Sistema gelificante in-situ contendo ácido hialurônico e indometacina para o tratamento de lesão química na córnea: desenvolvimento, caracterização e avaliação de eficácia.

Abstract

Corneal chemical injuries, if not treated appropriately, can result in visual impairment. The therapy consists in reducing local inflammation and promoting corneal re epithelialization. However, due to the structure and function of the human eye, it has a poor bioavailability. In-situ gelling systems are polymer-based formulations which undergo gelation through external stimulus, increasing retention and local concentration. This work’s aim was to create an in-situ gelling system made up of a poloxamer (K407), a thermosensitive polymer, containing hyaluronic acid (HA) and indomethacin (IND). The maximum concentration of IND in the system was initially determined using a fractional factorial design. For 12 suggested formulations, preliminary dynamic light scattering (DLS) and tube inversion tests were performed, showing values appropriate for ocular administration. Through rheological analysis the ideal formulation (F6) was identified, gelling at 34,2 ºC. The developed formulation had compatible maximum viscosity, superior to a commercial eye-drops, and a non-Newtonian rheological behavior. Polarized-light microscopy and cryogenic electron microscopy (Cryo-TEM) identified rounded micelles and a complex polymer network once heated. None incompatibilities were found among formulation’s components using infrared spectrum (FTIR). The developed formulation had released 52% of its content during 24 hours, moreover, eye penetration test revealed a satisfactory retention in tested corneas. In the biocompatibility test (HET-CAM) no irritancy was found. Significant reduction was identified in eye’s opacity scores in the 3º day, furthermore, relevant corneal thickness reduction was found in the 5º day through ocular coherence tomography (OCT). Histological examinations show that the animals given F6 had a more preserved corneal structure. As a result, the developed formulation might be a potential therapy alternative for alkaline chemical injury.