SELF-GELLING ELASTIN AND SILK-ELASTIN RECOMBINAMERS FOR TIMOLOL OPHTHALMIC ADMINISTRATION IN THE TRATAMIENT OF THE GLAUCOMA

PAULA GRISANZIO; ALLEMANDI DANIEL; ARIAS VALLEJO JAVIER; DANIELA A QUINTEROS; JOSE MARÍA BERMUDEZ; JOSÉ CARLOS RODRÍGUEZ-CABELLO, ; ALICIA FERNANDEZ COLINO; PALMA SANTIAGO

Mar del Plata

Congreso; XLVIII REUNION ANUAL DE LA ASOCIACION ARGENTINA DE FARMACOLOGIA EXPERIMENTAL; 2016

SAFE

INTRODUCTION:The development of topical ophthalmic formulations for the treatment of eye diseases such as glaucoma, present a challenge, since most drugs are hardly absorbed, having bioavailabilities from 1-10%. It is consequence of a rapid and extensive loss of the formulation from the pre-corneal area due to the turnover of the lacrimal drainage. An alternative to increase the residence time of formulations is the use of bioadhesive systems. Taking this into account, here we developed an elastin-like and a silk-elastin like recombinamers, named respectively as ELR and SELR, for their incorporation in an ophthalmic formulation against glaucoma. Our hypothesis is that due to the thermo-sensitive behavior of these materials, the formulation could be administered topically as drops, and once sensing the temperature of the eye, suffer a shift to a gel system, which could help to prolong the permanence of the formulation in the eye, and therefore, could enhance the therapeutic effect.METHODS:The termosensitive gels each system timolol (0.5% w / w) was charged and the release of timolol and erosion of ELR and SELR were evaluated for 8 hours. In vivo studies were performed on New Zealand rabbits. Each formulation was placed into the conjuntival fornix and the intraocular preassure (IOP), Irritation and Adhesion were measure. RESULTS:Both recombinamers display clearly differences on the release kinetics. It was determined using the model Korsmeyer, The results indicated the percent release at 8 hours was 80.39% and 40.04% of Timolol for ELR and SELR, respectively. In both cases the release mechanism timolol responded to an anomalous diffusion. The rate constant (k), incorporating structural and geometric characteristics of the system was higher for ELR indicating a faster rate of drug release. This behavior can be inferred that the same erosion / dissolution of the matrix predominates in drug release, which coincides with erosion studies indicate greater resistance and mechanical stability of the gels SELR. In vivo tests evidenced that formulations containing the recombinamers further decreased the IOP when compared with the control formulation (without any of the recombinamers). Furthermore, SELR-formulation was found to be more effective that its counterparts ELR-formulation, which agrees with the enhanced mechanical properties provided by the presence of the silk moieties. CONCLUSIONS:These results evidenced that the self-gelling ELR and SELR have great potential for its use as components of ophthalmic pharmaceutical formulations.Keywords: Timolol, SELR, ELR, gels termosensitive