Tzafriri AR, Markham PM, LaRochelle AW, Spognardi AM, Bailey L, Cohen I, Elmalak O, Richter Y, Edelman ER. ‘Ridaforolimus Eluting Stents with Customizable Diffusion Controlled Release Kinetics and Tissue Uptake.’ Poster presentation at: Cardiovascular Research Technologies (CRT); 2016 Feb 20-23; Washington, DC.
Drug release from spray coatings applied to cylindrical stents is difficult to customize due to intermixing of successively coated layers.
Methods and Results
Flat sheets of electropolished L-605 Cobalt Chromium alloy were spray coated with a solution of Ridaforolimus and two polymers, folded and welded into cylinders (3.0×17mm) and sterilized. Ridaforolimus-eluting stents (RES; Medinol, Israel) were incubated in vitro (≤90d) or implanted (≤456d) in porcine coronary arteries (1 stent/artery, 1.1-1.3:1 B:A) and drug quantified by LC/MS/MS. Ridaforolimus release from RES was computationally modeled as a diffusion process based on layer thicknesses and compositions, and coupled to published equations of tissue binding and diffusion to predict arterial tissue content.
In vitro release of Ridaforolimus from 11 distinct RES formulations formed by single or multiple spray coat applications of the same composition spanned a dynamic range that was fully matched by the model with a composition-dependent diffusivity. The calibrated computational model accurately predicted in vitro drug release of the 3 multi-layer RES formulations, including the clinically relevant BioNIR formulation which incorporates a rate-lmiting polymer layer sandwitched between two drug loaded layers. Implanted BioNIR stents release 98.1% of the initial Ridaforlimus load within 180d, providing a near constant tissue content of drug (2.2 ng/mg) between 1-30d that slowly declined to trace levels by 456d as FKBP12 bound drug dissociated and diffused out of the artery wall.
Coating flat stationary metal sheets prior to rolling provided customizable diffusion-controlled Ridaforolimus delivery based on designed coating thicknesses and compositions.