Development of maleimide-modified poly(N-(2-hydroxylpropyl)methacrylamide) as a novel mucoadhesive polymer for nasal drug delivery

Nasal drug administration is an attractive option for systemic drug delivery, but it is often limited by inadequate nasal drug absorption. In this study, we investigated novel mucoadhesive poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA)-based copolymers functionalised with maleimide moieties as formulations to enhance the retention of dosage forms on the nasal mucosa. PHPMA and its maleimide derivatives were synthesised using controlled radical polymerisation, resulting in polymers with well-defined structures, low dispersity, and variable maleimide functionality. Functionalisation of PHPMA with maleimide groups substantially improved its mucoadhesive properties. Importantly, copolymers with low maleimide content, which were nevertheless sufficient for mucoadhesion, showed no significant cytotoxicity against HEK293 cells and no mucosal irritation in a slug mucosal irritation assay. These PHPMA derivatives demonstrate excellent potential as mucoadhesive materials for developing dosage forms for nasal drug delivery.