Translational and Molecular Imaging Institute and Imaging Science Laboratories, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, New York 10029, United States.
Mol Pharm. 2010 Dec 6;7(6):2020-9. doi: 10.1021/mp100309y. Epub 2010 Nov 8.
Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy.
动脉粥样硬化是一种炎症性疾病，在西方国家造成了巨大的发病率和死亡率。为了提高糖皮质激素（PLP）的抗炎作用并降低其不良反应，开发了一种该药物的纳米医学脂质体制剂（L-PLP），并以 15mg/kg PLP 的剂量静脉内应用于动脉粥样硬化兔模型。由于动脉粥样硬化是一种全身性疾病，因此正在开发用于评估动脉粥样硬化斑块的新兴成像方式。（18）F-氟代脱氧葡萄糖正电子发射断层扫描和动态对比增强磁共振成像，这两种通常用于肿瘤学的方法，被用于纵向评估治疗效果。在给予单次 L-PLP 剂量后，早在 2 天即可观察到显著的抗炎作用，并且至少持续 7 天。在给予游离 PLP 的动物中未发现明显变化。血管壁中巨噬细胞密度的免疫组织化学分析证实了这些发现。总之，这项研究评估了一种有效的治疗动脉粥样硬化的双管齐下策略，包括对动脉粥样硬化斑块的纳米医学治疗以及应用非侵入性和临床批准的成像技术来监测药物输送和治疗反应。重要的是，我们在纳米医学治疗后在动脉粥样硬化病变中证明了前所未有的快速抗炎作用。
