Wetting theory: Wetting is the oldest and most prevalent theory of adhesion. The adhesive components in a liquid solution anchor themselves in irregularities on the substrate and eventually harden, providing sites on which to adhere. Surface tension effects restrict the movement of the adhesive along the surface of the substrate, and is related to the thermodynamic work of adhesion by Dupre's Equation. Measuring the affinity of the adhesive for the substrate is performed by determining the contact angle. Contact angles closer to zero indicate a more wettable interaction, and those interactions have a greater spreadability.
Adsorption theory: Adsorption is another widely accepted theory, where adhesion between the substrate and adhesive is due to primary and secondary bonding. The primary bonds are due to chemisorption, and result in comparatively long lasting covalent and non-covalent bonds. Among covalent bonds disulfide bonds are likely most important. Thiolated polymers – designated thiomers – are mucoadhesive polymers that can form disulfide bonds with cysteine-rich subdomains of mucus glycoproteins. Recently several new classes of polymers have been developed that are capable of forming covalent bonds with mucosal surfaces similarly to thiomers. These polymers have acryloyl, methacryloyl, maleimide, boronate and N‐hydroxy (sulfo) succinimide ester groups in their structure. Among non-covalent bonds likely ionic interactions such as interactions of mucoadhesive chitosans with the anionically charged mucus  and Hydrogen bonding are most important. The secondary bonds include weak Van Der Waals forces, and interactions between hydrophobic substructure.
Diffusion theory: The mechanism for diffusion involves polymer and mucin chains from the adhesive penetrating the matrix of the substrate and forming a semipermanent bond. As the similarities between the adhesive and the substrate increase, so does the degree of mucoadhesion. The bond strength increases with the degree of penetration, increasing the adhesion strength. The penetration rate is determined by the diffusion coefficient, the degree of flexibility of the adsorbate chains, mobility and contact time. The diffusion mechanism itself is affected by the length of the molecular chains being implanted and cross-linking density, and is driven by a concentration gradient.
Electrostatic theory: is an electrostatic process involving the transfer of electrons across the interface between the substrate and adhesive. The net result is the formation of a double layer of charges that are attracted to each other due to balancing of the Fermi layers, and therefore cause adhesion. This theory only works given the assumption that the substrate and adhesive have different electrostatic surface characteristics.
 Fracture theory: Fracture theory is the major mechanism by which to determine the mechanical strength of a particular mucoadhesive, and describes the force necessary to separate the two materials after mucoadhesion has occurred. Ultimate tensile strength is determined by the separating force and the total surface area of the adhesion, and failure generally occurs in one of the surfaces rather than at the interface. Since the fracture theory only deals with the separation force, the diffusion and penetration of polymers is not accounted for in this mechanism.