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

CALLES JAVIER; LOPEZ GARCIA; PALMA SANTIAGO; VALLES ENRIQUE; DIEBOLD YOLANDA

Viena

Simposio; The International Symposium on Ocular Pharmacology and Therapeutics; 2011

ISOPT

Background: The aim of this work was to evaluate the biocompatibility between ocular surface cells and cross-linked Hyaluronic Acid (HA)-Itaconic Acid (IT) films. Methods: HA-IT films were chemically modified using glutaraldehyde (GTA) and polyethylene glycol diglycidyl ether (PEGDE) as crosslinking agents. Swelling behavior of cross-linked hydrogels and pH changes were studied in culture medium. Structure and surface morphology were characterized by scanning electron microscopy (SEM). Suitability of sterilization methods was 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 cell proliferation rate alterations (Alamar Blue test) after exposure to films for 24h. Results: Swelling assays indicated that cross-linked systems were capable of maintaining their integrity in the aqueous medium during the length of experiments. All samples showed pores of different size by SEM. Culture medium pH remained constant throughout the experiments. Sterilized PEGDE-exposed cells exhibited viability superior to 95% while sterilized GTA cross-linked formulations lead into significant toxicity, as expected. Morphological details of PEGDE-exposed cells remained intact. HCE cells proliferation rate was maintained after exposure to the different films for 24h with exception of HA control ones, with which proliferation was slightly increased. GTA films-exposed cells showed a significant reduction in proliferation. Conclusions/Discussion: Studied formulations had good physicochemical properties to obtain drug delivery films. The biocompatibility assays showed no toxic effect and good HCE proliferation rates for PEGDE systems. These systems may be used as topical drug delivery platforms. Support: CICYT MAT2010-20452-C03-01 (Spanish Ministry of Science and Tec