Study Evaluates Optimizing Endovascular Drug Delivery Using Stents With a Deployable Coating

February 28, 2018—CBSET, a not-for-profit preclinical research institute, recently announced that its scientists have published data and analyses that provide insights into the tissue distribution patterns of antiproliferative drugs released from stents for treatment of coronary artery disease, which may have application to endovascular drug delivery therapies for coronary and peripheral lesions.

The study, "Defining drug and target protein distributions after stent-based drug release: durable versus deployable coatings," by Abraham Rami Tzafriri, PhD, et al is available online in Journal of Controlled Release (2018;274:102–108).

Dr. Tzafriri, who is the institute's Director of Research and Innovation, explained the study in the CBSET announcement. He stated, "The frustration is that stent designs that release similar drugs from a conformal coating are increasingly difficult to differentiate using tissue growth metrics in animal models or clinical metrics in human. It is only through reassessment of the role of each design parameter that we can hope to achieve disruptive innovation. To support such innovations, we developed an immunofluorescent method that simultaneously tracks the distribution of drug and its intracellular binding proteins within stented arteries. Using these methods we demonstrated that deployment of drug microcrystals using an absorbable coating resulted in spatially and temporally more uniform drug delivery compared to traditional durable coated stents."

Also in the press release, the study's Senior Investigator Elazer Edelman, MD, who is also Chairman and Cofounder of CBSET, commented, "Innovations in devices design and preclinical models go hand-in-hand, as one enables the other. Early development in bare and drug-eluting stents have taught us much about vascular biology, yet further innovation in stent design has been hampered by preclinical models that could not determine much more than bulk tissue content and are limited in their ability to distinguish drug distribution for competing device designs. The coupling of immunofluorescence on tissue sections and computational modeling with an understanding of the vascular response to device implantation is an important step towards filling this void. We can now differentiate drug eluting systems based not simply on payload or time of release but on net tissue spatial delivery. In doing so, it is possible to anticipate target effects rather than focus on target stimuli."

CBSET President and CEO Peter Markham, a study investigator, stated, "This paradigm shift in preclinical assessment of stents creates an opportunity for the medical device industry to optimize endovascular drug delivery therapies to coronary and peripheral lesions."

David Kandzari, MD, added, "This preclinical demonstration that stent deployment of microcrystalline drug in combination with a rapidly absorbable polymer, such as with MiStent (Micell Technologies, Inc.), results in more uniform drug dosing that could lead to more rapid and uniform healing across the treated segment." Dr. Kandzari is Director of Interventional Cardiology and Chief Scientific Officer at Piedmont Heart Institute, in Atlanta, Georgia.