%0 Journal Article %A Karthik Yadav Janga %A Akshaya Tatke %A Narendar Dudhipala %A Sai Prachetan Balguri %A Mohamed Moustafa Ibrahim %A Doaa Nabih Maria %A Monica M Jablonski %A Soumyajit Majumdar %T Gellan gum based sol-to-gel transforming system of natamycin transfersomes improves topical ocular delivery %D 2019 %R 10.1124/jpet.119.256446 %J Journal of Pharmacology and Experimental Therapeutics %P jpet.119.256446 %X Short precorneal residence time and poor transocular membrane permeability are the major challenges associated with topical ocular drug delivery. In the present research, the efficiency of electrolyte triggered sol-to-gel forming system of natamycin (NT) transfersomes were investigated for enhanced and prolonged ophthalmic delivery. Transfersomes were optimized by varying the molar ratios of phospholipid, Span and tocopheryl polyethylene glycol succinate (TPGS). NT transfersome formulations (FN) prepared with a 1:1 molar ratio of phospholipid-to-Span and low levels of TPGS showed optimal morphometric properties and were, thus, selected to fabricate the in situ gelling system. Gellan gum (0.3 %w/v) based FN loaded formulations (FNG) immediately formed an in situ gel in the simulated tear fluid, with considerable viscoelastic characteristics. In vitro cytotoxicity, in corneal epithelial cells, and corneal histology studies demonstrated the ocular safety and cytocompatibility of these optimized formulations. Transcorneal permeability of NT from these formulations were significantly higher than the control suspension. Moreover, the ocular disposition studies of NT, from the FN and FNG formulations, in the New Zealand male albino rabbits demonstrated the superiority of the electrolyte sensitive FNG formulations in terms of NT delivery to the ocular tissues. %U https://jpet.aspetjournals.org/content/jpet/early/2019/03/14/jpet.119.256446.full.pdf