AimDevelopment of mucoadhesive self-emulsifying drug delivery systems (SEDDS) providing a prolonged ocular residence time for poorly soluble active pharmaceutical ingredient. Methodsl-Cysteine was covalently linked to 6-mercaptonicotinamide. The obtained ligand, Cysteine-6-mercaptonicotinamide (Cys-6-MNA) was attached to Eudragit® L100-55 via a carbodiimide mediated amide bond formation. The resulting entirely S-protected thiolated Eudragit® L100-55 was characterized regarding the degree of modification as well as stability toward oxidation in the presence of strong oxidizing agent (H2O2). The S-protected thiolated Eudragit® L100-55 was incorporated into SEDDS via hydrophobic ion pairing with benzalkonium chloride (BAK) in a concentration of 2% (m/m). S-protected thiolated Eudragit® L100-55-BAK ion pair SEDDS (S-protected thiolated EU-BAK SEDDS) were characterized regarding their physicochemical and mucoadhesive properties. Econazole nitrate (EN) was incorporated into SEDDS in concentration of 1% (m/m) and in vitro drug release was assessed. Furthermore, toxicity study was performed on procine corneas via resazurin assay. ResultsThe entirely S-protected thiolated Eudragit® L100-55 exhibited 282 ± 78.25 µmol of MNA per gram of polymer. Ellman’s test confirmed no free thiol groups and stability study showed no significant increase in dynamic viscosity overtime. The droplet size of developed SEDDS in simulated lacrimal fluid was below 100 nm with polydispersity index below 0.3. S-protected thiolated EU-BAK SEDDS exhibited 2.5-fold higher mucoadhesive properties than blank SEDDS on ocular mucosa. S-protected thiolated EU-BAK SEDDS showed sustained EN release over period of 8 h and no pronounced corneal toxicity in 0.5% (m/v) concentration. ConclusionAccordingly, these mucoadhesive SEDDS can be considered as promising ocular delivery system for EN.