Mucoadhesion

Mucoadhesion involves several types of bonding mechanisms, and it is the interaction between each process that allows for the adhesive process. The major categories are wetting theory, adsorption theory, diffusion theory, electrostatic theory, and fracture theory. Specific processes include mechanical interlocking, electrostatic, diffusion interpenetration, adsorption and fracture processes. == Bonding mechanisms ==

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. 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. == Stages of mucoadhesive process ==

The mucoadhesive process will differ greatly depending on the surface and properties of the adhesive. However, two general steps of the process have been identified: the contact stage and the consolidation stage. This mixture of formulation and mucus can increase contact time with the mucous membrane, leading to the consolidation of the adhesive bond. However, the dehydration theory does not apply to solid formulations or highly hydrated forms. == Mucoadhesives in drug delivery ==

Depending on the dosage form and route of administration, mucoadhesives may be used for either local or systemic drug delivery. An overview on the mucoadhesive properties of mucoadhesives is provided by Vjera Grabovac and Andreas Bernkop-Schnürch. The bioavailability of such drugs is affected by many factors unique to each route of application. In general, mucoadhesives work to increase the contact time at these sites, prolonging the residence time and maintaining an effective release rate. These polymeric coatings may be applied to a wide variety of liquid and solid dosages, each specially suited for the route of administration. Dosage Forms Tablets Tablets are small, solid dosages suitable for the use of mucoadhesive coatings. The coating may be formulated to adhere to a specific mucosa, enabling both systemic and targeted local administration. Tablets are generally taken enterally, as the size and stiffness of the form results in poor patient compliance when administered through other routes. A significant advancement in this area is the development of anhydrous (water-free) self-emulsifying bases. These bases remain stable during storage but transform into a mucoadhesive emulsion upon contact with physiological fluids. This mechanism significantly reduces leakage and prolongs the drug's contact time with the tissue, making them ideal for vaginal or buccal delivery. Furthermore, anhydrous systems can accommodate a broader range of both hydrophilic and lipophilic active pharmaceutical ingredients (APIs) while offering improved chemical stability compared to traditional aqueous creams. Gels As a liquid or semisolid dosage, gels are typically used where a solid form would affect the patient's comfort. As a trade-off, conventional gels have poor retention rates. This results in unpredictable losses of the drug, as the non-solid dosage is unable to maintain its position at the site of administration. Mucoadhesives increase retention by dynamically increasing the viscosity of the gel after application. This allows the gel to effectively administer the drug at the local site while maintaining the comfort of the patient. == Routes of Administration ==

Oromucosal With a 0.1-0.7 mm thick mucus layer, the oral cavity serves as an important route of administration for mucoadhesive dosages. Permeation sites can be separated into two groups: sublingual and buccal, in which the former is much more permeable than the latter. However, the sublingual mucosa also produces more saliva, resulting in relatively low retention rates. Thus, sublingual mucosa is preferable for rapid onset and short duration treatments, while the buccal mucosa is more appropriate for longer dosage and onset times. Because of this dichotomy, the oral cavity is suitable for both local and systemic administration. Some common dosage forms for the oral cavity include gels, ointments, patches, and tablets. Depending on the dosage form, some drug loss can occur due to swallowing of saliva. This can be minimized by layering the side of the dosage facing the oral cavity with an impermeable coating(,) commonly seen in patches. Nasal With an active surface area of 160 cm2, the nasal cavity is another noteworthy route of mucoadhesive administration. Due to the sweeping motion of the cilia that lines the mucosa, nasal mucus has a quick turnover of 10 to 15 minutes. Because of this, the nasal cavity is most suitable for rapid, local medicinal dosages. Additionally, its close proximity to the blood–brain barrier makes it a convenient route for administering specialized drugs to the central nervous system. Gels, solutions, and aerosols are common dosage forms in the nasal cavity. However, recent research into particles and microspheres have shown increased bioavailability over non-solid forms of medicine largely due to the use of mucoadhesives. Ocular Within the eye, it is difficult to achieve therapeutic concentrations through systemic administration. Often, other parts of the body will reach toxic levels of the medication before the eye reaches the treatment concentration. Consequently, direct administration through the fibrous tunic is common. This is made difficult due to the numerous defense mechanisms in place, such as blinking, tear production, and the tightness of the corneal epithelium. Estimates put tear turnover rates at 5 minutes, meaning most conventional drugs are not retained for long periods of time. Mucoadhesives increase retention rates, either by enhancing the viscosity or bonding directly to one of the mucosae surrounding the eye. Intravesical Intravesical drug administration is the delivery of pharmaceuticals to the urinary bladder through a catheter. This route of administration is used for the therapy of bladder cancer and interstitial cystitis. The retention of dosage forms in the bladder is relatively poor, which is related to the need for a periodical urine voiding. Some mucoadhesive materials are able to stick to mucosal lining in the bladder, resist urine wash out effects and provide a sustained drug delivery. == See also ==