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Immunological Reviews Jul 2014The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins... (Review)
Review
The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103(+) type. In addition to the gel-forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy.
Topics: Animals; Enterocytes; Gastrointestinal Tract; Goblet Cells; Humans; Immune System; Mucins; Mucous Membrane; Mucus; Peyer's Patches
PubMed: 24942678
DOI: 10.1111/imr.12182 -
Journal of the American Chemical Society Nov 2022Mucus hydrogels at biointerfaces are crucial for protecting against foreign pathogens and for the biological functions of the underlying cells. Since mucus can bind to... (Review)
Review
Mucus hydrogels at biointerfaces are crucial for protecting against foreign pathogens and for the biological functions of the underlying cells. Since mucus can bind to and host both viruses and bacteria, establishing a synthetic model system that can emulate the properties and functions of native mucus and can be synthesized at large scale would revolutionize the mucus-related research that is essential for understanding the pathways of many infectious diseases. The synthesis of such biofunctional hydrogels in the laboratory is highly challenging, owing to their complex chemical compositions and the specific chemical interactions that occur throughout the gel network. In this perspective, we discuss the basic chemical structures and diverse physicochemical interactions responsible for the unique properties and functions of mucus hydrogels. We scrutinize the different approaches for preparing mucus-inspired hydrogels, with specific examples. We also discuss recent research and what it reveals about the challenges that must be addressed and the opportunities to be considered to achieve desirable synthetic mucus hydrogels.
Topics: Hydrogels; Mucus; Bacteria
PubMed: 36074739
DOI: 10.1021/jacs.1c13547 -
Advanced Drug Delivery Reviews Nov 2021In vitro cell-based models have been used for a long time since they are normally easily obtained and have an advantageous cost-benefit. Besides, they can serve a... (Review)
Review
In vitro cell-based models have been used for a long time since they are normally easily obtained and have an advantageous cost-benefit. Besides, they can serve a variety of ends, from studying drug absorption and metabolism to disease modeling. However, some in vitro models are too simplistic, not accurately representing the living tissues. It has been shown, mainly in the last years, that fully mimicking a tissue composition and architecture can be paramount for cellular behavior and, consequently, for the outcomes of the studies using such models. Because of this, 3D in vitro cell models have been gaining much attention, since they are able to better replicate the in vivo environment. In this review we focus on 3D models that contain mucus-producing cells, as mucus can play a pivotal role in drug absorption. Being frequently overlooked, this viscous fluid can have an impact on drug delivery. Thus, the aim of this review is to understand to which extent can mucus affect mucosal drug delivery and to provide a state-of-the-art report on the existing 3D cell-based mucus models.
Topics: Cell Culture Techniques, Three Dimensional; Humans; Models, Biological; Mucus
PubMed: 34619286
DOI: 10.1016/j.addr.2021.113993 -
Annual Review of Biomedical Engineering Jun 2018Mucus selectively controls the transport of molecules, particulate matter, and microorganisms to the underlying epithelial layer. It may be desirable to weaken the mucus... (Review)
Review
Mucus selectively controls the transport of molecules, particulate matter, and microorganisms to the underlying epithelial layer. It may be desirable to weaken the mucus barrier to enable effective delivery of drug carriers. Alternatively, the mucus barrier can be strengthened to prevent epithelial interaction with pathogenic microbes or other exogenous materials. The dynamic mucus layer can undergo changes in structure (e.g., pore size) and/or composition (e.g., protein concentrations, mucin glycosylation) in response to stimuli that occur naturally or are purposely administered, thus altering its barrier function. This review outlines mechanisms by which mucus provides a selective barrier and methods to engineer the mucus layer from the perspective of strengthening or weakening its barrier properties. In addition, we discuss strategic design of drug carriers and dosing formulation properties for efficient delivery across the mucus barrier.
Topics: Animals; Bacteria; Drug Carriers; Drug Delivery Systems; Humans; Lactobacillus; Mice; Mucus; Nanoparticles; Particle Size; Permeability; Probiotics; Rats; Rheology; Staphylococcus aureus; Viscosity
PubMed: 29865871
DOI: 10.1146/annurev-bioeng-062117-121156 -
Advanced Drug Delivery Reviews Jan 2018Mucus is a complex hydrogel that acts as a natural barrier to drug delivery at different mucosal surfaces including the respiratory, gastrointestinal, and vaginal... (Review)
Review
Mucus is a complex hydrogel that acts as a natural barrier to drug delivery at different mucosal surfaces including the respiratory, gastrointestinal, and vaginal tracts. To elucidate the role mucus plays in drug delivery, different in vitro, in vivo, and ex vivo mucus models and techniques have been utilized. Drug and drug carrier diffusion can be studied using various techniques in either isolated mucus gels or mucus present on cell cultures and tissues. The species, age, and potential disease state of the animal from which mucus is derived can all impact mucus composition and structure, and therefore impact drug and drug carrier diffusion. This review provides an overview of the techniques used to characterize drug and drug carrier diffusion, and discusses the advantages and disadvantages of the different models available to highlight the information they can afford.
