Mucoadhesive polymer, interpenetration

FIG. 1. Three stages in the interaction between a mucoadhesive polymer and mucin glycoprotein according to the interpenetration theory. 

Rossi et al. [30] evaluated rheologically mucins of different origin with polyacrylic acid and sodium carboxymethyl cellulose. The same group also reported a novel rheological approach based on a stationary viscoelastic test (creep test) to describe the interaction between mucoadhesive polymers and mucins [31,32]. Jabbari et al. [33] used attenuated total-reflection infrared spectroscopy to investigate the ehain interpenetration of polyaciylic acid in the mucin interface. 

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 hydrophilic groups on mucoadhesive polymers and the large amount of water associated with mucin present two possible adhesion mechanisms (i) hydrogen bonding and (ii) interpenetration of a swollen gel network with hydrated mucin. Many methods have been used for the assessment of bioadhesive properties, including fluorescent techniques and tensile tests. By using these methods, a number of natural and synthetic polymers have been discovered possessing mucoadhesive properties. 

Non-ionic polymers are less dependent on parameters such as pH levels and electrolyte concentration of the surrounding fluids. The main mechanism of mucoadhesion seems to be just physical by interpenetration and subsequent chain entanglement. Some of the polymers such as polyethylene oxide can additionally form hydrogen bonds, but still play only a minor role in macro-molecular drug delivery due to less pronounced mucoadhesive properties than the above-described charged polymers. 

The strength of mucoadhesion decreases with an increase in cross-linking as this leads to a decrease in the polymer s diffusion coefficient and chain segment flexibility and mobility (which in turn reduces interpenetration). 

FIGURE 52.4 Molecular model of chain interpenetration during mucoadhesion of a polymer (A) with the mucin (B). Three stages are distinguished in the process (a) contact, (b) interpenetration, and (c) interaction. (Reprinted from J. Contr. Release, 2, Peppas, N.A. and Buri, P.A., Snrface, interfacial and molecular aspects of polymer bioadhesion on soft tissues, 257-275. Copyright 1985, with permission from Elsevier.)... 

The interpenetration between the polymer chains and the mucin chains in the mucosa is believed to be the main physical mechanism for mucoadhesion, and together with the adsorption theory is the most accepted in the literature. This mechanism was first proposed in the polymer-polymer interface" " but was later applied to mucoadhesion due to the polymeric nature of mucin. Basically, during interpenetration the molecules of the mucoadhesive and the mucin molecules in the mucosa are brought into contact, and due to the concentration gradient the polymer chains penetrate into the mucin network with specific diffusion coefficients (Figure 52.4). 

There is no unified theory to explain the process of mucoadhesion. The total phenomenon of mucoadhesion is a combined result of all these theories. First, the polymer gets wet and swells (wetting theory) followed by the noncovalent (physical) bonds created within the mucus-polymer interface (electronic and adsorption theory). Then, the polymer and protein chains interpenetrate (diffusion theory) and entangle together to form further noncovalent (physical) and covalent... 

When macromolecular hydrocolloids with hydrophilic functional groups are placed in aqueous media, they swell and expand into a gel or network. Interpenetration and entanglement of this network with the mucin substrate can be partly responsible for the mucoadhesive properties. Therefore, mobility and flexibility of the polymer chains is a prerequisite for strong mucoadhesion. 

Fig. 1 Interpenetration between the gel polymer and mucous molecules during mucoadhesion.

Fig. 6.6 Polymer-mucous membrane chains interpenetration in mucoadhesion phenomena...

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