Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.
PLoS One. 2012;7(8):e43100. doi: 10.1371/journal.pone.0043100. Epub 2012 Aug 22.
The objective of this study was to optimize the physicodynamic conditions of polymeric system as a coating substrate for drug eluting stents against restenosis. As Nitric Oxide (NO) has multifunctional activities, such as regulating blood flow and pressure, and influencing thrombus formation, a continuous and spatiotemporal delivery of NO loaded in the polymer based nanoparticles could be a viable option to reduce and prevent restenosis. To identify the most suitable carrier for S-Nitrosoglutathione (GSNO), a NO prodrug, stents were coated with various polymers, such as poly (lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG) and polycaprolactone (PCL), using solvent evaporation technique. Full factorial design was used to evaluate the effects of the formulation variables in polymer-based stent coatings on the GSNO release rate and weight loss rate. The least square regression model was used for data analysis in the optimization process. The polymer-coated stents were further assessed with Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy analysis (FTIR), Scanning electron microscopy (SEM) images and platelet adhesion studies. Stents coated with PCL matrix displayed more sustained and controlled drug release profiles than those coated with PLGA and PEG. Stents coated with PCL matrix showed the least platelet adhesion rate. Subsequently, stents coated with PCL matrix were subjected to the further optimization processes for improvement of surface morphology and enhancement of the drug release duration. The results of this study demonstrated that PCL matrix containing GSNO is a promising system for stent surface coating against restenosis.
本研究旨在优化聚合物系统的物理动力学条件，将其作为药物洗脱支架的涂层基质，以对抗再狭窄。由于一氧化氮（NO）具有多种功能，如调节血流和血压，以及影响血栓形成，因此将负载在聚合物纳米颗粒中的 NO 进行持续和时空递释，可能是减少和预防再狭窄的可行选择。为了确定最适合的载体来负载 S-亚硝基谷胱甘肽（GSNO），一种 NO 前药，支架采用溶剂蒸发技术，用各种聚合物（如聚乳酸-共-羟基乙酸（PLGA）、聚乙二醇（PEG）和聚己内酯（PCL））进行涂层。全因子设计用于评估聚合物基支架涂层中制剂变量对 GSNO 释放率和失重率的影响。最小二乘回归模型用于优化过程中的数据分析。用差示扫描量热法（DSC）、傅里叶变换红外光谱分析（FTIR）、扫描电子显微镜（SEM）图像和血小板黏附研究进一步评估聚合物涂层支架。PCL 基质涂层的支架显示出比 PLGA 和 PEG 涂层的支架更持续和更受控的药物释放曲线。PCL 基质涂层的支架显示出最低的血小板黏附率。随后，对 PCL 基质涂层的支架进行了进一步的优化处理，以改善表面形貌和延长药物释放时间。这项研究的结果表明，载有 GSNO 的 PCL 基质是一种有前途的支架表面涂层系统，可用于对抗再狭窄。
