Resumen de Asociación de sistemas nanoestructurados con fluorometolona para el tratamiento de enfermedades inflamatorias
Roberto Carlos González Pizarro
In the therapeutic approach to ocular inflammatory diseases, both non-steroidal anti-inflammatory drugs and corticosteroids have been used in different dosage forms with the aim of restoring ocular homeostasis. In the treatment, those ocular inflammatory states that affect structures of the anterior segment are generally administered as eye drops dosage form, which present a limited pharmacological effect, due to the precorneal elimination routes such as tear turnover, which allows access to intraocular tissues of 5% of the instilled formulation. When the posterior segment of the eye is affected, invasive forms of administration, such as implants and intraocular injections, lead to discomfort for the patient and make adherence to treatment difficult. In particular, the use of corticoids in inflammations of the uvea (uveitis) caused by systemic diseases such as Lupus, show an increase in intraocular pressure as a side effect. However, Fluorometholone (FMT) is a moderately potent corticosteroid used to treat allergies and inflammations of the anterior segment of the eye without inducing appreciable changes in intraocular pressure (main adverse effects of these drugs). According to the above, the main objective of this work was the development and characterization of polymeric nanostructured systems containing FMT for the treatment of inflammatory conditions of the anterior and posterior segment of the eye. Three systems were developed with FMT: PLGA nanoparticles (NPs), in-situ forming gel with NPs and functionalized NPs with cell-penetrating peptides (TAT49-57, pAntp43-58 and G2). PLGA NPs, gel and functionalized NPs demonstrated physicochemical characteristics suitable for ocular administration. The PLGA NPs and the thermosensitive gel showed a biopharmaceutical profile of sustained release of FMT. The three developed systems presented an optimal ocular tolerance, demonstrated by in vitro (MTT and HET-CAM®) and in vivo (Draize) tests. Ocular anti-inflammatory efficacy trials showed that PLGA NPs and in-situ forming gel have a significantly greater effect in reducing inflammation than the commercial drug. On the other hand, the NPs functionalized with TAT49-57 and G2, exhibited a greater effect in the reduction of the expression of proinflammatory cytokines, evidencing, in addition, an internalization in vitro as in vivo greater than with the peptide pAntp43-58. In conclusion, according to the results obtained, the nanostructured systems with FMT developed could constitute a new strategy for the treatment of ocular inflammation. In particular, NPs would be useful in daytime treatment and thermosensitive gel in the maintenance of nocturnal therapy
