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Comparative Biochemistry and... 2021Reductionist strategies aim to understand the mechanisms of complex systems by studying individual parts and their interactions. In this review, we discuss how... (Review)
Review
Reductionist strategies aim to understand the mechanisms of complex systems by studying individual parts and their interactions. In this review, we discuss how reductionist approaches have shed light on the structure, function, and production of a complex biomaterial - hagfish defensive slime. Hagfish slime is an extremely dilute hydrogel-like material composed of seawater, mucus, and silk-like proteins that can deploy rapidly. Despite being composed almost entirely of water, hagfish slime has remarkable physical properties, including high strength and toughness. While hagfish slime has a promising future in biomimetics, including the development of eco-friendly high-performance fibers, recreating hagfish slime in the lab has been a difficult challenge. Over the past two decades, reductionist experiments have provided a wealth of information about the individual components of hagfish slime. However, a reductionist approach provides a limited understanding because hagfish defensive slime, like most biological phenomena, is more than just the sum of its parts. We end by providing some thoughts about how the knowledge generated in the last few decades might be synthesized into a working model that can explain hagfish slime structure and function.
Topics: Animals; Biomimetic Materials; Hagfishes; Mucus; Seawater
PubMed: 33971350
DOI: 10.1016/j.cbpb.2021.110610 -
Advanced Drug Delivery Reviews Jan 2018Mucosal administration of drugs and drug delivery systems has gained increasing interest. However, nanoparticles intended to protect and deliver drugs to epithelial... (Review)
Review
Mucosal administration of drugs and drug delivery systems has gained increasing interest. However, nanoparticles intended to protect and deliver drugs to epithelial surfaces require transport through the surface-lining mucus. Translation from bench to bedside is particularly challenging for mucosal administration since a variety of parameters will influence the specific barrier properties of the mucus including the luminal fluids, the microbiota, the mucus composition and clearance rate, and the condition of the underlying epithelia. Besides, after administration, nanoparticles interact with the mucosal components, forming a biomolecular corona that modulates their behavior and fate after mucosal administration. These interactions are greatly influenced by the nanoparticle properties, and therefore different designs and surface-engineering strategies have been proposed. Overall, it is essential to evaluate these biomolecule-nanoparticle interactions by complementary techniques using complex and relevant mucus barrier matrices.
Topics: Animals; Drug Delivery Systems; Humans; Mucus; Nanoparticles; Surface Properties
PubMed: 29117511
DOI: 10.1016/j.addr.2017.11.002 -
Respiratory Care Dec 2022
Topics: Humans; Mucus
PubMed: 36442989
DOI: 10.4187/respcare.10675 -
Gut Microbes 2022Over the past two decades, our appreciation of the gut mucus has moved from a static lubricant to a dynamic and essential component of the gut ecosystem that not only... (Review)
Review
Over the past two decades, our appreciation of the gut mucus has moved from a static lubricant to a dynamic and essential component of the gut ecosystem that not only mediates the interface between host tissues and vast microbiota, but regulates how this ecosystem functions to promote mutualistic symbioses and protect from microbe-driven diseases. By delving into the complex chemistry and biology of the mucus, combined with innovative in vivo and ex vivo approaches, recent studies have revealed novel insights into the formation and function of the mucus system, the O-glycans that make up this system, and how they mediate two major host-defense strategies - resistance and tolerance - to reduce damage caused by indigenous microbes and opportunistic pathogens. This current review summarizes these findings by highlighting the emerging roles of mucus and mucin-type O-glycans in influencing host and microbial physiology with an emphasis on host defense strategies against bacteria in the gastrointestinal tract.
Topics: Gastrointestinal Microbiome; Glycosylation; Intestinal Mucosa; Microbiota; Mucins; Mucus; Symbiosis
PubMed: 35380912
DOI: 10.1080/19490976.2022.2052699 -
European Journal of Pharmaceutics and... Oct 2015The present review provides an overview of nanotechnology-based strategies to overcome various mucus gel barriers including the intestinal, nasal, ocular, vaginal,... (Review)
Review
The present review provides an overview of nanotechnology-based strategies to overcome various mucus gel barriers including the intestinal, nasal, ocular, vaginal, buccal and pulmonary mucus layer without destroying them. It focuses on the one hand on strategies to improve the mucus permeation behavior of particles and on the other hand on systems avoiding the back-diffusion of particles out of the mucus gel layer. Nanocarriers with improved mucus permeation behavior either exhibit a high density of positive and negative charges, bearing mucolytic enzymes such as papain and bromelain on their surface or display a slippery surface due to PEG-ylation. Furthermore, self-nanoemulsifying-drug-delivery-systems (SNEDDS) turned out to exhibit comparatively high mucus permeating properties. Strategies in order to avoid back-diffusion are based on thiolated polymers reacting to a higher extent with cysteine subunits of the mucus at pH 7 in deeper mucus regions than at pH 5 being prevalent in luminal mucus regions of the intestinal and vaginal mucosa. Furthermore, particles changing their zeta potential from negative to positive once they have reached the epithelium seem to be promising carriers. The summarized knowledge should provide a good starting point for further developments in this field.
