An in vitro assessment of mucus/mucoadhesive interactions

Abstract

One proposed mechanism of mucoadhesion involves the interpenetration of the mucus/mucoadhesive molecules, followed by the formation of secondary chemical bonds. In this study the nature of interactions between the mucus gel and the mucoadhesive macromolecule was investigated. A logarithmic frequency sweep between 10 and 0.002 Hz was used to investigate the nature of interactions between homogenised mucus gel and the model mucoadhesive Carbopol 934P (C934) at pH 6.2. The rheogram obtained was found to be intermediate between a physically entangled system and a cross-linked system, and was found to closely resemble that of a mixture of mucus glycoprotein (major structure forming component of the mucus gel) and C934 at pH 6.2. Furthermore, it was found that the addition of the hydrogen bond breaking agents urea and potassium thiocyanate (KCNS) to a mixture of homogenised mucus/C934 at pH 6.2 resulted in a reduction in the G′ (storage modulus) as well as the G′(loss modulus) of the mixture. The addition of the model monosaccharides l-fucose and d-galacturonic acid to the mucoadhesive poly(acrylic acid) (paa) shifted the paa carboxylic acid signals upfield and downfield, respectively, when tested using 13C-NMR. The addition of urea and KCNS to the l-fucose/paa as well as the paa/water control mixtures at pH 6.2 resulted in a positional change in the chemical shift of the paa carboxylic acid signals, when examined using 13C-NMR. Finally, the incorporation of urea into 50 mg C934 or poly(ethylene oxide) discs resulted in a reduction in their mucoadhesive strength in vitro. It is concluded that the mucoadhesive polymer could interact with the mucus glycoproteins by forming physical entanglements followed by hydrogen bonds with sugar residues on the oligosaccharide chains, resulting in the formation of a strengthened mucus gel network, which allows the mucoadhesive system to remain adhesive for an extended period of time. Disruption of hydrogen bonds could substantially reduce the adhesive strength of a mucoadhesive system, suggesting the importance of these bonds in mucoadhesion.