“These preclinical studies transform our understanding of how drug coated balloons deliver drug to the artery and why there is no class effect, while also providing tools for understanding the role of tissue stiffening with disease. The combination of mechanistic insight with predictive modeling can help accelerate development of new technologies such as those including sirolimus analogs,” said Sahil A. Parikh, M.D., Director of Endovascular Services at the Columbia University College of Physicians and Surgeons.
LEXINGTON, MA — September 30, 2020 — CBSET Inc., a not-for-profit translational research institute, announced today that its potentially seminal preclinical study, “Balloon-based drug coating delivery to the artery wall is dictated by coating micro-morphology and angioplasty pressure gradients,” has been published in the Journal of Biomaterials.
“Concerns about paclitaxel toxicity have created an urgent opportunity for novel device design. CBSET has spent years of investment in the development of novel preclinical methods that enable the study of drug uptake from DCBs. This trailblazing study represents the culmination of our efforts and offers particular insights and a framework for accelerating the future development of innovative technologies,” said co-author Peter M. Markham, President and CEO, CBSET.
“Despite the availability of 5-year clinical studies on drug coated balloons (DCB), not much was known on how and where these devices deliver their drug load. Unlike stents that deliver drug at predictable strut locations with predictable elution kinetics, DCBs deliver solid drug microparticles and the mechanisms governing this were not well understood,” added Rami Tzafriri, Ph.D., lead author and Director of Research and Innovation for CBSET. “To address these needs, we developed an imaging method to visualize and quantify the endoluminal distribution and micromorphology of DCB coatings and to assess their tissue embedding. Moreover, we developed a novel computational model for predicting local arterial tissue microindentation pressures exerted by coating particles during balloon expansion, allowing for correlation of imaged coating transfer gradients across the treatment zone with simulated contact pressure gradients for each of the coating morphologies. Whereas imaging demonstrated differential endoluminal distribution of flaky and microcrystalline coatings, computational modeling related these differences to the ability of the microcrystals to amplify the angioplasty pressure at the treatment site.”
“Innovations in device design and preclinical models go hand-in-hand, as one enables the other. The methods that served the industry well in developing drug eluting stents are no longer adequate when evaluating devices that deliver coating rather than elute drug, creating a need for the introduction of new methods and concepts. The coupling of novel quantitative imaging after in vivo treatments and computational modeling of the micromechanical coating/tissue interactions is an important step toward filling this void,” said Elazer Edelman, M.D., Ph.D., Chairman and co-founder of CBSET, and senior author of the paper. “We can now begin to differentiate drug coated balloons based not simply on drug payload, excipient or dissolution rate, but also on net tissue spatial delivery. In doing so, it is possible not only to accelerate preclinical development but also to anticipate disease effects as part of that process.”
CBSET is a state-of-the-art biomedical research institute located in Lexington, Mass. As a not-for-profit entity, our mission is to advance biomedical research through innovative, high-quality preclinical services to achieve the scientific, regulatory and commercial goals of our sponsors. Our 40,000-foot, GLP-compliant, OLAW-assured, AAALAC-accredited facility includes vivaria, procedure rooms, catheterization / imaging labs, surgical and necropsy suites, histopathology, SEM, and a range of other technologies. We provide top-tier research with operational expertise by combining in vivo studies, in vitro studies, computational and 3D modeling, and complex histopathology into one integrated paradigm. Since inception, CBSET continues to develop technical and scientific acumen through collaborative projects in the medical device, pharmaceutical and academic communities. Learn more about CBSET’s expert biomedical research services.