The goal of this study was to generate a new mucoadhesive carbohydrate-based delivery system composed of alginate (Alg) backbone covalently attached to polyethylene glycol (PEG) modified with a unique functional end-group (maleimide). The immobilization of PEG-maleimide chains significantly improved the mucoadhesion properties attributed to thioether bonds creation via Michael-type addition and hydrogen bonding with the mucus glycoproteins. Mucoadhesion studies using tensile and rotating cylinder assays revealed a 3.6-fold enhanced detachment force and a 2.8-fold enhanced retention time compared to the unmodified polymer, respectively. Additional indirect studies confirmed the presence of polymer-mucus glycoproteins interactions.
Drug release experiments were used to evaluate the release profiles from Alg-PEG-maleimide tablets in comparison to Alg and Alg-SH tablets. Viability studies of normal human dermal fibroblasts cells depicted the non-toxic nature of Alg-PEG-maleimide. Overall, our studies disclose that PEG-maleimide substitutions on other biocompatible polymers can lead to the development of useful biomaterials for diverse biomedical applications.