Delivery of Cell-Specific Aptamers to the Arterial Wall with an Occlusion Perfusion Catheter

Ofonime Udofot; Li-Hsien Lin; William H Thiel; Megan Erwin; Emily Turner; Francis J Miller Jr; Paloma H Giangrande; Saami K Yazdani

doi:10.1016/j.omtn.2019.03.005

Delivery of Cell-Specific Aptamers to the Arterial Wall with an Occlusion Perfusion Catheter

Mol Ther Nucleic Acids. 2019 Jun 7:16:360-366. doi: 10.1016/j.omtn.2019.03.005. Epub 2019 Mar 23.

Authors

Ofonime Udofot¹, Li-Hsien Lin², William H Thiel², Megan Erwin³, Emily Turner³, Francis J Miller Jr⁴, Paloma H Giangrande⁵, Saami K Yazdani⁶

Affiliations

¹ Internal Medicine, University of Iowa, Iowa City, IA, USA; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA, USA.
² Internal Medicine, University of Iowa, Iowa City, IA, USA.
³ Mechanical Engineering Department, University of South Alabama, Mobile, AL, USA.
⁴ Department of Medicine, Duke University, Durham, NC, USA; Pharmacology and Cancer Biology Program, Duke University, Durham, NC, USA; Department of Medicine, Veterans Administration Medical Center, Durham, NC, USA. Electronic address: francis.miller@duke.edu.
⁵ Internal Medicine, University of Iowa, Iowa City, IA, USA; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA, USA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA; Radiation Oncology, University of Iowa, Iowa City, IA, USA; Molecular & Cellular Biology Program, University of Iowa, Iowa City, IA, USA; Environmental Health Sciences Research Center (EHSRC), University of Iowa, Iowa City, IA, USA. Electronic address: paloma-giangrande@uiowa.edu.
⁶ Mechanical Engineering Department, University of South Alabama, Mobile, AL, USA. Electronic address: syazdani@southalabama.edu.

Abstract

Current strategies to prevent restenosis following endovascular treatment include the local delivery of anti-proliferative agents to inhibit vascular smooth muscle cell (VSMC) proliferation and migration. These agents, not specific to VSMCs, are deposited on the luminal surface and therefore target endothelial cells and delay vascular healing. Cell-targeted therapies, (e.g., RNA aptamers), can potentially overcome these safety concerns by specifically binding to VSMC and inhibiting proliferation and migration. The purpose of this study was to therefore demonstrate the ability of a perfusion catheter to deliver cell-specific RNA aptamer inhibitors directly to the vessel wall. RNA aptamers specific to VSMCs were developed using an in vitro cell-based systematic evolution of ligand by exponential enrichment selection process. Two aptamers (Apt01 and Apt14) were evaluated ex vivo using harvested pig arteries in a pulsatile flow bioreactor. Local drug delivery of the aptamers into the medial wall was accomplished using a novel perfusion catheter. We demonstrated the feasibility to deliver aptamer-based drugs directly to the medial layer of an artery using a perfusion catheter. Such cell-specific targeted therapeutic drugs provide a potentially safer and more effective treatment option for patients with vascular disease.

Keywords: Biodrug; aptamer; cell-targeted; ex vivo; local liquid delivery; neointima; perfusion catheter; pre-clinical.

Abstract

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