Topics: Absorption, Physiological; Animals; Diffusion; Drug Carriers; Drug Delivery Systems; Emulsions; Expectorants; Humans; Hydrogen-Ion Concentration; Mucous Membrane; Mucus; Nanostructures; Peptide Hydrolases; Permeability; Pharmacokinetics; Proteolysis; Surface Properties
PubMed: 25712487
DOI: 10.1016/j.ejpb.2015.01.022 -
Advanced Drug Delivery Reviews Jan 2018The increasing interest in developing tools to predict drug absorption through mucosal surfaces is fostering the establishment of epithelial cell-based models.... (Review)
Review
The increasing interest in developing tools to predict drug absorption through mucosal surfaces is fostering the establishment of epithelial cell-based models. Cell-based in vitro techniques for drug permeability assessment are less laborious, cheaper and address the concerns of using laboratory animals. Simultaneously, in vitro barrier models that thoroughly simulate human epithelia or mucosae may provide useful data to speed up the entrance of new drugs and new drug products into the clinics. Nevertheless, standard cell-based in vitro models that intend to reproduce epithelial surfaces often discard the role of mucus in influencing drug permeation/absorption. Biomimetic models of mucosae in which mucus production has been considered may not be able to fully reproduce the amount and architecture of mucus, resulting in biased characterization of permeability/absorption. In these cases, artificial mucus may be used to supplement cell-based models but still proper identification and quantification are required. In this review, considerations regarding the relevance of mucus in the development of cell-based epithelial and mucosal models mimicking the gastro-intestinal tract, the cervico-vaginal tract and the respiratory tract, and the impact of mucus on the permeability mechanisms are addressed. From simple epithelial monolayers to more complex 3D structures, the impact of the presence of mucus for the extrapolation to the in vivo scenario is critically analyzed. Finally, an overview is provided on several techniques and methods to characterize the mucus layer over cell-based barriers, in order to intimately reproduce human mucosal layer and thereby, improve in vitro/in vivo correlation.
Topics: Animals; Drug Delivery Systems; Gastric Mucosa; Humans; Intestine, Small; Models, Biological; Mucus
PubMed: 28751201
DOI: 10.1016/j.addr.2017.07.019 -
American Journal of Respiratory and... Mar 2020Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these... (Comparative Study)
Comparative Study
Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these abnormalities has not been characterized. This study was designed to: ) measure mucus concentration and biophysical properties of bronchiectasis mucus; ) identify the secreted mucins contained in bronchiectasis mucus; ) relate mucus properties to airway epithelial mucin RNA/protein expression; and ) explore relationships between mucus hyperconcentration and disease severity. Sputum samples were collected from subjects with bronchiectasis, with and without chronic erythromycin administration, and healthy control subjects. Sputum percent solid concentrations, total and individual mucin concentrations, osmotic pressures, rheological properties, and inflammatory mediators were measured. Intracellular mucins were measured in endobronchial biopsies by immunohistochemistry and gene expression. MUC5B (mucin 5B) polymorphisms were identified by quantitative PCR. In a replication bronchiectasis cohort, spontaneously expectorated and hypertonic saline-induced sputa were collected, and mucus/mucin concentrations were measured. Bronchiectasis sputum exhibited increased percent solids, total and individual (MUC5B and MUC5AC) mucin concentrations, osmotic pressure, and elastic and viscous moduli compared with healthy sputum. Within subjects with bronchiectasis, sputum percent solids correlated inversely with FEV and positively with bronchiectasis extent, as measured by high-resolution computed tomography, and inflammatory mediators. No difference was detected in rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced non-cystic fibrosis bronchiectasis mucus concentration by 5%. Hyperconcentrated airway mucus is characteristic of subjects with bronchiectasis, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy.
