Development of a dual delivery of levofloxacin and prednisolone acetate via PLGA nanoparticles/ thermosensitive chitosan-based hydrogel for postoperative management: An in-vitro and ex-vivo study

Post-operative endophthalmitis (POE) is one of the most dreadful complications after intraocular surgery. For cata-ract surgery patients, both commercially available topical 0.5% levofloxacin and 1% prednisolone acetate (PA) oph-thalmic solution require at least 3 to 4 times application daily. In this study, we develop a dual drug delivery system composed of the thermosensitive chitosan/gelatin-based hydrogel containing PA and levofloxacin-loaded nanopar-ticles (LNPs). LNPs with negative surface charge show the monodisperse (polydispersity index-0.045), nanosize (-154.7 nm) and sphere-like structure. The optimal concentration of LNPs and PA to corneal epithelial cells was 5 mu g/mL and 50 mu g/mL, respectively. The developed dual drug delivery system (PAgel-LNPs) could gel at 34 degrees C within 63 s. The osmolarity of PAgel-LNPs was 301.2 +/- 1.5 mOsm/L. PAgel-LNPs showed a sustained-release profle for 7 days. Post-treatment of PAgel-LNPs in TNF-alpha-damaged corneal epithelial cells could decrease the inflammation (inflammatory genes (TNF-alpha, IL-6, MMP-3 andMMP-9) and IL-6 production) and cell death. In ex-vivo rabbit model of S. aureus keratitis, the anti-inflammation and anti-bacterial property have been demonstrated. These re-sults suggest that thermosensitive PAgel-LNPs may have the potential to use for the prevention of POE. (c) 2021 Elsevier B.V. All rights reserved.