title: Novel bioadhesive hyaluronan-itaconic acid crosslinked films for ocular therapy.
abstract: New hyaluronic acid (HA)-itaconic acid (IT) films have been previously synthesized and used as potential topical drug delivery systems (DDS) for ocular administration. In this study we explored homogeneous and heterogeneous crosslinking reactions of HA using glutaraldehyde (GTA) and polyethylene glycol diglycidyl ether (PEGDE) in the presence of IT, a naturally occurring compound that is non-toxic and readily biodegradable. We have studied the morphology, mechanical properties and in vitro biocompatibility between these new materials and ocular surface cells (human corneal epithelial cell line) and evaluated the biopharmaceutical performance of the designed formulations. Although all the synthesized materials exhibited good mechanical properties, the PEGDE modified films exhibited the best biocompatibility, with in vivo assays showing good adhesive performance and minimal irritation. PEGDE films were also tested for their effects in the treatment of intraocular pressure (IOP) in rabbits using timolol maleate (TM) as the model drug. These results may be useful for further design of novel bioadhesive matrix containing drugs by topical application in ophthalmology.
authors.affiliation: PLAPIQUI-CONICET, Universidad Nacional del Sur (UNS), Camino La Carrindanga km 7, Bahía Blanca, 8000, Argentina. javieradcalles@gmail.com
authors.forename: J A
authors.initials: JA
authors.lastname: Calles
authors.forename: L I
authors.initials: LI
authors.lastname: Tártara
authors.forename: A
authors.initials: A
authors.lastname: Lopez-García
authors.forename: Y
authors.initials: Y
authors.lastname: Diebold
authors.forename: S D
authors.initials: SD
authors.lastname: Palma
authors.forename: E M
authors.initials: EM
authors.lastname: Vallés
mesh_terms: D000268:Adhesiveness; D060433:Administration, Ophthalmic; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004853:Epoxy Resins / Q000737:chemistry*; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007429:Intraocular Pressure / Q000187:drug effects; D011817:Rabbits; D013386:Succinates / Q000737:chemistry*; D013999:Timolol / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D004853:Epoxy Resins; D013386:Succinates; C035364:Quetol 651; D013999:Timolol; D006820:Hyaluronic Acid; C005229:itaconic acid; D005976:Glutaral
keywords: BKC; Bioadhesive; DDS; Drug delivery; ESEM; FBS; GTA; Glaucoma; HA; HCE; Hyaluronan; IOP; IT; PEG; PEGDE; Polymer; RT; SR; TM; benzalkonium chloride; delivery systems; environmental scanning electron microscopy; fetal bovine serum; glutaraldehyde; human corneal epithelial; hyaluronic acid; intraocular pressure; itaconic acid; polyethylene glycol; polyethylene glycol diglycidyl ether; room temperature; swelling ratio; timolol maleate