Development of maleimide-modified poly(N-(2-hydroxylpropyl)methacrylamide) as a novel mucoadhesive polymer for nasal drug delivery
Shan X. Pola R. Kaldybekov D.B. Aspinall S. Buang F. Williams A.C. Etrych T. Khutoryanskiy V.V.
17 September 2025Elsevier Ltd
European Polymer Journal
2025#237
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.
Maleimide , Mucoadhesion , Mucoadhesive materials , Nasal drug delivery , Poly(N-(2-hydroxylpropyl)methacrylamide)
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Reading School of Pharmacy, University of Reading, Whiteknights, PO Box 224, Reading, RG6 6DX, United Kingdom
Small Molecules CMC Drug Product, BeOne Ltd., 30 Science Park Road, Zhongguancun Life Science Park, Changping District, Beijing, 102206, China
Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovského nám. 2, Prague 6, Czech Republic
Department of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Department of Clinical, Pharmaceutical & Biological Sciences, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, United Kingdom
Centre for Drug Delivery Technology and Vaccine (CENTRIC), Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Malaysia
Physicochemical, Ex Vivo and Invertebrate Tests and Analysis Centre (PEVITAC), University of Reading, Whiteknights, PO Box 224, Reading, RG6 6DX, United Kingdom
Reading School of Pharmacy
Small Molecules CMC Drug Product
Institute of Macromolecular Chemistry of the Czech Academy of Sciences
Department of Chemistry and Chemical Technology
Department of Clinical
Centre for Drug Delivery Technology and Vaccine (CENTRIC)
Physicochemical
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