Non-ionic hydroxyethylcellulose (HEC) has limited mucoadhesive properties for application in transmucosal drug delivery. In this study, HEC was chemically modified by reaction with glycidyl methacrylate. This allowed introducing the methacryloyl groups to HEC structure to make it capable of forming covalent bonds with the sulfhydryl groups present in the mucin glycoprotein to achieve enhanced mucoadhesive properties. The results showed a successful modification of HEC as confirmed by 1H NMR and FTIR spectroscopies. The quantification of methacryloyl moieties was conducted using HPLC. The toxicity studies using in vivo planaria acute toxicity assay, in vivo planaria fluorescent test, and in vitro MTT assay with Caco-2 cell line confirmed that the chemical modification of HEC does not result in any toxicological effects. Mucoadhesive wafers were developed based on parent and modified HEC as a model dosage form for buccal delivery. The mucoadhesive properties of modified HEC assessed using a tensile test were found to be significantly better compared to unmodified HEC.
Hydroxyethylcellulose (HEC) is a non-ionic water-soluble polymer with poor mucoadhesive properties. The mucoadhesive properties of hydroxyethylcellulose can be improved by modifying it through conjugation with molecules containing maleimide groups. Maleimide groups interact with the thiol groups present in cysteine domains in the mucin via Michael addition reaction under physiological conditions to form a strong mucoadhesive bond. This will prolong the residence time of a dosage form containing this modified polymer and drug on mucosal surfaces. In this study HEC was modified by reaction with 4-bromophenyl maleimide in varying molar ratios and the successful synthesis was confirmed using 1H NMR and FTIR spectroscopies. The safety of the newly synthesised polymer derivatives was assessed with in vivo planaria assays and in vitro MTT assay utilising Caco-2 cell line. The synthesized maleimide-functionalised HEC solutions were sprayed onto blank tablets to develop a model dosage form. The physical properties and mucoadhesive behavior of these tablets were evaluated using a tensile test with sheep buccal mucosa. The maleimide-functionalised HEC exhibited superior mucoadhesive properties compared to unmodified HEC.