3.2.6. In Vivo Pharmacokinetic Studies

Additionally, in vivo studies were carried out in a porcine model to assess the local and systemic pharmacokinetics of FTS-loaded rings. To ensure that rings were properly placed in the proximal part of the esophagus, initial studies were carried out using placebo rings (without FTS). We have shown successful endoscopic ring implantation into the proximal esophagus of one set of five pigs. After successful implantation of placebo rings, FTS-loaded rings were fabricated using pre-loaded PCl700-DMA resin formulation. Additionally, a post-fabrication UV curing was implemented to fabricate rings with mechanical properties appropriate for esophageal implantation. These FTS-loaded rings were deployed in the proximal esophagus of two sets of five pigs each for a period of 7 days. A daily endoscopy was performed to monitor the placement of rings. During endoscopic screening, it was observed that the rings were not present in the proximal esophagus of pigs

after day 1. This observation was corroborated by the absence of FTS in esophageal tissue and plasma collected at euthanasia at day 7 post ring administration. As the pigs were provided with an ad lib diet during the study, we hypothesize that the rings slipped into the pig's stomach along with the food. The PK analysis showed no accumulation of FTS in the esophageal tissue and no detectable plasma levels at day 7. These studies demonstrated that rings can be successfully inserted in the proximal part of the esophagus; however, further optimization in order to keep these rings in place for a longer time is needed.
