Synthesis and Evaluation of Methacrylated Poly(2-ethyl-2-oxazoline) as a Mucoadhesive Polymer for Nasal Drug Delivery
Xiaoning Shan, Sam Aspinall, Daulet B. Kaldybekov, Fhataheya Buang, Adrian C. Williams, Vitaliy V. Khutoryanskiy
Abstract
Methacrylated poly(2-ethyl-2-oxazoline) (PEOZ) was synthesized by partial hydrolysis of 500 kDa PEOZ, and the resulting poly[(2-ethyl-2-oxazoline)-co-ethylenimine] P(EOZ-co-EI) was subsequently reacted with methacrylic anhydride. The successful synthesis of methacrylated PEOZ (MAPEOZ) was confirmed by proton nuclear magnetic resonance (1H NMR), infrared spectroscopy, and differential scanning calorimetry. The degrees of hydrolysis and methacrylation were determined by 1H NMR spectra. MAPEOZ exhibited temperature-responsive properties, which were dependent on the degree of methacrylation. On that basis, three soluble MAPEOZ derivatives with different degrees of methacrylation were selected and investigated in cell toxicity studies, showing no significant cytotoxicity against the HEK293 cell line. A slug mucosal irritation assay showed that PEOZ and MAPEOZ do not cause mucosal irritation. The presence of methacryloyl groups and residual amines had a remarkable synergistic effect on the mucoadhesive properties of these polymers. These poly(2-ethyl-2-oxazoline) derivatives have excellent potential as mucoadhesive materials for developing formulations for drug delivery via mucosal routes of administration.