Introduction - Following a bypass graft surgery, almost half of the patients are prone to develop stenosis (thickening of the grafted vessel wall) within five years after the procedure. Perivascular delivery of active compounds is an appealing approach to prevent vein graft failure. We developed a single administration formulation to be applied during the surgical procedure on the grafted vessel. The presence of the formulation as well as a sustained release of the drug should be maintained for four weeks Methods - In this work, we developed a single administration drug delivery system, to be applied locally during the surgical procedure, around the vessel at the anastomosis site. Atorvastatin (ATV) was loaded in poly(lactic-co-glycolic acid) microparticles to achieve a sustained release kinetics of the drug, that would correlate with the time course of the development of the pathology (4 weeks). The microparticles were then incorporated into a hydrogel (cross-linked hyaluronic acid) to ensure residence at the site of injury and prolonged in situ delivery of ATV. The cross-linked hyaluronic acid hydrogel was received sterile. For the rodent model, PLGA microparticles were aseptically incorporated into the gel under laminar flow. For the pig model, prior microparticles sterilization using e-beam radiation or gamma rays was performed. Dose extrapolation was performed using interspecies allometric approaches. The formulation was tested on two animal models of intimal hyperplasia: a rodent carotid artery ligature model and a pig model of venous patch on carotid artery placement. Results - The challenges of the translation of a perivascular, implantable, drug delivery system between two animal models, were addressed: (i) drug release kinetics change due to additional sterilization, (ii) allometric dose extrapolation, (iii) viscosity change due to microparticle content increase to comply with dose scaling. In the rodent model the presence of the formulation showed a 63 % reduction in intimal hyperplasia compared to control (Figure1). These results were not reproduced in the porcine model, despite that a three-fold increase in angiogenesis demonstrated the action of ATV on site.Such discrepancy might be attributed to failure of allometric dose scaling in the context of local delivery. Indeed, the allometric dose scaling indicated that if 2 mg of ATV were administered per mouse, 10 mg should be administered per pig. Model differences in terms of implant degradation or metabolization need to be investigated. Additionally, the duration of the drug release decreased by 30% upon sterilization and this might not be optimal for the triggered pathology. Finally, viscosity increase of the implanted device is not optimal for a homogenous application of the formulation Conclusion - Perivascular administration is an appealing approach for the prevention of vein graft failure. Intra-species translation of efficient perivascular formulation remains an important challenge. Despite the encouraging results with an ATV-loaded microparticle/gel formulation applied on a mouse model, the results were still not reproduced on pigs. As a perspective, a dose increase is envisioned, to assess the efficacy of the formulation.