Local Delivery Of Tacrolimus Via Drug-eluting Sutures For Prevention Of Stenosis At The Vascular Anastomosis Site
Hidenori Hayashi1, Kunal S. Parikh2, Aditya Josyula2, Takahiro Inoue1, Takuma Fukunishi2, Huaitao Zhang2, Revaz Omiadze2, Richard Shi2, Youseph Yazdi2, Justin Hanes2, Laura M. Ensign2, Narutoshi Hibino1.
1Section of Cardiac & Thoracic Surgery, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, USA, 2Center for Nanomedicine at JHU, Baltimore, MD, USA.
Objective(s): The vascular anastomosis site is the most common location of neointimal hyperplasia. In highly reactive tissues, such as the pulmonary vein, neointimal hyperplasia results in vessel narrowing (stenosis). Local delivery of anti-proliferative drugs, such as tacrolimus, could prevent stenosis at the anastomosis site without systemic toxicity. Here, we developed tacrolimus-eluting, nanofiber-coated, non-absorbable sutures to prevent post-operative stenosis.
Methods: Tacrolimus-eluting nanofibers were created and coated around a non-absorbable nylon suture using a novel electrospinning technique. The 8-0 sutures were characterized for morphology, breaking strength, and in vitro drug release. The rat abdominal aorta was transected and sutured with drug-eluting and control nylon sutures to create vascular anastomosis model for histological analysis. Intraperitoneal injection of tacrolimus in conjunction with nylon sutures was also evaluated for efficacy and safety.
Results: Nanofiber-coated sutures met United States Pharmacopeia requirements for diameter and breaking strength for clinical use. The sutures provided tacrolimus release for up to 14 days in vitro. In the rat vascular anastomosis model, tacrolimus-eluting sutures showed significantly lower neointimal hyperplasia compared with the nylon control group while maintaining endothelialization. A toxic dose of systemically administered tacrolimus was required to achieve a similar level of neointimal hyperplasia inhibition provided by tacrolimus-eluting sutures.
Conclusions: Nanofiber-coated sutures provided safe and effective local delivery of tacrolimus to reduce neointimal hyperplasia at anastomosis site.
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