Mucoadhesive Hydrogel Research Articles

An investigation of the physical behaviour of moisture-activated mucoadhesive hydrogels upon contact with biological and non-biological substrates

The physical behaviour of moisture-activated mucoadhesive hydrogels in contact with a Plexiglas® plate or artificial mucin gels was investigated using an adapted tensile tester fitted with force and displacement transducers. Our study of the ‘Plexiglas®-hydrogel’ interface showed that the intrinsic mechanical response of most poly(acrylic acid) polymers is quite different from that exhibited by cellulose derivatives. The former exert an attractive interaction towards the substrate in contrast to the latter where the interaction is essentially repulsive. The interfacial forces developed by pure mucin were closely related to those of poly(acrylic acid) polymers. Similar results were observed when the Plexiglas® was replaced by artificial mucin gels. A correlation was found between the attractive force developed by poly(acrylic acid) hydrogels towards the inert substrate and their in vitro mucoadhesive joint strength. Therefore, a non-specific physical interaction occurs during the initial adhesive process, whatever the nature of the substrate. Besides the water absorption capacity and swelling properties of the candidate materials, it seems that their initial mucoadhesiveness depends more on their mechanical response to hydration and less on the extent of molecular interactions at the adhesive interface.

Visualization studies of the mucoadhesive interface

Aim of this study was to prove the occurrence of intermixing (“interpenetration”) at the interfacial zone between the mucoadhesive polymer Polycarbophil and intestinal mucus by (electron)-microscopical examination. As both phases are essentially hydrogels, various cryotechniques were tried to achieve dehydration of the samples without destroying the polymeric network structure of the native gels. Freeze fracture replication or sputter-coating of freeze-dried samples for transmission or scanning electron microscopy did not allow to identify the two hydrogel phases by characteristic network structures. Best results were obtained with plastic sections of freeze substituted samples. With light microscopy, mucus glycoproteins could be identified unambiguously by specific histochemical reactions. The mucoadhesive interface appeared as an irregular borderline with many coves and invaginations, but was sharp rather than hazy. There was no evidence for intermixing between mucus and mucoadhesive hydrogel to occur in the μ-range. Interpenetration of free polymer chain ends, however, may still be possible in the nm-range.

A new approach to study mucoadhesion: colloidal gold staining

A new in vitro method called “mucin-gold staining” was developed for the quantitative comparison of mucoadhesive properties of various hydrogels. The technique employs red colloidal gold particles which are stabilized by the adsorbed mucin molecules (mucin-gold conjugates). Upon interaction with mucin-gold conjugates, mucoadhesive hydrogels develop a red color on the surface. Thus, the mucoadhesive properties of hydrogels can be compared quantitatively by measuring the intensity of the red color. The pH-dependent stability of mucin-gold conjugates were examined and optimum conditions for mucin-gold staining were determined. The validity of the mucin-gold staining as a method to determine mucoadhesive property was tested using acrylic hydrogels of which mucoadhesive properties were well known. The potential applications and the advantages of this new in vitro technique are discussed.

Hydrogels for buccal drug delivery: properties relevant for muco-adhesion.

In order to develop a muco-adhesive hydrogel for buccal drug delivery it is necessary to understand fully the properties determining adhesiveness as well as mechanisms involved. In this study we measured glass transition temperatures, water contact angles and the peel- and shear detachment forces from porcine oral mucosa, of acrylic acid and butyl acrylate copolymers. The contact angle maximizes at 50% butyl acrylate content. The glass transition temperature decreases from 0% to 100% butyl acrylate. There seems to exist a certain combination of contact angle and glass transition temperature which is related to adhesiveness. This strongly suggests that, in order to obtain a muco-adhesive hydrogel, at least two properties have to be optimized: (1) the polarity of the polymer surface and (2) the molecular mobility of the polymer groups.