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Testing of an autogelling elastin like recombinamer for ophthalmic applications
Congreso; Engineering and Regenerative Medicine International Society EU Meeting; 2014
Testing of an autogelling elastin like recombinamer- for ophthalmic applications Alicia Fernández-Colino,1 Daniela Quinteros,2, Santiago de Palma,2 Daniel Allemandi,2 José C. Rodríguez-Cabello,2 Francisco J Arias,1. Corresponding: 1 BIOFORGE (Group for Advanced Materials and Nanobiotechnology) CIBER-BBN, University of Valladolid, Valladolid, Spain and 2 UNITEFA-CONICET, Faculty of Chemical Sciences, National Univ. of Córdoba, Córdoba, Argentina 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%. Among other factors, such low bioavailability 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 in the area of application is the use of bioadhesive systems. Taking this into account, we propose the incorporation of an autogelling elastin-like recombinarmer (ELR) 1 in the development of an ophthalmic formulation. Our hypothesis is that due to the thermo-sensitive behavior of this polymer, 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 facilitate the passage of the drug. Materials and Methods The ELR was obtained by molecular biology standar tecniques, with a complete control of the aminoacidic sequence. Franz cells were used for in vitro released studies. The drug-loaded hydrogel formed by the ELR was placed in the donor cell, while the receptor cell was filled with release medium. At predetermined times aliquots of the receptor cell were taken and meassured by UV absorbance. The experimental data were fitted to the kinetic model of Korsmeyer2. Relative to ex vivo permeation studies, the corneal tissue was extracted from New Zealand rabbits and placed between both compartments of the cell. The quantitative determination of the drug was performed by a reverse-phase HPLC. The potential ocular irritancy of the samples under test were evaluated using a slightly modified version of the Draize test. The adhesion behavior of the formulation was evaluated with a binocular indirect ophthalmoscope Results In vitro delivery profiles shows that the drug release is sustained over the period studied, with a visible absence of burst release at the initial time-points. The irritation tests reveal the safety of the formulation containing the ELR. The coefficient of permeability of the studied drug in polymer solution is lower than that displayed in control solution (without polymer). Such decreased can be attributed to a higher viscosity of the formulations containing the polymer, which mainly retards the diffusion of the drug until de corneal surface. Relative to the adhesion tests, they revealed enhanced bioadhesive properties when compared to the control. Discussion and Conclusions These results suggest that the autogelling ELR may have great potential for its use as a component of ophthalmic pharmaceutical formulations due to its proven safety and the provided increased in the viscosity of the system. Acknowledgements. MINECO Project PRI-PIBAR-2011-1403 References 1.Arias, F. J, Santos, M. Fernández-Colino, A., Pinedo, G., Girotti, A. Current Topics in Medicinal Chemistry, 14, (2014) 2.Rigo MV, Allemandi DA, Manzo RHDrug Deliv. 16(2):108-15 (2009) Disclosures Authors have nothing to disclose.