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Frontiers in Cellular and Infection... 2022The mucosal surfaces that form the boundary between the external environment and the underlying tissue are protected by a mucus barrier. Mucin glycoproteins, both... (Review)
Review
The mucosal surfaces that form the boundary between the external environment and the underlying tissue are protected by a mucus barrier. Mucin glycoproteins, both secreted and cell surface mucins, are the major components of the barrier. They can exclude pathogens and toxins while hosting the commensal bacteria. In this review, we highlight the dynamic function of the mucins and mucus during infection, how this mucosal barrier is regulated, and how pathogens have evolved mechanisms to evade this defence system.
Topics: Bacteria; Glycoproteins; Mucins; Mucous Membrane; Mucus
PubMed: 35774401
DOI: 10.3389/fcimb.2022.856962 -
European Respiratory Review : An... Jun 2010Mucus hypersecretion is a clinical feature of severe respiratory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Airway mucosal... (Review)
Review
Mucus hypersecretion is a clinical feature of severe respiratory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Airway mucosal infection and/or inflammation associated with these diseases often gives rise to inflammatory products, including neutrophil-derived DNA and filamentous actin, in addition to bacteria, apoptotic cells and cellular debris, that may collectively increase mucus production and viscosity. Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus hypersecretion is a clinical complication. The main purpose of mucoactive drugs is to increase the ability to expectorate sputum and/or decrease mucus hypersecretion. Many mucoactive drugs are currently available and can be classified according to their putative mechanism of action. Mucoactive medications include expectorants, mucoregulators, mucolytics and mucokinetics. By developing our understanding of the specific effects of mucoactive agents, we may result in improved therapeutic use of these drugs. The present review provides a summary of the most clinically relevant mucoactive drugs in addition to their potential mechanism of action.
Topics: Expectorants; Humans; Mucus; Pulmonary Disease, Chronic Obstructive
PubMed: 20956181
DOI: 10.1183/09059180.00003510 -
Cell Host & Microbe Feb 2016The interaction between respiratory pathogens and their hosts is complex and incompletely understood. This is particularly true when pathogens encounter the mucus layer... (Review)
Review
The interaction between respiratory pathogens and their hosts is complex and incompletely understood. This is particularly true when pathogens encounter the mucus layer covering the respiratory tract. The mucus layer provides an essential first host barrier to inhaled pathogens that can prevent pathogen invasion and subsequent infection. Respiratory mucus has numerous functions and interactions, both with the host and with pathogens. This review summarizes the current understanding of respiratory mucus and its interactions with the respiratory pathogens Pseudomonas aeruginosa, respiratory syncytial virus and influenza viruses, with particular focus on influenza virus transmissibility and host-range specificity. Based on current findings we propose that respiratory mucus represents an understudied host-restriction factor for influenza virus.
Topics: Animals; Host-Pathogen Interactions; Humans; Mucus; Pseudomonas aeruginosa; Respiratory Tract Infections; Virus Physiological Phenomena
PubMed: 26867175
DOI: 10.1016/j.chom.2016.01.001 -
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 -
Current Opinion in Biotechnology Aug 2018Mucus is a hydrogel that exhibits complex selective permeability, permitting the passage of some particles while restricting the passage of other particles including... (Review)
Review
Mucus is a hydrogel that exhibits complex selective permeability, permitting the passage of some particles while restricting the passage of other particles including important therapeutics. In this review, we discuss biochemical mechanisms underlying mucus penetration and mucus binding, emphasizing the importance of steric, electrostatic, and hydrophobic interactions. We discuss emerging techniques for engineering nanoparticle surface chemistries for mucus penetration as well as recent advances in tuning mucus interactions with small molecule, peptide, or protein therapeutics. Finally, we highlight recent work suggesting that mucus permeability can serve as a biomarker for disease and physiological states such as pregnancy.
