Abstract 300: A Biodegradable Wrap for Peri-vascular Delivery of Pro-resolving Lipid Mediators
Introduction: Persistent inflammation following vascular injury leads to excessive scarring, limiting the success of vascular interventions. Recent work has identified that endogenous specialized proresolving lipid mediators (SPM) such as resolvin D1 (RvD1) actively orchestrate the process of resolution, exerting vasculo-protective effects without associated toxicity. We propose local vascular delivery of SPM through a biodegradable wrap.
Methods: RvD1 (200 ng) was heat-sealed between thin layers of polycaprolactone (PCL) or poly-lactic-co-glycolic acid (PLGA). PLGA membranes differed in their composition of lactic versus glycolic acid (%-lactide). Directional drug release was measured via EIA in a cell-free system in vitro and into rabbit aortas exposed to pulsatile flow ex vivo. Bioactivity was confirmed on human vascular smooth muscle cells (VSMC) using migration and proliferation assays.
Results: Of the constructs tested, a 3-layered PLGA wrap consisting of 85%/75%/50%-lactide provided the most favorable drug elution (Fig1a), with sustained release of >800 pg/day for at least 14 days and nearly all elution occurring from the 50%-lactide side (Fig1b). Perivascular application of this wrap ex vivo with the 50%-lactide side facing “in” demonstrated uptake into rabbit aortic walls at 8 hours (0.4 ± 0.1 pg/mg). VSMC cultures exposed to drug-loaded wraps showed inhibition of migration (40%) and proliferation (25%).
Conclusion: We demonstrate sustained and directional elution of therapeutically relevant amounts of biologically-active RvD1 through a biodegradable perivascular wrap, providing opportunity for translational studies of SPM in vascular injury.
Author Disclosures: B. Wu: None. K.D. Lance: None. A. Chatterjee: None. G. Mottola: None. M. Chen: None. S.R. Komshian: None. T.A. Desai: None. M.S. Conte: None.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.