Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 181, Issue -, Pages 218-226Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2022.11.015
Keywords
Targeted drug delivery; Antibody coating; Intravascular device; Endothelial colony-forming cells; Genetic engineering; H-2Kk; Human ?-CGRP
Categories
Funding
- Heart and Stroke Foundation of Canada
- [G-15-0009372]
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This study aimed to capture genetically engineered pig endothelial colony-forming cells (ECFCs) using ex vivo antibody-coated intravascular devices as a proof of concept for their potential for in vivo targeted drug delivery.
This study was designed to test the ability of ex vivo antibody-coated intravascular devices to capture genetically engineered pig endothelial colony-forming cells (ECFCs) as proof of concept for their potential for in vivo tar-geted drug delivery. Human alpha-calcitonin gene-related peptide (alpha-CGRP) was chosen as the therapeutic molecule as it is unsuitable for systemic administration due to its potent peripheral arterial vasodilatory effect and short half-life in blood, requiring local delivery to yield therapeutic benefit in a particular vascular bed. H-2Kk, a murine leukocyte surface antigen, served as the selection marker for genetically modified ECFCs. H-2Kk antibody was immobilized on electropolished cobalt-chromium (CC) discs, CC stents and ePTFE grafts through dopamine self-polymerization. The functionalized surface was integral and smooth, lacked or had significantly reduced chemical signals specific for substrates. Pig bone marrow-derived ECFCs transfected with a plasmid constructed for H-2Kk and alpha-CGRP expression produced H-2Kk on cell surface and biologically active alpha-CGRP in culture medium. H-2Kk antibody-coated substrates bound H-2Kk ECFCs but not control ECFCs in vitro. Bare or only dopamine-coated substrates did not bind H-2Kk ECFCs. These data suggest that implantation of antibody functionalized devices combined with injection of genetically modified ECFCs could be potentially applied for targeted drug delivery.
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