Topics: Animals; Disease; Health; Humans; Mucus; Permeability; Tissue Engineering
PubMed: 29674157
DOI: 10.1016/j.copbio.2018.03.010 -
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 -
Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions.Journal of Ocular Pharmacology and... 2020The ocular surface is naturally covered with a layer of mucus. Along with other functions, this mucus layer serves to trap and eliminate foreign substances, such as... (Review)
Review
The ocular surface is naturally covered with a layer of mucus. Along with other functions, this mucus layer serves to trap and eliminate foreign substances, such as allergens, pathogens, and debris. In playing this pivotal role, mucus can also hinder topical delivery of therapeutics to the eye. Recent studies provide evidence that drugs formulated as traditional micro- or nanoparticles are susceptible to entrapment and rapid clearance by ocular mucus. Mucus-penetrating particles (MPPs) is a nanoparticle technology that emerged over the past decade. With a muco-inert surface and a particle size smaller than the mucus mesh size, MPPs can diffuse in mucus essentially freely. Preclinical studies have shown that, compared with particles lacking the mucus-penetrating attributes, MPPs can improve the uniformity of drug particle distribution on mucosal surfaces and enhance drug delivery to ocular tissues.
Topics: Administration, Topical; Animals; Drug Compounding; Drug Delivery Systems; Humans; Mice; Models, Animal; Mucus; Nanoparticles; Ocular Physiological Phenomena; Surface Properties
PubMed: 32667250
DOI: 10.1089/jop.2020.0022 -
Proceedings of the National Academy of... Sep 2008We normally live in symbiosis with approximately 10(13) bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is...
We normally live in symbiosis with approximately 10(13) bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is limited understanding of the structure, function, and properties of intestinal mucus. We now demonstrate that the mouse colonic mucus consists of two layers extending 150 mum above the epithelial cells. Proteomics revealed that both of these layers have similar protein composition, with the large gel-forming mucin Muc2 as the major structural component. The inner layer is densely packed, firmly attached to the epithelium, and devoid of bacteria. In contrast, the outer layer is movable, has an expanded volume due to proteolytic cleavages of the Muc2 mucin, and is colonized by bacteria. Muc2(-/-) mice have bacteria in direct contact with the epithelial cells and far down in the crypts, explaining the inflammation and cancer development observed in these animals. These findings show that the Muc2 mucin can build a mucus barrier that separates bacteria from the colon epithelia and suggest that defects in this mucus can cause colon inflammation.
Topics: Animals; Colitis; Colon; Intestinal Mucosa; Mice; Mice, Mutant Strains; Mucin-2; Mucins; Mucus; Rats; Rats, Sprague-Dawley; Symbiosis
PubMed: 18806221
DOI: 10.1073/pnas.0803124105 -
Advanced Drug Delivery Reviews Feb 2009Mucus is a complex biological material that lubricates and protects the human lungs, gastrointestinal (GI) tract, vagina, eyes, and other moist mucosal surfaces. Mucus... (Review)
Review
Mucus is a complex biological material that lubricates and protects the human lungs, gastrointestinal (GI) tract, vagina, eyes, and other moist mucosal surfaces. Mucus serves as a physical barrier against foreign particles, including toxins, pathogens, and environmental ultrafine particles, while allowing rapid passage of selected gases, ions, nutrients, and many proteins. Its selective barrier properties are precisely regulated at the biochemical level across vastly different length scales. At the macroscale, mucus behaves as a non-Newtonian gel, distinguished from classical solids and liquids by its response to shear rate and shear stress, while, at the nanoscale, it behaves as a low viscosity fluid. Advances in the rheological characterization of mucus from the macroscopic to nanoscopic levels have contributed critical understanding to mucus physiology, disease pathology, and the development of drug delivery systems designed for use at mucosal surfaces. This article reviews the biochemistry that governs mucus rheology, the macro- and microrheology of human and laboratory animal mucus, rheological techniques applied to mucus, and the importance of an improved understanding of the physical properties of mucus to advancing the field of drug and gene delivery.
Topics: Animals; Drug Delivery Systems; Humans; Mucous Membrane; Mucus; Rheology
PubMed: 19166889
DOI: 10.1016/j.addr.2008.09.012