TY - JOUR
T1 - Synthesis and Evaluation of Methacrylated Poly(2-ethyl-2-oxazoline) as a Mucoadhesive Polymer for Nasal Drug Delivery
AU - Shan, Xiaoning
AU - Aspinall, Sam
AU - Kaldybekov, Daulet B.
AU - Buang, Fhataheya
AU - Williams, Adrian C.
AU - Khutoryanskiy, Vitaliy V.
N1 - Funding Information:
The authors acknowledge the University of Reading and the China Scholarship Council (201707040071) for funding the Ph.D. studentship of X.S. The authors also thank the staff in the Chemical Analysis Facility (CAF, University of Reading) for assistance with thermal analysis. The authors thank Amnani Aminuddin for her technical help with cell culture experiments and the Faculty of Pharmacy UKM for providing the cell culture research facilities.
Publisher Copyright:
©
PY - 2021/11/12
Y1 - 2021/11/12
N2 - 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.
AB - 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.
KW - methacrylated polymers
KW - mucoadhesion
KW - mucoadhesive materials
KW - nasal drug delivery
KW - poly(2-ethyl-2-oxazoline)
UR - http://www.scopus.com/inward/record.url?scp=85119207293&partnerID=8YFLogxK
U2 - 10.1021/acsapm.1c01097
DO - 10.1021/acsapm.1c01097
M3 - Article
AN - SCOPUS:85119207293
SN - 2637-6105
VL - 3
SP - 5882
EP - 5892
JO - ACS Applied Polymer Materials
JF - ACS Applied Polymer Materials
IS - 11
ER -