Mucus bed thickness can change from 50-450 Aµm in the tummy to less than 1 Aµm in the unwritten cavity21. Mucus contains high molecular weight glycoprotein macromolecular component ( 0.2 and 10 million Dalton ) called as mucin. Mucin contains one or more spheres which are extremely glycosylated. The glycosylated spheres are enriched in serine and threonine residues which serve as grounding points for oligosaccharide side ironss. These O-linked oligosaccharide side ironss are complex both in footings of composing and length22. Mucin contains 68 and 81 % by weight fraction carbohydrate23. Mucin besides contains “ bare spheres ” which are present in the N-terminal and C-terminal portion of the protein, somewhat glycosylated or not glycosylated and copiously contains cysteine residues. The cysteine residues can organize intermolecular bonds24.

The glycosylated parts of mucin interact favourably with H2O and coerce the molecule to an drawn-out random spiral conformation, and the high molecular weight enables single mucin molecules to overlap and mire at comparatively low concentrations. These features are ideal with regard to the formation of hydrogel and probes have shown that reconstructed mucose gels from mucin have similar rheological belongingss as native mucose gels at physiological concentrations25.

Mucins are responsible for the viscoelastic belongingss of the mucous secretion secernments. Mucins are negatively charged molecules because of the presence of sialic acid and sulphated sugars residues on their surfaces. This produces attractive force forces between mucin and positively charged drug bearers in bringing system26. Therefore adhesive belongingss of mucin generate acute involvement in the development of gastro recollective drug bringing systems through the usage of bio/mucoadhesive polymers27.

1.4 Mechanisms and theories of mucoadhesion

The binding of polymers to the mucin epithelial surface can be studied through28-29 hydration mediated adhesion, receptor mediated adhesion and bonding mediated adhesion. Hydration mediated adhesion is produced when hydrophilic polymers tend to absorb big sum of H2O and go gluey, thereby geting mucoadhesive belongingss. Receptor mediated adhesion occurs when polymers bind to specific receptor sites on the surface of cells which enhances the stomachic keeping of dose signifiers. Plant lectins e.g. tomato lectins interact specifically with the sugar groups present in mucous secretion or on the glycocalyx. Bonding mediated adhesion occurs when the adhesion of polymers to a mucous secretion or epithelial cell surface involves physical bonding and chemical bonding. Physical bonds can ensue from the interpolation of the adhesive stuff into the crannies or creases of the mucous membrane. Chemical bonds may be either covalent ( primary ) or ionic ( secondary ) in nature. Secondary chemical bonds consist of new wave der Waals ‘ interactions and stronger specific interactions such as H bonds. The hydrophilic functional groups responsible for organizing H bonds are the hydroxyl and carboxylic groups.

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1.4.1 Stairss of Mucoadhesion

Weting and swelling is subjected to distributing of the polymer over mucosal membrane in order to develop an confidant contact with the substrate. The constituents available within the polymers have an affinity for H2O which leads puffiness of polymers.

Mucoadhesive bond formation is subjected to mucoadhesive bond formation between the mucoadhesive polymer ironss and the mucosal polymer ironss ( glycoproteins ) where they intermingle and entangle to organize semi permeable adhesive bonds. The strength of these bonds depends on the grade of incursion between the two polymer groups. In order to organize strong adhesive bonds, one polymer group must be soluble in the other and both polymer types must be of similar chemical construction.

Formation of weak chemical bonds between the embroiled polymer ironss subjected to the formation of weak chemical bonds between the embroiled polymer ironss. The types of adhering formed between the ironss include primary bonds such as covalent bonds and weaker secondary interactions such as new wave der Waals ‘ Interactions and H bonds. Both primary and secondary bonds are exploited in the industry of mucoadhesive preparations in which strong adhesions between polymers are formed.

Adhesion of drug bringing system onto mucose membrane can be affected by the mucociliary clearance system. It is a natural defence mechanism of the organic structure against the deposition of substances onto the mucose membrane which can besides take the drug bringing system. Therefore, it is possible to retain the bringing system at the site of action and to let the drug to absorb at specific site or tissue, by utilizing mucoadhesive polymers. Other advantage associated with the development of drawn-out release mucoadhesive drug bringing systems is to diminish the drug disposal frequence and to increase the patient conformity to the therapy6.

1.4.2 The mucoadhesive/mucosa interaction

Mucoadhesive are man-made or natural polymer, which interact with the mucous secretion bed covering the mucosal epithelial surface, and mucin molecules representing a major portion of mucus12, 21, 30, 31. For adhesion to happen, molecules must bond across the interface. These bonds can originate in the undermentioned manner.

Ionic bonds-where two oppositely charged ions attract each other via electrostatic interactions to organize a strong bond ( e.g. in a salt crystal ) .

Covalent bonds-where negatrons are shared, in braces, between the bonded atoms in order to make full the orbitals in both. These are besides strong bonds.

Hydrogen bonds-here a H atom, when covalently bonded to electronegative atoms such as O, F or N, carries a little positive charge and is hence is attracted to other negatively charged atoms. The H can hence be thought of as being shared, and the bond formed is by and large weaker than ionic or covalent bonds.

Van der Waals ‘ bonds-these are some of the weakest signifiers of interaction that arise from dipole-dipole and dipole-induced dipole attractive forces in polar molecules, and scattering forces with non-polar substances.

Hydrophobic bonds-more accurately described as the hydrophobic consequence, these are indirect bonds ( such groups merely appear to be attracted to each other ) that occur when non-polar groups are present in an aqueous solution. Water molecules next to non-polar groups form H bonded constructions, which lowers the system information. There is hence an addition in the inclination of non-polar groups to tie in with each other to minimise this consequence.

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