NADES in biological systems, this review focuses on NADES properties and applications in NP research. The present thorough chronological and statistical analysis of existing report adds to the recognition of the distinctiveness of (NA)DES, involves a discussion of NADES-related observations in NP research, and reportes applications of these eutectic mixtures. The work identifies potential areas for future studies of (NA)DES by evaluating relevant applications, including their use as extraction and chromatographic media as well as their biomedical relevance. The chemical diversity of natural metabolites that generate or participate in NADES formation highlights the growing insight that biosynthetically primordial metabolites (PRIMs) are as essential to the biological function and bioactivity of unrefined natural products as the biosynthetically more highly evolutionary metabolites (HEVOs) that can be isolated from crude mixtures.
| S-EPMC5913660 | biostudies-literature
Project description:Administering medicines to 0- to 5-year-old children in a resource-limited environment requires dosage forms that circumvent swallowing solids, avoid on-field reconstitution, and are thermostable, cheap, versatile, and taste masking. We present a strategy that stands to solve this multifaceted problem. As many drugs lack adequate water solubility, our formulations used oils, whose textures could be modified with gelling agents to form "oleogels." In a clinical study, we showed that the oleogels can be formulated to be as fluid as thickened beverages and as stiff as yogurt puddings. In swine, oleogels could deliver four drugs ranging three orders of magnitude in their water solubilities and two orders of magnitude in their partition coefficients. Oleogels could be stabilized at 40°C for prolonged durations and used without redispersion. Last, we developed a macrofluidic system enabling fixed and metered dosing. We anticipate that this platform could be adopted for pediatric dosing, palliative care, and gastrointestinal disease applications.
| S-EPMC9140966 | biostudies-literature
Project description:Proteins are among the most common therapeutics for the treatment of diabetes, autoimmune diseases, cancer, and metabolic diseases, among others. Despite their common use, current protein therapies, most of which are injectables, have several limitations. Large proteins such as monoclonal antibodies (mAbs) suffer from poor absorption after subcutaneous injections, thus forcing their administration by intravenous injections. Even small proteins such as insulin suffer from slow pharmacokinetics which poses limitations in effective management of diabetes. Here, a deep eutectic-based delivery strategy is used to offer a generalized approach for improving protein absorption after subcutaneous injections. The lead formulation enhances absorption of mAbs after subcutaneous injections by ≈200%. The same composition also improves systemic absorption of subcutaneously injected insulin faster than Humalog, the current gold-standard of rapid acting insulin. Mechanistic studies reveal that the beneficial effect of deep eutectics on subcutaneous absorption is mediated by their ability to reduce the interactions of proteins with the subcutaneous matrix, especially collagen. Studies also confirm that these deep eutectics are safe for subcutaneous injections. Deep eutectic-based formulations described here open new possibilities for subcutaneous injections of therapeutic proteins.
| S-EPMC9982585 | biostudies-literature
Project description:Senescent cells accumulate in many ageing-associated diseases such as pulmonary fibrosis, and targeting these cells has recently emerged as a promising therapeutic approach. Here, we take advantage of the high β-galactosidase activity of senescent cells to design a targeted drug delivery system based on the encapsulation of drugs with galacto-oligosaccharides (GalNP beads). In this experiment we show that gal-encapsulated rhodamine target senescent cells in the context of pulmonary fibrosis in mice.
2018-07-05 | GSE97685 | GEO
Project description:Owing to a growing awareness toward environmental impact, the use of safer and eco-friendly solvents like deep eutectic solvents (DESs), has recently undergone important growth in the pharmaceutical field, with regard to their application as non-aqueous liquid administration vehicles, since they do not carry the same risks of toxicity and handling as traditional organic solvents. Major attention has been given to the development of advantageous transdermal drug delivery systems, because of their ease of use and better acceptability. Here, we report the use of two different DESs, based on choline chloride, used as hydrogen bond acceptor (HBA), and ascorbic acid or propylene glycol, used as hydrogen bond donors (HBDs), able to enhance the solubility and the topical delivery of dapsone, representing a class IV drug. The interactions between the DESs' components and the drug were studied by performing DSC, FT-IR, and NMR analysis of the eutectic systems and the pure drug, confirming the establishment of H-bonds between the drug and the DESs' components. Diffusion and permeability studies, carried out in a Franz cell, showed an increase in permeability, highlighting the great potential of DESs as dissolution and permeation enhancers in the development of novel and more effective drug delivery systems in topical administration.
