“This mechanistic model empowers and reassures clinicians about the amount of active paclitaxel that our patients are exposed to, while offering insights and a framework for accelerating the preclinical development of new technologies such as those including sirolimus,” said Sahil A. Parikh, M.D., co-author and Director of Endovascular Services at the Columbia University College of Physicians and Surgeons.
LEXINGTON, Mass., Aug 15, 2019 — CBSET Inc., a not-for-profit preclinical research institute dedicated to biomedical research, education, and advancement of medical technologies, announced today that its scientists have published data and analyses (“Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics”) that provide critical insights into the interplay between target anatomy and device attributes in determining balloon and stent-based paclitaxel retention in healthy and diseased arteries.
These findings will transform our understanding of the safety and efficacy of paclitaxel-coated devices used in the treatment of peripheral artery disease (PAD) in hundreds of thousands of patients every year.
“The recent controversy regarding a possible increase in risk for mortality after treatment with paclitaxel-coated balloons and stents at 2 and 5 years post-treatment has raised concerns regarding the clinical paradigm for evaluating these devices, while also highlighting the lack of a fundamental understanding of how these devices deliver and retain drugs in the artery and at what concentrations,” said Dr. Sahil A. Parikh, M.D., co-author and Director of Endovascular Services at the Columbia University.
“Our past research has focused on these very issues, defining the roles of drug lipophilicity and size as well as lesion composition. What was lacking was a framework for integrating such experimental data and coupling it to models of coating dissolution. By doing just this, the current study provides novel insights into local drug retention and tissue dosing after treatment with drug-coated devices. Tissue retention dynamics are now understood as comprising three primary phases: luminal coating dissolution, tissue embedded coating dissolution, and receptor dissociation, with the latter determining the rate of terminal clearance. Receptor expression in healthy porcine tissue is similar for paclitaxel and sirolimus, but can be elevated by injury and disease. Moreover, simulations predict that tissue mineralization, which was previously identified as a hindrance to arterial drug distribution, can also hinder the dissociation of receptor-bound drug and provide a mechanism for multi-year drug retention,” said CBSET Director of Research and Innovation Dr. Rami Tzafriri, lead author of the published study.
“Mechanistic insight bridges the preclinical and clinical experiences and is ultimately the only effective means of resolving seeming conflicts or disparities in observations. The groundbreaking work reported herein builds upon a wealth of hands-on experience with these devices and over 20 years of NIH-funded fundamental research in endovascular drug delivery to provide the precision needed to produce a coherent paradigm by which to appreciate this complex field. As we move forward, it is incumbent upon us to continue to employ and develop these tools, to help industry and regulators develop safer and more efficacious therapies,” added Elazer R. Edelman, M.D., Ph.D., chairman and co-founder of CBSET, and senior author on the paper.
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CBSET Inc. — 500 Shire Way, Lexington, MA 02421 — is the preclinical research leader in critically important therapeutic fields such as interventional cardiology, renal disease and dialysis, chronic drug-resistant hypertension, women’s health, minimally invasive surgery, orthopedics, biological and synthetic tissue repair, drug delivery, bioresorbable devices, and combination medical device and drug-eluting products. Learn more about CBSET’s expert biomedical research services or please contact us.