Topics: Animals; Diffusion; Drug Delivery Systems; Humans; Models, Biological; Mucus; Particle Size; Pharmaceutical Preparations
PubMed: 29117512
DOI: 10.1016/j.addr.2017.11.001 -
Frontiers in Immunology 2021The airway mucus barrier is a primary defensive layer at the airway surface. Mucins are the major structural components of airway mucus that protect the respiratory... (Review)
Review
The airway mucus barrier is a primary defensive layer at the airway surface. Mucins are the major structural components of airway mucus that protect the respiratory tract. Respiratory viruses invade human airways and often induce abnormal mucin overproduction and airway mucus secretion, leading to airway obstruction and disease. The mechanism underlying the virus-induced abnormal airway mucus secretion has not been fully studied so far. Understanding the mechanisms by which viruses induce airway mucus hypersecretion may open new avenues to treatment. In this article, we elaborate the clinical and experimental evidence that respiratory viruses cause abnormal airway mucus secretion, review the underlying mechanisms, and also discuss the current research advance as well as potential strategies to treat the abnormal airway mucus secretion caused by SARS-CoV-2.
Topics: Animals; Humans; Mucus; Respiratory System; Virus Diseases
PubMed: 34650550
DOI: 10.3389/fimmu.2021.701443 -
Otolaryngologic Clinics of North America Feb 2010A variety of mucoactive medications are used to treat chronic lung disease. When evaluating the role of the cough, it must be considered as an important protective... (Review)
Review
A variety of mucoactive medications are used to treat chronic lung disease. When evaluating the role of the cough, it must be considered as an important protective mechanism. Therefore, it may be more important to improve the effectiveness of cough than to suppress or eliminate a chronic cough in patients with chronic lung disease. This article discusses the composition of mucus and phlegm, the process of mucin secretion and mucus clearance, and reviews current therapy and mucolytics in use or being studied for mucus clearance disorders.
Topics: Cough; Expectorants; Humans; Lung Diseases; Mucins; Mucus; Rheology
PubMed: 20172254
DOI: 10.1016/j.otc.2009.11.002 -
Respiratory Research Nov 2019Mucus secretion and mucociliary transport are essential defense mechanisms of the airways. Deviations in mucus composition and secretion can impede mucociliary transport... (Review)
Review
Mucus secretion and mucociliary transport are essential defense mechanisms of the airways. Deviations in mucus composition and secretion can impede mucociliary transport and elicit airway obstruction. As such, mucus abnormalities are hallmark features of many respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Studying mucus composition and its physical properties has therefore been of significant interest both clinically and scientifically. Yet, measuring mucus production, output, composition and transport presents several challenges. Here we summarize and discuss the advantages and limitations of several techniques from five broadly characterized strategies used to measure mucus secretion, composition and mucociliary transport, with an emphasis on the gel-forming mucins. Further, we summarize advances in the field, as well as suggest potential areas of improvement moving forward.
Topics: Animals; Bronchoscopy; Humans; Mucins; Mucociliary Clearance; Mucus; Respiration Disorders
PubMed: 31752894
DOI: 10.1186/s12931-019-1239-z -
Respiratory Care Sep 2007Effective clearance of inhaled particles requires mucus production and continuous mucus transport from the lower airways to the oropharynx. Mucus production takes place... (Review)
Review
Effective clearance of inhaled particles requires mucus production and continuous mucus transport from the lower airways to the oropharynx. Mucus production takes place mainly in the peripheral airways. Mucus transport is achieved by the action of the ciliated cells that cover the inner surface of the airways (mucociliary transport) and by expiratory airflow. The capacity for mucociliary transport is highest in the peripheral airways, whereas the capacity for airflow transport is highest in the central airways. In patients with airways disease, mucociliary transport may be impaired and airflow transport may become the most important mucus transport mechanism.
Topics: Bronchi; Cough; Exhalation; Humans; Inhalation Exposure; Mucociliary Clearance; Mucus; Respiratory Mucosa
PubMed: 17716383
DOI: No ID Found -
Advanced Drug Delivery Reviews Mar 2019Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends... (Review)
Review
Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends to include therapeutic macromolecules and nanoparticles (NPs) through trapping of these particles. Mucus is not only a physical barrier that limiting particles movements based on their sizes but it selectively binds with particles through both hydrophilic and lipophilic interactions. Therefore, nano-carriers for mucosal delivery should be designed to eliminate entrapment by the mucus barrier. For this reason, different strategies have been approached for both solid nano-carriers and liquid core nano-carriers to synthesise muco-diffusive nano-carrier. Among these nano-strategies, Self-Emulsifying Drug Delivery System (SEDDS) was recognised as very promising nano-carrier for mucus delivery. The system was introduced to enhance the dissolution and bioavailability of orally administered insoluble drugs. SEDDS has shown high stability against intestinal enzymatic activity and more importantly, relatively rapid permeation characteristics across mucus barrier. The high diffusivity of SEDDS has been tested using various in vitro measurement techniques including both bulk and individual measurement of droplets diffusion within mucus. The selection and processing of an optimum in vitro technique is of great importance to avoid misinterpretation of the diffusivity of SEDDS through mucus barrier. In conclusion, SEDDS is a system with high capacity to diffuse through intestinal mucus even though this system has not been studied to the same extent as solid nano-carriers.
Topics: Animals; Diffusion; Drug Delivery Systems; Emulsions; Humans; Mucus; Nanotechnology; Permeability
PubMed: 30974131
DOI: 10.1016/j.addr.2019.04.001