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Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings.

ABSTRACT: BACKGROUND:Innovations in drug eluting stent designs make it increasingly important to develop models for differentiating performance through spatial definition of drug, receptor binding and cell state. METHODS:Two designs of sirolimus analog eluting stents were implanted into porcine coronary arteries for 28, 60 or 90?days (n?=?9/time point), durable coating (Xience) and deployable absorbable coating (MiStent). Explanted arteries were evaluated for drug content (n?=?3/time point) by LC-MS/MS and for drug and target protein (mTOR) distributions by immunofluorescence (IF, n?=?6/time point). A computational model was developed to predict drug release and arterial distribution maps. RESULTS:Both stents released the majority of drug load by 28?days, with different tissue retention efficiencies (91.4?±?4.9% MiStent versus 21.5?±?1.9% Xience, P?98.5% of deployed drug remains crystalline through 90?days. Immunofluorescence and computational modeling showed peristrut drug localization for both stents, with similar peaks, but high interstrut levels only at sites of coating deployment from the absorbable coating. Co-localization of mTOR-IF with drug-IF for both devices showed persistent drug effects, though with differential drug-receptor pharmacokinetics. CONCLUSIONS:Immunofluorescence and computational modeling provide insights into drug distribution and binding status that can help differentiate drug delivery technologies. Herein we found that tissue deployment of slow dissolving crystalline drug particles results in temporally and spatially more uniform drug delivery to interstrut zones that might otherwise be under-dosed without excess peristrut drug.

SUBMITTER: Tzafriri AR

PROVIDER: S-EPMC5847480 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings.

Tzafriri Abraham R AR Garcia-Polite Fernando F Li Xiaojian X Keating John J Balaguer Josep-Maria JM Zani Brett B Bailey Lynn L Markham Peter P Kiorpes Timothy C TC Carlyle Wenda W Edelman Elazer R ER

Journal of controlled release : official journal of the Controlled Release Society 20180205

<h4>Background</h4>Innovations in drug eluting stent designs make it increasingly important to develop models for differentiating performance through spatial definition of drug, receptor binding and cell state.<h4>Methods</h4>Two designs of sirolimus analog eluting stents were implanted into porcine coronary arteries for 28, 60 or 90 days (n = 9/time point), durable coating (Xience) and deployable absorbable coating (MiStent). Explanted arteries were evaluated for drug content (n = 3/time point) ...[more]

PMID: 29421608

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Project description:AimsIn-stent chronic total occlusion (IS-CTO) represents a unique challenge for percutaneous coronary intervention. Whether the optimal treatment for IS-CTO is angioplasty with paclitaxel-coated balloons (PCBs) or repeat stenting with drug-eluting stents (DESs) is unclear. We aimed to evaluate the long-term clinical outcome of PCB angioplasty and DES repeat stenting for DES IS-CTO.MethodsWe retrospectively included patients with DES IS-CTO who underwent successful PCB angioplasty or DES repeat stenting from January 2016 to December 2019. The primary endpoints were major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, and target lesion revascularization (TLR). Cox proportional hazards model was performed to compare the risk of MACEs between PCB angioplasty and DES repeat stenting, and to further explore the prognostic factors of patients with DES IS-CTO.ResultsA total of 214 patients with DES IS-CTO were enrolled: 78 patients (36.4%) treated with PCB and 136 patients (63.6%) treated with DES respectively. The median follow-up was 1160 days, and MACEs were observed in 28.2% of patients with PCB angioplasty versus 26.5% of patients with DES repeat stenting (P = 0.784), mainly driven by TLR (21.8% vs. 19.9%, P = 0.735). There was no significant difference in the risk of MACEs between the PCB group and the DES group (hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.64-2.46, P = 0.512). Multivariate Cox analysis revealed that chronic kidney disease and ≥ 3 stent layers in the lesion were independent predictors of MACEs, while switching to another antiproliferative drug was an independent protective factor (all P < 0.05).ConclusionsPCB angioplasty was an effective alternative treatment strategy for DES IS-CTO, which had similar long-term outcomes to DES repeat stenting in contemporary practice, but both were accompanied by a high rate of long-term MACEs. Improving the poor prognosis of patients with DES IS-CTO remains a challenge.

Dataset Information

Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings.

Publications

Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings.

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