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The Journal of Allergy and Clinical... Mar 1984
Review
Topics: Adrenal Cortex Hormones; Atropine; Bronchi; Glycoproteins; Humans; Lung Diseases, Obstructive; Mucous Membrane; Mucus; Trachea
PubMed: 6366031
DOI: 10.1016/0091-6749(84)90403-2 -
Advanced Materials (Deerfield Beach,... Jul 2012A method that could provide more uniform and longer-lasting drug and gene delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of... (Review)
Review
A method that could provide more uniform and longer-lasting drug and gene delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections, cystic fibrosis, chronic rhinosinusitis, inflammatory bowel disease, and glaucoma to name a few. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. This article discusses the recent development of the “mucuspenetrating particle” or “MPP” nanotechnology, and how it has been used to both enhance understanding of the nanoscale barrier properties of human mucus secretions, and to achieve more uniform and longer-lasting drug delivery to mucosal tissues following topical administration. Drug loaded MPPs possess non-adhesive coatings that allow them to rapidly penetrate mucus layers through openings in the mucus mesh at rates nearly as fast as they would penetrate pure water. Critically, MPPs allow enhanced drug and gene delivery to mucosal tissues without diminishing the protective function of mucus. Recent progress in the development of MPPs as a biophysical tool to probe the length-scale dependent rheological properties of mucosal secretions and as a method for drug and gene delivery is highlighted.
Topics: Administration, Topical; Animals; Biophysical Phenomena; Drug Delivery Systems; Gene Transfer Techniques; Humans; Mucus; Nanoparticles; Nanotechnology
PubMed: 22988559
DOI: 10.1002/adma.201201800 -
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 -
Archives of Pharmacal Research Dec 2002The airway surface liquid (ASL), often referred to as mucus, is a thin layer of fluid covering the luminal surface of the airway. The major function of mucus is to... (Review)
Review
The airway surface liquid (ASL), often referred to as mucus, is a thin layer of fluid covering the luminal surface of the airway. The major function of mucus is to protect the lung through mucociliary clearance against foreign particles and chemicals entering the lung. The mucus is comprised of water, ions, and various kinds of macromolecules some of which possess the protective functions such as anti-microbial, anti-protease, and anti-oxidant activity. Mucus glycoproteins or mucins are mainly responsible for the viscoelastic property of mucus, which is crucial for the effective mucociliary clearance. There are at least eight mucin genes identified in the human airways, which will potentially generate various kinds of mucin molecules. At present, neither the exact structures of mucin proteins nor their regulation are understood although it seems likely that different types of mucins are involved in different functions and might also be associated with certain airway diseases. The fact that mucins are tightly associated with various macromolecules present in ASL seems to suggest that the defensive role of ASL is determined not only by these individual components but rather by a combination of these components. Collectively, mucins in ASL may be compared to aircraft carriers carrying various types of weapons in defense of airbome enemies.
Topics: Animals; Humans; Lung; Mucins; Mucociliary Clearance; Mucus
PubMed: 12510824
DOI: 10.1007/BF02976990 -
Paediatric Respiratory Reviews 2006
Review
Topics: Cough; Humans; Mucociliary Clearance; Mucus; Sputum; Viscosity
PubMed: 16798569
DOI: 10.1016/j.prrv.2006.04.199 -
ACS Biomaterials Science & Engineering Jun 2023The gastrointestinal mucus layer plays a significant role in maintaining gut homeostasis and health, offering protective capacities against the absorption of harmful... (Review)
Review
The gastrointestinal mucus layer plays a significant role in maintaining gut homeostasis and health, offering protective capacities against the absorption of harmful pathogens as well as commensal gut bacteria and buffering stomach acid to protect the underlying epithelium. Despite this, the mucus barrier is often overlooked during preclinical pharmaceutical development and may pose a significant absorption barrier to high molecular weight or lipophilic drug species. The complex chemical and physical nature of the dynamic mucus layer has proven problematic to reliably replicate in a laboratory setting, leading to the development of multiple mucus models with varying complexity and predictive capacity. This, coupled with the wide range of analysis methods available, has led to a plethora of possible approaches to quantifying mucus permeation; however, the field remains significantly under-represented in biomedical research. For this reason, the development of a concise collation of the available approaches to mucus permeation is essential. In this review, we explore widely utilized mucus mimics ranging in complexity from simple mucin solutions to native mucus preparations for their predictive capacity in mucus permeation analysis. Furthermore, we highlight the diverse range of laboratory-based models available for the analysis of mucus interaction and permeability with a specific focus on , , and models. Finally, we highlight the predictive capacity of these models in correlation with pharmacokinetic data. This review provides a comprehensive and critical overview of the available technologies to analyze mucus permeation, facilitating the efficient selection of appropriate tools for further advancement in oral drug delivery.
