title: Preliminary characterization of dexamethasone-loaded cross-linked hyaluronic acid films for topical ocular therapy.
abstract: The aim of this work was to design and characterize cross-linked hyaluronic acid (HA)-itaconic acid (IT) films loaded with dexamethasone sodium phosphate salt (DEX) for topical therapy of inflammatory ocular surface diseases. Films were chemically cross-linked with polyethylene glycol diglycidyl ether (PEGDE), then physical and mechanical characterization by stress-strain, X-ray diffraction, X-ray fluorescence spectrometry and swelling assays was conducted. A sequential in vitro therapeutic efficacy model was designed to assess changes in interleukin (IL)-6 production in an inflamed human corneal epithelial (HCE) cell line after film exposure. Changes in cell proliferation after film exposure were assessed using the alamarBlue(®) proliferation assay. Experimental findings showed desirable mechanical properties and in vitro efficacy to reduce cell inflammation. A moderately decreased proliferation rate was induced in HCE cells by DEX-loaded films, compared to commercial DEX eye drops. These results suggest that DEX and HA have opposite effects. The sequential in vitro therapeutic efficacy model arises as an efficient tool to study drug release from delivery systems by indirect measurement of a biological response.
authors.affiliation: Institute of Applied Ophthalmo-Biology (IOBA), University of Valladolid, 47011 Valladolid, Spain; PLAPIQUI, CONICET, National University at Bahía Blanca (UNS), 8000 Bahía Blanca, Argentina; Department of Biology, Biochemistry and Pharmacy, UNS, 8000 Bahía Blanca, Argentina.
authors.forename: J A
authors.initials: JA
authors.lastname: Calles
authors.affiliation: Institute of Applied Ophthalmo-Biology (IOBA), University of Valladolid, 47011 Valladolid, Spain; Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: A
authors.initials: A
authors.lastname: López-García
authors.affiliation: PLAPIQUI, CONICET, National University at Bahía Blanca (UNS), 8000 Bahía Blanca, Argentina.
authors.forename: E M
authors.initials: EM
authors.lastname: Vallés
authors.affiliation: UNITEFA, CONICET, National University of Córdoba, X5000HUA Córdoba, Argentina.
authors.forename: S D
authors.initials: SD
authors.lastname: Palma
authors.affiliation: Institute of Applied Ophthalmo-Biology (IOBA), University of Valladolid, 47011 Valladolid, Spain; Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Electronic address: yol@ioba.med.uva.es.
authors.forename: Y
authors.initials: Y
authors.lastname: Diebold
mesh_terms: D000287:Administration, Topical; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003315:Cornea / Q000187:drug effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000737:chemistry*; D013386:Succinates / Q000737:chemistry
chemical_list: D009883:Ophthalmic Solutions; D013386:Succinates; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; D006820:Hyaluronic Acid; C005229:itaconic acid
keywords: Dexamethasone; Hyaluronan; Inflammation; Model; Ocular