In Vitro Corneal Compatibility of Cross-Linked Hyaluronan-Itaconic Acid Films

CALLES, JAVIER ADRIÁN; LOPEZ-GARCÍA, ANTONIO; PALMA, SANTIAGO DANIEL; VALLÉS, ENRIQUE MARCELO; DIEBOLD, YOLANDA

Viena

Simposio; International Symposium on Ocular Pharmacology and Therapeutics - ISOPT 2011; 2011

Paragon Convetions

The aim of this work was to evaluate the biocompatibility between ocular surface cells and crosslinked films of Hyaluronic Acid (HA)-Itaconic Acid (IT) films. We envision for these films potential applications as topical drug delivery system. Methods: HA-IT films were chemically modified using glutaraldehyde (GTA) and polyethylene glycol diglycidyl ether (PEGDE) as crosslinking agents. Swelling behavior of crosslinked hydrogels and pH changes were studied in culture medium. Structure and surface morphology were characterized by scanning electron microscopy (SEM). Suitable methods of sterilization were studied including UV exposure and immersion in 70% ethanol. A human corneal epithelial cell (HCE) line was used to determine the potential in vitro cell toxicity (XTT test) and cells proliferation (Alamar Blue test) after 24 hs exposure to films. Results: Swelling assays indicated that cross-linked systems were capable of maintaining their integrity in the aqueous medium during the experiments. All samples showed pores of different size by SEM. pH of the culture medium remained constant along the experiments. Sterilized PEGDE formulations exhibited in vitro viability over 80% while sterilized GTA cross-linked formulations lead into significant toxicity as expected. Corneal cells proliferation rate was maintained after 24 hs exposure on the different films with exception of those of HA that were used for control purposes. In this case proliferation was slightly increased. GTA films-exposed cells had a significant reduction in proliferation rate. Conclusions/Discussion: Studied formulations had good physicochemical properties to formulate drug delivery systems. The biocompatibility assays on PEGDE systems prove that they exhibit low toxicity and good HCE proliferation rates. Support CICYT MAT2010-20452-C03-01 (Spanish Ministry of Science and Technology), EADIC II-Erasmus Mundus Scholarship and UNS, CONICET and ANPCYT (Argentinean Research Agencies) UNS (Universidad Nacional del Sur, Argentina).