Topics: Pharmaceutical Preparations; Permeability; Mucus; Drug Delivery Systems; Bacteria
PubMed: 34784462
DOI: 10.1021/acsbiomaterials.1c00814 -
Veterinary Microbiology Jun 2014Fish are always in intimate contact with their environment; therefore they are permanently exposed to very vary external hazards (e.g. aerobic and anaerobic bacteria,... (Review)
Review
Fish are always in intimate contact with their environment; therefore they are permanently exposed to very vary external hazards (e.g. aerobic and anaerobic bacteria, viruses, parasites, pollutants). To fight off pathogenic microorganisms, the epidermis and its secretion, the mucus acts as a barrier between the fish and the environment. Fish are surrounded by a continuous layer of mucus which is the first physical, chemical and biological barrier from infection and the first site of interaction between fish's skin cells and pathogens. The mucus composition is very complex and includes numerous antibacterial factors secreted by fish's skin cells, such as immunoglobulins, agglutinins, lectins, lysins and lysozymes. These factors have a very important role to discriminate between pathogenic and commensal microorganisms and to protect fish from invading pathogens. Furthermore, the skin mucus represents an important portal of entry of pathogens since it induces the development of biofilms, and represents a favorable microenvironment for bacteria, the main disease agents for fish. The purpose of this review is to summarize the current knowledge of the interaction between bacteria and fish skin mucus, the adhesion mechanisms of pathogens and the major factors influencing pathogen adhesion to mucus. The better knowledge of the interaction between fish and their environment could inspire other new perspectives to study as well as to exploit the mucus properties for different purposes.
Topics: Animals; Bacterial Adhesion; Bacterial Physiological Phenomena; Fishes; Mucus; Skin
PubMed: 24709124
DOI: 10.1016/j.vetmic.2014.03.008 -
Advanced Drug Delivery Reviews Jan 2018Many drug molecules possess inadequate physical-chemical characteristics that prevent to surpass the viscous mucus layer present in the surface of mucosal tissues. Due... (Review)
Review
Many drug molecules possess inadequate physical-chemical characteristics that prevent to surpass the viscous mucus layer present in the surface of mucosal tissues. Due to mucus protective role and its fast turnover, these drug molecules end up being removed from the body before being absorbed and, thus, before exerting any physiologic affect. Envisaging a better pharmacokinetics profile, chemical modifications, to render drug a more mucopenetrating character, have been introduced to drug molecules backbone towards more effective therapies. Mucus penetration increases when drug molecules are provided with net-neutral charge, when they are conjugated with mucolytic agents and through modifications that makes them resistant to enzymes present in mucus, with the overall increase of their hydrophilicity and the decrease of their molecular weight. All of these characteristics act as a whole and influence each other so they must be well thought when drug molecules are being designed for mucosal delivery.
Topics: Animals; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Weight; Mucus; Pharmaceutical Preparations
PubMed: 28964880
DOI: 10.1016/j.addr.2017.09.020 -
The New England Journal of Medicine Jun 2021
Topics: Crystallization; Humans; Mucus; Nasal Mucosa
PubMed: 34133877
DOI: 10.1056/NEJMicm2034441 -
Advanced Drug Delivery Reviews Jan 2018Nanoparticulate drug delivery systems (nDDS) offer a variety of options when it comes to routes of administration. One possible path is crossing mucosal barriers, such... (Review)
Review
Nanoparticulate drug delivery systems (nDDS) offer a variety of options when it comes to routes of administration. One possible path is crossing mucosal barriers, such as in the airways and in the GI tract, for systemic distribution or local treatment. The main challenge with this administration route is that the size and surface properties of the nanoparticles, as opposed to small molecular drugs, very often results in mucosal capture, immobilization and removal, which in turn results in a very low bioavailability. Strategies to overcome this challenge do exist, like surface 'stealth' modification with PEG. Here we review an alternative or supplemental strategy, co-association of mucus modulating agents with the nDDS to improve bioavailability, where the nDDS may be surface modified or unmodified. This contribution presents some examples on how possible co-association systems may be achieved, using currently marketed mucolytic drugs, alternative formulations or novel agents.
Topics: Animals; Drug Delivery Systems; Humans; Mucus; Nanoparticles; Small Molecule Libraries
PubMed: 29307632
DOI: 10.1016/j.addr.2018.01.001