Atomic force microscopy of gastric mucin and chitosan mucoadhesive systems

Abstract

Atomic force microscopy has been utilized to probe, at a molecular level, the interaction between purified pig gastric mucin (PGM) and a mucoadhesive cationic polymer, chitosan (sea cure 210+), with a low degree (approx. 11%) of acetylation. Images were produced detailing the structures of both PGM and chitosan in 0.1 M acetate buffer (pH 4.5), followed by the complex of the two structures in the same buffer. PGM in 0.1 M acetate buffer revealed long linear filamentous structures, consistent with earlier electron microscopy and scanning tunnelling micoscopy studies. The chitosan molecules also adopted a linear conformation in the same buffer, although with a smaller average length and diameter. They appeared to adopt a stiff-coil conformation consistent with earlier hydrodynamic measurements. The complexes formed after mixing PGM and chitosan together revealed large aggregates. In 0.1 M ionic strength buffer they were of the order of 0.7 microm in diameter, consistent with previous electron microscopy studies. The effect of ionic strength of the buffer on the structure of the complex was also studied and, together with molecular hydrodynamic data, demonstrates that the interaction is principally electrostatic in nature.

In Vitro and ex Vivo Intestinal Tissue Models to Measure Mucoadhesion of Poly (Methacrylate) and N-Trimethylated Chitosan Polymers

“…While it has been shown that electrostatic interaction is a major factor in the adhesion of cationic chitosan to purified anionic pig mucin (36), charge-based interactions of polymers with mucus remains poorly understood. The main adhesive interactions between adhesive polymers and mucus occur via covalent bonding, hydrogen bonding and electrostatic and hydrophobic interactions or a combination of these (41).…”

“…Notable targets for tensile tests have included isolated thawed bovine duodenal (32), porcine esophageal (34), and rat intestinal tissue (35). Recently, atomic force microscopy has been used to quantitatively measure and image polymer interaction with mucin (36), although this technique has yet to be applied to mucus-producing epithelia. In addition, mucoadhesion of microparticles comprising fluorescent polycarbophil to isolated fresh porcine intestinal mucosa has recently been assessed in a flow-through system using phosphate buffer (37).…”

Progress Towards a Needle-Free Hepatitis B Vaccine

“…This has been one of the main reasons for its wide applicability to the encapsulation of different molecules such as DNA and antigens. Chitosan is also known to be mucoadhesive (37). At physiological pH, sialic acid molecules present in mucus have a negative charge, and, as a consequence, positively charged chitosan exerts strong electrostatic interaction with them.…”

“…3c) and loaded them with DNA containing pRc/ CMV-HBs(S). Chitosan is known for its mucoadhesive properties (37); thus, the addition of this polymer to the formulation is advantageous for creating an intranasal formulation with prolonged local retention. To test the immunological response, mice were immunized with glycol chitosan-coated liposomes loaded with DNA, as well as with naked DNA (i.n.…”

Surface Characterisation of Bioadhesive PLGA/Chitosan Microparticles Produced by Supercritical Fluid Technology

“…The particles were either post coated with chitosan, or chitosan was introduced in the particle production process, to achieve the partial or complete mucoadhesive chitosan coating of the particles. The ability of chitosan to form strong electrostatic interaction with mucus or a negatively charged mucosal surface has been described by different authors (29)(30)(31). It was found that chitosan could provide longer residence times for a dosage form on mucosal tissues and rapid absorption of the drug from the bioadhesive delivery system, avoiding its dilution or degradation (27,32).…”