Development of Maleimide-Modified Poly(N-(2-Hydroxylpropyl)Methacrylamide) as a Novel Mucoadhesive Polymer for Nasal Drug Delivery

Abstract

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 enriched 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.

Note:
Funding Information: The authors are grateful to the University of Reading and the China Scholarship Council (201707040071) for funding the PhD studentship of Xiaoning Shan. The authors are grateful to the Czech Science Foundation for funding (grant number 22-12483S) experiments on the synthesis and characterisation of these polymers. V.V.K. acknowledges the financial support provided by the Royal Society for his Industry Fellowship (IF/R2/222031).

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Keywords: poly(N-(2-hydroxylpropyl)methacrylamide), mucoadhesion, maleimide, mucoadhesive materials, nasal drug delivery