Limitations of topical ocular application lead to unsufficient treatment in severe ocular disorders, therefore the researchers focused on novel drug delivery systems for the achievement of enhanced ocular bioavailability. Considering negatively charged corneal surface, self-cationic, mucoadhesive drug delivery systems gained more concern due to the enhanced penetration rates with the help of extended corneal contact time. In this study voricazole incorporated Eudragit (R) RS 100 (ERS) nanoparticles were prepared by spray-drying method. Physicochemical characteristic properties of the particles were evaluated. For the determination of antimicrobial activities of the formulations prepared, Microbroth Dilution Method and Adenosine Triphosphate (ATP) Bioluminescence Assay were used. For the determination of the duration time on the corneal surface, in vivo studies were conducted on sheeps using Schirmer Tear Test Method. The results revealed that enhanced ocular bioavailability can be achieved by ERS nanoparticles due to the enhanced residence time on the ocular surface up to 24 h.