Hydrogels as novel substitutes of animal tissues for investigation of mucoadhesive properties of polymeric dosage forms

Mucous membranes line body cavities that are exposed to the external environment such as the respiratory tract, the gastrointestinal tract, the nostrils and the mouth. Mucus, secreted by glands and cells associated with the membrane, is a viscous yet slippery substance that mainly contains mucin, water and inorganic salts whose purpose is to act as a protective lubricant for the membrane. This viscous lining offers potential to adhere a pharmaceutical formulation to the membrane to allow prolonged drug delivery at a particular site; mucoadhesion can thus be defined as the adhesion of a formulation to a mucous membrane. In developing mucoadhesive drug delivery systems, the vast majority of researchers use animal tissue as a mimic for the human membranes. Over 60 % of research articles published in this area used animals which were sacrificed before or after the experiments. Also no standardised approach to using the animal membranes has been reported, and much work conflicts due the variations in animal model selected meaning the results from different laboratories may not be correlated. In this project, we will develop a standardised alternative synthetic 'mucous membrane mimic' which will be highly controlled and reproducible by forming hydrogel based on sugar based polymers. These glyco-polymers resemble the mucin and other components found in natural mucus and hydrogels, which are water swellable polymers that include a large fraction of water yet remain in a gel state, have been used to mimic other biological tissues. This project will synthesise a range of glycol-polymer hydrogels whose mucoadhesive properties will be validated by correlating adhesion of various formulations to the model in comparison with adhesion to pig mucosal membranes. By generating a standardised and validated model system, we will also be able to further investigate the mechanisms of mucoadhesion whilst offering a viable alternative to animal testing of these formulations.

Mucoadhesion is defined as interfacial force interactions between polymeric materials and mucosal tissues. In developing mucoadhesive drug delivery systems, the vast majority of researchers use animal tissue as a mimic for the human membranes. Over 60 % of research articles published in this area used animals which were sacrificed before or after the experiments. Also no standardised approach to using the animal membranes has been reported, and much work conflicts due to the variations in animal model selected meaning the results from different laboratories may not be correlated. This project will develop novel hydrogel materials to mimic the properties of mucosal membranes which can be used as substrates for examining mucoadhesive properties of new polymeric dosage forms in place of animal tissues. The hydrogels will be based on synthetic glycopolymers, which are polymers containing sugar moieties as pendant groups. To generate a logical series of mucous membrane mimics the gluco-monomer will be copolymerised with the monomers having different functionalities. These hydrogels will help to reduce the use of living animals when developing new mucoadhesive pharmaceutical formulations. Also, the use of hydrogels will provide a new standard test methodology to measure the mucoadhesive properties of dosage forms, which will improve the reliability, reproducibility and comparability of the research results. The information obtained as a result of this research will also help in further understanding of mucoadhesion phenomenon.