Nanospheres encapsulated everolimus delivery into arterial wall-the tissue pharmacokinetics and vascular response experimental study

Objective This study aimed to evaluate the pharmacokinetic profile and tissue effects of everolimus delivered into arterial wall using biodegradable nanospheres. Background Delivery of everolimus into the arterial wall is challenging due to its low-lipophilic profile. Methods A pharmacokinetic study included 28 porcine coronary arterial segments initially injured with balloon angioplasty followed by the local delivery of everolimus encapsulated in nanospheres (EEN) via injection through a microporous delivery catheter. The animals were sacrificed at 1 hour, 1,7,28, and 90-day follow-up. In the tissue effects study 16 coronary bare metal stent (BMS) were implanted following EEN delivery, 15 BMS following nanospheres delivery without the drug (reference group) and 16 implanted BMS served as a control. Angiographic and histology follow-up was scheduled at 28 and 90-day. Results The study showed high-everolimus concentrations in arterial tissue early after nanoparticles delivery followed by its gradual decrease to 1.15 +/- 0.40 ng/mg at 90 days. Histology analysis showed favorable biocompatibility and healing profile with comparable area stenosis between groups at both time-points. Conclusions The present study demonstrates for the first time the safety, biocompatibility, and long-term retention of everolimus in arterial tissue after single local delivery of biodegradable nanospheres.