Topics: Aged; Bronchiectasis; Cohort Studies; Erythromycin; Female; Humans; Male; Middle Aged; Mucus; Queensland; Respiratory System; Sputum
PubMed: 31765597
DOI: 10.1164/rccm.201906-1219OC -
Frontiers in Cellular and Infection... 2017The human gut is colonized by a variety of large amounts of microbes that are collectively called intestinal microbiota. Most of these microbial residents will grow... (Review)
Review
The human gut is colonized by a variety of large amounts of microbes that are collectively called intestinal microbiota. Most of these microbial residents will grow within the mucus layer that overlies the gut epithelium and will act as the first line of defense against both commensal and invading microbes. This mucus is essentially formed by mucins, a family of highly glycosylated protein that are secreted by specialize cells in the gut. In this Review, we examine how commensal members of the microbiota and pathogenic bacteria use mucus to their advantage to promote their growth, develop biofilms and colonize the intestine. We also discuss how mucus-derived components act as nutrient and chemical cues for adaptation and pathogenesis of bacteria and how bacteria can influence the composition of the mucus layer.
Topics: Animals; Bacteria; Bacterial Adhesion; Biofilms; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mice; Mucins; Mucus; Virulence
PubMed: 28929087
DOI: 10.3389/fcimb.2017.00387 -
European Journal of Pharmaceutics and... Apr 2020Lungs are critical organs that are continuously exposed to exogeneous matter. The presence of the mucus layer helps to protect them via its adhesive structure and...
Lungs are critical organs that are continuously exposed to exogeneous matter. The presence of the mucus layer helps to protect them via its adhesive structure and filtering mechanisms. Mucus also acts as a strong barrier against the drugs and nanocarriers in drug delivery. In this study, solid lipid nanoparticles (SLNs), at different sizes and surface properties, were prepared and their spreading/penetration ability was tested for their use in pulmonary drug delivery. The biophysical interactions of SLNs have been studied via light scattering (LS) and zeta potential analyses by incubating the SLNs in mucin solution and forming a model mucus layer using a Langmuir-Blodgett (LB) trough. In addition, the penetration performance of the particles was evaluated using Franz diffusion cell and rotating diffusion tubes. It was determined that 36% of SLNs can penetrate through a 1.2 ± 0.2-mm-thick mucus layer. Finally, the spreading behavior of the particles on a mucus-mimicking subphase was characterized and enhanced using a catanionic surfactant mixture. Overall, the current study was the first to investigates both the spreading and penetration performance of SLNs. The developed systems offer a drug delivery system that is able to achieve high penetration rates through a thick mucus layer.
Topics: Animals; Drug Carriers; Drug Delivery Systems; Lipids; Lung; Mucins; Mucus; Nanoparticles; Particle Size; Surface Properties; Surface-Active Agents; Swine
PubMed: 32014491
DOI: 10.1016/j.ejpb.2020.01.017 -
International Journal of Molecular... Sep 2021The gastrointestinal tract is optimized to efficiently absorb nutrients and provide a competent barrier against a variety of lumen environmental compounds. Different... (Review)
Review
The gastrointestinal tract is optimized to efficiently absorb nutrients and provide a competent barrier against a variety of lumen environmental compounds. Different regulatory mechanisms jointly collaborate to maintain intestinal homeostasis, but alterations in these mechanisms lead to a dysfunctional gastrointestinal barrier and are associated to several inflammatory conditions usually found in chronic pathologies such as inflammatory bowel disease (IBD). The gastrointestinal mucus, mostly composed of mucin glycoproteins, covers the epithelium and plays an essential role in digestive and barrier functions. However, its regulation is very dynamic and is still poorly understood. This review presents some aspects concerning the role of mucus in gut health and its alterations in IBD. In addition, the impact of gut microbiota and dietary compounds as environmental factors modulating the mucus layer is addressed. To date, studies have evidenced the impact of the three-way interplay between the microbiome, diet and the mucus layer on the gut barrier, host immune system and IBD. This review emphasizes the need to address current limitations on this topic, especially regarding the design of robust human trials and highlights the potential interest of improving our understanding of the regulation of the intestinal mucus barrier in IBD.
Topics: Animals; Diet; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Mucus; Nutrients
PubMed: 34638564
DOI: 10.3390/ijms221910224