Mucus gel layer

Atuma, C., Strugala, V., Allen, A., and Holm, L. (2001). The adherent gastrointestinal mucus gel layer Thickness and physical state in vivo. Am. ]. Physiol. Ser G. 280, G922-G929. 

Morini, G., Grandi, D., Gentili, S., Bertaccini, G., 1996b. Prevention by (R)-a-methylhistamine of ethanol-induced gastric mucosal lesions in rats importance of adherent mucus gel layer. ActaBio-Med. (Ateneo Parmense) 67, 71-78. 

In order to improve the mucosal absorption of poorly absorbed drugs such as peptides and proteins, newer delivery systems with higher mucoadhesive and permeation-enhancing polymers have been developed. While the first generation of mucoadhesive polymers provided adhesion to the mucus gel layer via secondary bonds, the new generation of mucoadhesive polymers is able to form covalent bonds with the mucous layer. The immobilization of thiol groups on mucoadhesive polymers results in thiolated polymers or thiomers that can form disulfide bonds with cysteine-rich subdomains of mucus glycoproteins [84,85]. 

Mucoadhesive polymers can be divided into non-covalent binding and covalent binding polymers. On the one hand the mechanism of mucoadhesion is based on hydrogen bonds, ionic interactions and van der Waal forces for non-covalent binding polymers, and on the other hand, on covalent bonds between the mucus and certain residues of the polymer. Moreover, physical interactions such as interpenetration of the polymer into the mucus gel layer entangle the polymer chains, which is strongly influenced by the swelling behaviour of the... 

The second challenge is the passage through the mucus gel layer. Gl-epithelia are covered by a mucus gel layer, which is 80-200 pm in thickness. The viscosity of mucus affects the diffusion barrier. The presence of sulfate and sialic acid moieties in mucus causes a negative net charge. Hence, the diffusion barrier is even more pronounced for cationic nucleic acid/polymer complexes, which undergo ionical immobilization on the mucus. 

Due to the turnover of the mucus gel layer of the mucus surface, which in some tissues such as the intestine is very fast, the adhesion of mucoadhesive devices of drug release is more difficult. This fact, along with the non-specificity of adhesion of these devices has caused this to be researched in the development of release systems that include lectins and lectin-like molecules, which can directly interact with the cellular membrane in such a way that a cytoadhesion independent of mucus turnover is produced. ... 

Mechanical Epithelial cell Epithelial mucus gel layer Peristalsis Gastric acid Bile salts... 

Szentkuti, L., light microscopical observations on luminally administered dyes, dextranes, nanospheres and microspheres in the preepi-thelial mucus gel layer of the rat distal colon. 

Figure 18.21 Schematic diagram representing the interpenetration between tethered chains and mucus gel layer [97],...

The capacity of pathogenic bacteria to adhere to mucosal membranes has been exploited in the modification of new mucoadhesive polymers. The ability of bacteria to adhere to a specific target is rooted from particular cell-surface components or appendages, known as fimbriae, which promote adhesion to other cells or inanimate surfaces. Fimbriae are extracellular, long thread-like protein polymers of bacteria that play a major role in many diseases. It has been reported that Escherichia coli adheres specifically to the lymphoid follicle epithelium of the ileal Peyer s patch in rabbits. Similarly, different staphylococci possess the ability to adhere specifically to the surface of mucus gel layers and not mucus-free surfaces. Thus, polymers have been modified by the attachment of these fimbriae to enhance mucoadhesion. An attachment protein derived from E. coli, K99-fimbriae, has been covalently attached to polyacrylic acid networks in an attempt to provide a novel polymer with enhanced adhesive properties (Figure 52.7). ... 

Mucoadhesion, defined as the ability to adhere to the mucus gel layer, is a key element in the design of polymer systems for specific applications. Mucus gel is composed of 95 % water and about 5 % mucus glicoproteins, called mucin, plus a number of minor components [47]. 

Atuma C, Strugala V, Allen A (2001) The adherent gastrointestinal mucus gel layer thickness and physical state in vivo Am J Physiol Gastrointest Liver Physiol 280 G922-G929. 

The small transport surface in the main airways (which could lead to the accumulation of secretions) is compensated in normal subjects by greater velocity related to higher ciliary beat frequency. The most important transport mechanism of mucus in the bronchial tree is mucociliary transport. This movement takes place by coordinated activity of cilia that cover the bronchial surface of the airways. Ciliated cells are found in the airways from the trachea to the terminal bronchioles. Each cell contains about 200 cilia, all of which end in little claws. The cilia beat in the direction of the oropharynx with a frequency of about 8 to 15 Hz. The claws of the cilia reach the mucus gel layer and push this layer towards the oropharynx. The recovery beat in the direction of the bronchioles takes place only in the periciliary sol layer. The cilia normally move the mucus at 1 mm/min in smaller airways and at up to 2 cm/min in the trachea (1,4,6). 

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