Eudragits: Versatile polymers for the preparation of physical-crosslinked hydrogels with mucus adhesion. From bench to animal model assays

DAVID ESPORRIN; MERCEDES FERNANDEZ; AYLA BASASORO; ANA SONZOGNI; ARANTXA ACERA; ITXASO CALAFEL; MARCELO CALDERON

Congreso; GEP-SLAP 2022; 2022

Hydrogels are three-dimensional networks, formed by several polymers, that can retain water inside themselves.[1] The component polymers are cross-linked between them by physical or chemical interactions. The benefit of cross-linking the chains with physical interactions allow us to avoid any chemical modification in their structure and work with already pharmaceutically approved polymers. This guarantees biocompatibility and reduces biological risk. Moreover, the polymeric chains are linked reversibly, wherein in the presence of an external stimulus (temperature, pH, mechanical forces), the hydrogel could be dissolved. During the last years, these materials have been used in presence of mucus layer for drug delivery in the eye[2], mouth[3], among others. The high degree of polymerization, high molecular weight, and flexible chains are some of the factors that will help in the interaction between the vehicle and the mucus. This interaction can prolong the residence time of the active drug in the application place. For example, a hydrogel with good eye-mucoadhesion behaviour will let an encapsulated drug to be released into the eye during a certain time. In the current study, we have investigated the influence that different Eudragits[4], a widely used polymer in pharmacy, have on the formulation of such hydrogels and their potential adhesion to the mucus present in the eye (Figure 1). Our final goal is to determine the structure-activity relationship in terms of hydrogel formulation, matrix stability, protein encapsulation, and release profiles. We have optimized a methodology to quantify the adhesion work between the hydrogel and the conjunctiva using a rheometer. Additionally, we will introduce some pre-clinic studies, using rabbits as an animal model, to demonstrate the eye-mucus adhesion of our materials and their potential benefits as ocular smart carriers, achieving with them an improvement on the actual surgical treatments. Nowadays, when an eye is seriously damaged, it is necessary to undergo surgery and transplant an amniotic membrane (AM) around it[5]. The AM contains several growth factors (GF) that help in eye recovery. We have extracted such GF and encapsulated them into our hydrogels. These novel systems will reduce the cost of the therapy and will increase patient compliance.