Exploring mucoadhesive and toxicological characteristics following modification of linear polyethylenimine with various anhydrides

Fu, M., Moiseev, R. V. ORCID: https://orcid.org/0000-0002-4358-9981, Hyder, M., Hayes, W. ORCID: https://orcid.org/0000-0003-0047-2991, Amadesi, S., Williams, A. C. ORCID: https://orcid.org/0000-0003-3654-7916 and Khutoryanskiy, V. V. ORCID: https://orcid.org/0000-0002-7221-2630 (2024) Exploring mucoadhesive and toxicological characteristics following modification of linear polyethylenimine with various anhydrides. Biomacromolecules. ISSN 1526-4602 doi: 10.1021/acs.biomac.4c00220

Abstract/Summary

Linear polyethylenimine (L-PEI) has numerous applications, such as in pharmaceutical formulations, gene delivery, and water treatment. However, due to the presence of secondary amine groups, L-PEI shows a relatively high toxicity and low biocompatibility. Here, various organic anhydrides were used to modify L-PEI to reduce its toxicity and enhance its functionality. We selected methacrylic anhydride, crotonic anhydride, maleic anhydride, and succinic anhydride to modify L-PEI. The structure of the resulting derivatives was characterized using 1H NMR and FTIR spectroscopies, and their behavior in aqueous solutions was studied using turbidimetric and electrophoretic mobility measurements over a broad range of pHs. A fluorescence flow through method determined the mucoadhesive properties of the polymers to the bovine palpebral conjunctiva. Methacrylated L-PEI and crotonylated L-PEI showed strong mucoadhesive properties at pH 7.4, likely due to covalent bonding with mucin thiol groups. In contrast, maleylated and succinylated L-PEI were poorly mucoadhesive as the pH was above their isoelectric point, resulting in electrostatic repulsion between the polymers and mucin. The toxicity of these polymers was evaluated using in vivo assays with planaria and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay in human alveolar epithelial cells. Moreover, the irritancy of polymers was assessed using a slug mucosa irritation assay. The results demonstrated that anhydride modification mitigated the adverse toxicity effects seen for parent L-PEI.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/117496
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > NMR (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	American Chemical Society
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