**4. Discussion**

Development of new and innovative esophageal medication delivery systems are urgently needed for the treatment of EoE. In this study, we provide a comprehensive overview of the development of two types of drug delivery systems: (1) an FTS-eluting string for a rapid but sustained overnight release, and (2) a 3D-printed FTS-eluting ring to allow a long-acting constant drug release. In vitro release studies of FTS from drug-coated strings achieved the target drug release for a 24 h time period. FTS-eluting 3D-printed rings are capable of providing drug release for a period of 1 month or longer in vitro. FTS can be incorporated into the rings via two drug loading processes. Pre-loading involves addition of FTS into the resin formulation prior to ring fabrication. FTS loaded in these resin formulations was stable under accelerated stability storage conditions over six months, and FTS retained its physical and chemical properties. Our results have suggested that this method of drug loading exhibited controlled and sustained release of FTS over a period of 1 month (Figure 1). Alternatively, FTS can be incorporated into rings via postloading, i.e., after the 3D printing fabrication process. Results demonstrated post-loading of FTS after ring fabrication led to increase in burst release compared to rings loaded with FTS using the pre-loading process. Additionally, post-loaded rings showed faster zero-order release kinetics over 30 days in comparison to pre-loaded rings (Figure 3). Drug release kinetics can also be controlled by changing the composition and crosslink density of resin formulations. Our results showed that addition of a hydrophilic diluent (HEMA) to hydrophobic resin formulation PCL700-DMA lead to slower zero-order kinetics of FTS at 207 µg/day over 30 days compared to 282 µg/day obtained with FTS rings fabricated without HEMA (Figure 1). Mechanical properties of 3D printed rings can be optimized without impacting drug release kinetics of FTS. A post-fabrication UV-curing led to significant improvement in the mechanical properties of FTS loaded rings and higher FTS release rate in vitro compared to non-UV-cured rings. Collectively, these results demonstrate the flexibility of two fluticasone releasing platform technologies to achieve a controlled release kinetics and drug concentrations that can be translated to human use for treatment of EoE.
