QUINTEROS Daniela Alejandra
congresos y reuniones científicas
Self-gelling elastin and silk-elastin recombinamers for ophthalmic applications
ALICIA FERNANDEZ COLINO; DANIELA A QUINTEROS; JOSE M. BERMUDEZ; SANTIAGO D. PALMA; JOSÉ C. RODRÍGUEZ-CABELLO; ARIAS VALLEJO JAVIER
Congreso; congreso 27th European Conference on Biomaterials ESB2015 de la European Society for Biomaterials; 2015
INTRODUCTIONThe development of topical ophthalmic formulations for the treatment of eye diseases such as glaucoma, present a challenge1, 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, here we developed an elastin-like and a silk-elastin like recombinamers2,3, 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.EXPERIMENTAL METHODSThe recombinamers were obtained by molecular biology standard techniques. Rheological tests were performed to assess the thermogelling properties of both systems. Circular dichroism (CD) and FTIR analysis were carried out evaluate conformational changes on the differences in the rheological behavior. In vivo studies were performed on New Zealand rabbits. Each formulation was placed into the conjuntival fornix and the intraocular preassure (IOP) was measure by a Tonovet tonometer. RESULTS AND DISCUSSIONBoth recombinamers display clearly differences on the rheological properties. Concretely, the SELR show a dual physical gelation process, as consequence of the presence of the silk domains intercalated with amphiphilic engineering elastin-blocks, whereas the ELR displays a single gelation step. Such differences in the reological behavior were consequence of different conformational features of both materials, as verified by CD and FTIR. Relative to their pharmacological application, it should be pointed that the self-assembly nature of both recombinamers allowed facile encapsulation of the therapeutics within the gel. 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. CONCLUSIONSThese results evidenced that the self-gelling ELR and SELR have great potential for its use as components of ophthalmic pharmaceutical formulations.The initial liquid-like state of the recombinamers allows easy topical administration with ulterior gelification as consequence of the thermosensitive properties. In vivo studies show an enhanced reduction in IOP provided by the presence of the recombinamer, which was more accentuated in the case of SELR. Finally, the crosslinking mechanism based on self-assembly makes its preparation biologically friendly and very simple. REFERENCES1. Knight O J et al., Curr Opin Ophthalmol. 25(2):112-7.20142. Arias F. J, et al., A. Current Topics in Medicinal Chemistry, 14, 20143. Fernández-Colino A, et al., Biomacromolecules. 13;15(10):3781-93, 2014ACKNOWLEDGMENTSThe authors would like to thank MINECO Project PRI-PIBAR-2011-1403, and European Social Founding, Opertive Programme of ?Castilla y Leon? and JCyL, through ?Consejería de Educación for providing financial support to this project.