Abstract Body: Introduction
Current Drug-Coated Balloons (DCB) primarily deliver drugs in crystalline form, which can lead to distal embolization and inefficient vessel wall uptake due to luminal wash-off. DCB are also occlusive of perfusion. We evaluated a novel retrievable drug infusion stentgraft (RDIS), designed for continuous distal perfusion while delivering liquid Paclitaxel to an isolated segment of the iliac artery (Figure 1). We hypothesized that liquid phase delivery would result in superior transmural drug penetration.

Methods
Two Yorkshire pigs underwent fluorescent paclitaxel drug delivery to one iliac artery using RDIS followed by vessel explant at either 3 or 10 minutes (Figure 2). To quantify drug delivery by vessel layer, additional animals underwent Paclitaxel administration by DCB or our RDIS followed by vessel explant at 1 hour (n=2) and 24 hours (n=2). Laser capture dissection of histologic specimens was used to isolate 1) intima and adjacent cell layers 2) media, and 3) adventitia, using mass spectrometry (MS) to quantify the amount of Paclitaxel in ng/mm³ of tissue for these different delivery modalities. Separate animals underwent balloon injury with drug delivery by the RDIS (n=6) or DCB (n=5) followed by vessel extraction at one month. Lastly, animals underwent RDIS delivery of fluorescent sirolimus followed by vessel explant at 3 (n=3) and 8 minutes (n=3).

Results
Fluorescent microscopy showed liquid delivery of paclitaxel through the vessel by 10 minutes and sirolimus at 8 minutes. MS of tissue at 1 hour compared to 24 hours revealed an average concentration drop after DCB of 85% (3,323 vs 491 ng/mm³, respectively) within the intima. MS of the media showed an average 2.2-fold increase in paclitaxel concentration after RDIS as compared to DCB at 24 hours (2.6 vs 1.2 ng/mm³, respectively). Luminex analysis of tissue 1-month following treatment showed a decreased expression of pro-inflammatory IL-18 in vessels treated with the RDIS vs DCB (3,695 vs 10,506 ng/mL, respectively; p=0.003).

Conclusion
The RDIS platform overcomes the "wash-off" effect seen with crystalline DCB coatings by providing stable, liquid-phase delivery to the deeper vessel layers. By achieving superior medial drug concentration and significantly reducing long-term inflammatory markers (IL-18), the RDIS represents a promising advancement in the treatment of vascular restenosis while preserving perfusion during drug transfer and offers promise for new agents (sirolimus).