Two optimized pranoprofen-loaded poly-L-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF- 39 F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formu- 40 lations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly 41 prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone 42 (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile 43 of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranopro- 44 fen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and 45 analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations 46 with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for 47 ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sus- 48 tained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflamma- 49 tory efficacy studies suggest that the ocular application of the hydrogels containing azone was more 50 effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of 51 ocular irritancy have been detected for the produced hydrogels.