Advanced Self-gelling Devices Based on Elastin like Polymers for Ophthalmic Drug Delivery

ALICIA FERNANDEZ COLINO; DANIELA A QUINTEROS; JOSÉ MARÍA BERMUDEZ; SANTIAGO D. PALMA; ALESSANDRA GIROTTI; EDUARDO PÉREZ DEL RIO; FRANCISCO JAVIER ARIAS

Cancun

Congreso; XV Simposio Latinoamericano de Polímeros. XIII Congreso Iberoamericano de Polímeros; 2016

SLAP

The development of topical ophthalmic formulations for thetreatment of eye diseases such as glaucoma, present a challenge,since most drugs are hardly absorbed, having bioavailabilities from1-10%. Among other factors, such low bioavailability isconsequence of a rapid and extensive loss of the formulation fromthe pre-corneal area due to the turnover of the lacrimal drainage.An alternative to increase the residence time of formulations in thearea of application is the use of gel-based bioadhesive devices1.Taking this into account, here we developed an elastin-like and asilk-elastin like recombinamers2,3, named respectively as ELR andSELR, for their incorporation in an ophthalmic formulation againstglaucoma. Our hypothesis is that due to the thermo-sensitivebehavior of these materials, the formulation could be administeredtopically and once sensing the temperature of the eye, suffer a shiftto a gel system, which could help to prolong the permanence of theformulation in the eye, improve the bioavailability and therefore,could enhance the therapeutic effect.Experimental PartThe biopolymers were obtained by molecular biology standardtechniques. Rheological tests were performed to assess thethermogelling properties of both systems. AFM, Circular dichroism(CD) and FTIR analysis were carried out evaluate conformationalchanges. In vitro cytocompatibility was tested in ocular cell lines. Invivo studies were performed on New Zealand rabbits. Eachformulation was placed into the conjuntival fornix and theintraocular preassure (IOP) was measure by a Tonovet tonometer.Results and DiscussionsBoth recombinamers display clearly differences on the rheologicalproperties (Fig.1,Tab.1). Concretely, the SELR show a dualphysical gelation process, as consequence of the presence of thesilk domains intercalated with amphiphilic engineering elastinblocks,whereas the ELR displays a single gelation step. Suchdifferences in the rheological behavior were consequence ofdifferent conformational features of both materials, as verified byCD and FTIR. Relative to their pharmacological application, itshould be pointed that the self-assembly nature of bothrecombinamers allowed facile encapsulation of the therapeuticswithin the gel. In vivo tests evidenced that formulations containingthe recombinamers further decreased the IOP when compared withthe control formulation (without any of the recombinamers).Furthermore, SELR-formulation was found to be more effective thatits counterparts ELR, which agrees with the enhanced mechanicalproperties provided by the presence of the silk moieties.ConclusionsThese results evidenced that the self-gelling ELR and SELR havegreat potential for its use as components of ophthalmicpharmaceutical formulations. The initial liquid-like state of therecombinamers allows easy topical administration with ulteriorgelification as consequence of the thermosensitive properties. Invivo studies show an enhanced reduction in IOP provided by thepresence of the recombinamer, which was more accentuated in thecase of SELR. Finally, the crosslinking mechanism based on selfassemblymakes its preparation simple and biologically friendly.Acknowledgment: The authors would like to thank MINECOProjects PRI-PIBAR-2011-1403, and MAT2013-41723-R,European Social Founding and JCyL, for financial support.