Betaine-modified hydroxyethyl cellulose (HEC): A biodegradable mucoadhesive polysaccharide exhibiting quaternary ammonium substructures

•Novel mucoadhesive betaine-modified HEC was successfully developed.•Betaine-modified HEC was synthesized via esterification of HEC.•Betaine-modified HEC displayed higher mucoadhesive properties compared to control.•The biodegradability of betaine-modified HEC provides benefit as a carrier. The aim of this study was to improve the mucoadhesive properties of hydroxyethyl cellulose (HEC) via the covalent attachment of betaine. Synthesis was carried out through esterification of HEC utilizing N-chlorobetainyl chloride. Betaine-modified HEC was characterized via FTIR and NMR analyses, ester quantification and zeta potential measurements. Enzymatic degradation and cell viability were also investigated. Moreover, rheological and mucoadhesive properties were evaluated. FTIR and NMR analyses confirmed the covalent attachment of betaine to HEC. Betaine-modified HEC contained 228.45±11.63 µmol/g ester bonds and its zeta potential was 0.37±0.19 mV. Enzymatic degradation studies showed the ability of lipase to cleave off betaine from HEC. Cytotoxicity studies demonstrated that betaine-modified HEC is up to a concentration of 0.3% not toxic. In comparison to unmodified HEC, betaine-modified HEC showed with mucus a 2.3- and 4-fold higher viscosity within 3 h and 6 h, respectively. Furthermore, betaine-modified HEC exhibited 23.5-fold higher mucoadhesive properties on porcine intestinal mucosa compared to unmodified HEC. In conclusion, betaine-modified HEC might be a useful biodegradable mucoadhesive polymer. [Display omitted]