Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug

Abstract

Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug more evenly within the intimal area rather than concentrating drug around the stent struts and for its ability to match coating erosion with drug release. The coating consisted of absorbable poly-lactide-co-glycolic acid (PLGA) and crystalline sirolimus deposited by a dry-powder electrostatic process. The AC-SES demonstrated enhanced drug stability under simulated use conditions and consistent drug delivery balanced with coating erosion in a porcine coronary implant model. The initial drug burst was eliminated and drug release was sustained after implantation. The coating was absorbed within 90 days. Following implantation into porcine coronary arteries the AC-SES coating is distributed in the surrounding intimal tissue over the course of several weeks. Computational modeling of drug delivery characteristics demonstrates how distributed coating optimizes the load of drug immediately around each stent strut and extends drug delivery between stent struts. The result was a highly efficient arterial uptake of drug with superior performance to a clinical bare metal stent (BMS). Neointimal thickness (0.17±0.07 mm vs. 0.28±0.11 mm) and area percent stenosis (22±9% vs. 35±12%) were significantly reduced (p<0.05) by the AC-SES compared to the BMS 30 days after stent implantation in an overlap configuration in porcine coronary arteries. Inflammation was significantly reduced in the AC-SES compared to the BMS at both 30 and 90 days after implantation. Biocompatible, rapidly absorbable stent coatings enable the matching of drug release with coating erosion and provide for the controlled migration of coating material into tissue to reduce vicissitudes in drug tissue levels, optimizing efficacy and reducing potential toxicity.

A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine

“…The AC-SES results showed acceptable drug stability under simulated conditions and consistent drug delivery in a porcine coronary implant model. 25 There have also been a significant number of research efforts to identify whether corrodible substances may be applied as low toxic biodegradable cardiovascular implants. Corrodible iron stents were prepared from pure iron and laser cut with a stent design similar to a commercially available used stent.…”

<i>In vitro</i> pharmacokinetics of sirolimus-coated stent for tracheal stenosis

“…Previous studies suggested that the mechanisms of in vitro drug release in DES were mainly based on drug diffusion and degradation of the stent polymer [20,21]. Pires et al [22] found that there was a quick release period and a subsequent slow release period of drugs from DES in vitro.…”

Drug deposition in coronary arteries with overlapping drug-eluting stents

“…In those cases, the time-dependence of drug release [46] and the process of drug binding to tissue proteins will more accurately determine the ultimate drug uptake [47, 48]. Assuming a more dynamic environment of biological host species, vascular response both to the intravascular implant and depleted drug in terms of intimal hyperplasia and thrombosis should also be included in future numerical models to better assess the efficacy of new generations of drug-eluting implants [49] in more sophisticated clinical routines such as overlap [50, 51]. Developing such an intricate model entails further in vivo studies to acquire empirical factors of the biological response of the artery to develop a multi-scale, multi-modal tool.…”