Background: The feasibility of intravascular lithotripsy (IVL) for modification of severe coronary artery calcification (CAC) was demonstrated in the Disrupt CAD I study (Disrupt Coronary Artery Di...

Safety and Effectiveness of Coronary Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Stenoses: The Disrupt CAD II Study.

https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.118.036531

Feasibility of Shockwave Coronary Intravascular Lithotripsy for the Treatment of Calcified Coronary Stenoses.

Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease.

Background: Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis r...

https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.119.044697?download=true

Mortality and Paclitaxel-Coated Devices: An Individual Patient Data Meta-Analysis.

Drug-eluting stents have revolutionised the treatment of coronary artery disease. These small medical devices have attracted much interest over the past decade from biologists, clinicians, engineers and mathematicians alike. This article provides a comprehensive review of the modelling of drug release from arterial stents and the subsequent drug transport through arterial tissue, and acts as a useful reference equally for those who are already involved in drug-eluting stents research and for those who are starting out in the field. Assembled in this review are the main models of drug release and arterial drug transport that have been published in the literature to date. Many of the models presented in this paper have evolved from drug transport models in other applications. Furthermore, the ideas presented in this review may also be extended to other drug-delivery applications, such as drug coated balloons, transdermal patches and therapeutic contact lenses.

A decade of modelling drug release from arterial stents.

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis

Background Calcific atherosclerosis is a major challenge to intraluminal drug delivery in peripheral artery disease (PAD). Objectives We evaluated the effects of orbital atherectomy on intraluminal paclitaxel delivery to human peripheral arteries with substantial calcified plaque. Methods Diagnostic angiography and 3-D rotational imaging of five fresh human lower limbs revealed calcification in all main arteries. The proximal or distal segment of each artery was treated using an orbital atherectomy system (OAS) under simulated blood flow and fluoroscopy. Explanted arterial segments underwent either histomorphometric assessment of effect or tracking of 14 C-labeled or fluorescent–labeled paclitaxel. Radiolabeled drug quantified bulk delivery and fluorescent label established penetration of drug over finer spatial domain in serial microscopic sections. Results were interpreted using a mathematical model of binding-diffusion mediated arterial drug distribution. Results Lesion composition affected paclitaxel absorption and distribution in cadaveric human peripheral arteries. Pretreatment imaging calcium scores in control femoropopliteal arterial segments correlated with a log-linear decline in the bulk absorption rate-constant of 14 C-labeled, declining 5.5-fold per calcified quadrant (p = 0.05, n = 7). Compared to controls, OAS-treated femoropopliteal segments exhibited 180 μm thinner intima (p  Conclusions These data illustrate that calcified plaque limited intravascular drug delivery, and controlled OAS treatment of calcific plaques resulted in greater drug permeability and improved adjunct drug delivery to diseased arteries.

A mass transfer model of temporal drug deposition in artery walls

The
focus of this paper is to propose, model, and characterize a means of
accelerating the rate of delivery of therapeutic drugs to human tissues. The
investigated means is a pressurized, permeable-walled balloon filled with a
homogeneous mixture of the drug and the carrier fluid. The fluid mixture,
driven by pressure, traverses the thickness of the balloon wall through
laser-drilled pores. The number and deployment of the pores can be controlled to
a high degree of precision. As a consequence, the wall of the balloon can be
regarded as a homogeneous porous medium, and the traversing fluid flow can be
analyzed by means of porous media models. When the balloon is in intimate
contact with the surface of a tissue bed, the therapeutic fluid flows in series
as it passes through the balloon wall and penetrates the tissue. The flow rate
can be controlled by proper selection of the balloon permeability, the
viscosity of the flowing medium, and the pressure internal to the balloon. The
delivered concentration of the drug was predicted by coupling the present
balloon-focused theory with a previously developed tissue-bed model that
includes both diffusion and advection processes. The tribologic interaction of
the pressurized balloon with an artery wall was investigated experimentally to
assess the possible formation of aneurysms.

/pdf/controlling-the-rate-of-penetration-of-a-therapeutic-drug-15gahypmhb.pdf

Robert Kohler

Papers

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis

A mass transfer model of temporal drug deposition in artery walls

Controlling the rate of penetration of a therapeutic drug into the wall of an artery by means of a pressurized balloon

A Model of Drug Deposition Within Artery Walls