| S-EPMC8875782 | biostudies-literature
Project description:Cystic fibrosis (CF) is a complex, potentially life-threatening disease that is most effectively treated through the administration of antibiotics (e.g., colistimethate sodium). Chronic infection with Pseudomonas aeruginosa is one of the most significant events in the pathogenesis of cystic fibrosis, and tobramycin is the treatment of choice for those patients with chronic P. aeruginosa infection who are deteriorating despite regular administration of colistimethate sodium. Effective treatment can be challenging due to the accumulation of thickened mucus in the pulmonary environment, and here we describe the results of our investigation into the development of alginate/chitosan particles prepared via precipitation for such environments. Tobramycin loading and release from the alginate/chitosan particles was investigated, with evidence of both uptake and release of sufficient tobramycin to inhibit P. aeruginosa in vitro. Functionalisation of the alginate/chitosan particles with secretory leukocyte protease inhibitor (SLPI) was shown to help inhibit the inflammatory response associated with lung infections (via inhibition of neutrophil elastase activity) and enhance their interaction with cystic fibrosis mucus (assayed via reduction of the depth of particle penetration into the mucus) in vitro, which have prospects to enhance their efficacy in vivo.
| S-EPMC6722511 | biostudies-literature
Project description:Poor water solubility and low bioavailability of active pharmaceutical ingredients (APIs) are major causes of friction in the pharmaceutical industry and represent a formidable hurdle for pharmaceutical drug development. Drug delivery remains the major challenge for the application of new small-molecule drugs as well as biopharmaceuticals. The three challenges for synthetic delivery systems are: (i) controlling drug distribution and clearance in the blood; (ii) solubilizing poorly water-soluble agents, and (iii) selectively targeting specific tissues. Although several polymer-based systems have addressed the first two demands and have been translated into clinical practice, no targeted synthetic drug delivery system has reached the market. This Review is designed to provide a background on the challenges and requirements for the design and translation of new polymer-based delivery systems. This report will focus on chemical approaches to drug delivery for systemic applications.
| S-EPMC10091760 | biostudies-literature
Project description:Aqueous two-phase systems (ATPSs) are liquid-liquid equilibria between two aqueous phases that usually contain over 70% water content each, which results in a nontoxic organic solvent-free environment for biological compounds and biomolecules. ATPSs have attracted significant interest in applications for formulating carriers (microparticles, nanoparticles, hydrogels, and polymersomes) which can be prepared using the spontaneous phase separation of ATPSs as a driving force, and loaded with a wide range of bioactive materials, including small molecule drugs, proteins, and cells, for delivery applications. This review provides a detailed analysis of various ATPSs, including strategies employed for particle formation, polymerization of droplets in ATPSs, phase-guided block copolymer assemblies, and stimulus-responsive carriers. Processes for loading various bioactive payloads are discussed, and applications of these systems for drug delivery are summarized and discussed.
| S-EPMC11245733 | biostudies-literature
Project description:Natural deep eutectic solvents (NADESs) are considered as green solvents, and due to their promising sustainability, they have been applied in many research fields. In this study, the main goal is to use various NADES systems to replace the traditional solvents used in conservation and restoration to remove varnish layers in a painting. The toxicity of traditional solvents, such as toluene or acetone, is well known in the chemistry field. To replace them, it is important to understand the intrinsic physicochemical properties of a solvent that may act as a substitute. Polarity and solubility are proposed as the best parameters required for this study. The Nile red probe was used to confirm the similarity between the polarity of deep eutectic systems (DESs) and traditional solvents. According to their polarities and Hansen solubility parameters, it is possible to predict the best solvents to solubilize the natural resin varnishes. Besides this, some arithmetic models can also be applied to estimate the critical or thermodynamic properties, which are useful tools to predict the behavior of these solvents. We have further proven the possibility of dissolving natural varnishes such as dammar or mastic in hydrophobic DESs, such as menthol + lauric acid, menthol + decanoic acid, or menthol + thymol.
| S-EPMC8612153 | biostudies-literature
Project description:Gastrointestinal cancers are characterized by a frequent incidence, a high number of associated deaths, and a tremendous burden on the medical system and patients worldwide. As conventional chemotherapeutic drugs face numerous limitations, researchers started to investigate better alternatives for extending drug efficacy and limiting adverse effects. A remarkably increasing interest has been addressed to chitosan and cyclodextrins, two highly versatile natural carbohydrate materials endowed with unique physicochemical properties. In this respect, numerous studies reported on fabricating various chitosan and cyclodextrin-based formulations that enabled prolonged circulation times, improved cellular internalization of carried drugs, preferential uptake by the targeted cells, reduced side effects, enhanced apoptosis rates, and increased tumor suppression rates. Therefore, this paper aims to briefly present the advantageous properties of these oligo- and polysaccharides for designing drug delivery systems, further focusing the discussion on nanocarrier systems based on chitosan/cyclodextrins for treating different gastrointestinal cancers. Specifically, there are reviewed studies describing promising solutions for colorectal, liver, gastric, pancreatic, and other types of cancers of the digestive system towards creating an updated framework of what concerns anticancer chitosan/cyclodextrin-based drug delivery systems.
| S-EPMC10819812 | biostudies-literature