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低水平 LED 光动力疗法,使用负载姜黄素的四醚脂质体。

Low level LED photodynamic therapy using curcumin loaded tetraether liposomes.

机构信息

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany.

出版信息

Eur J Pharm Biopharm. 2018 May;126:233-241. doi: 10.1016/j.ejpb.2017.10.005. Epub 2017 Oct 7.

Abstract

Oncological use of photodynamic therapy is an evolving field in cancer therapeutics. Photosensitisers are prone to accumulation inside healthy tissues causing undesirable effects. To avoid this, we have developed tetraether lipid liposomal formulations containing curcumin which is a naturally occurring anti-cancer substance and deemed to be safe towards healthy cells. Upon excitation with light at a specific wavelength, curcumin produces reactive oxygen species (ROS) in presence of oxygen, thereby exhibiting a cytotoxic effect towards the surrounding tissues, giving a total control on the onset of therapy. In our study, we examined two different liposomal formulations wherein curcumin is encapsulated within the hydrophobic milieu with the intent to increase its bioavailability. Hydrodynamic diameter, surface charge, stability, morphology and haemocompatibility of the liposomes were studied. The results confirmed the formation of stable nanometre range liposomal vesicles (200-220 nm) containing curcumin which were haemocompatible with coagulation time less than 50 s and a haemolytic potential below 40%. Increased ROS generation post irradiation (>50% compared to un-irradiated samples) was confirmed using fluorescence spectroscopy. The efficiency and selectivity of the PDT was demonstrated by assessing their viability post irradiation and by qualitative analysis using confocal microscopy showing nuclear perforation induced by PDT. Photo-destructive effects of PDT on the microvasculature were studied in vivo using chick chorioallantoic membrane model (CAM). Considerable phototoxicity could be observed in the irradiated area of the CAM 30 min post irradiation. Phototoxic effects in vitro (in SK-OV-3 and PCS-100-020™) and in vivo (in chorioallantoic membrane model) in combination with a novel custom manufactured LED irradiating device showed a formulation dependant selective photodynamic effect of the curcumin liposomes.

摘要

光动力疗法在癌症治疗中是一个不断发展的领域。光敏剂容易在健康组织中积累,从而产生不良影响。为了避免这种情况,我们开发了含有姜黄素的四醚脂质脂质体制剂,姜黄素是一种天然存在的抗癌物质,被认为对健康细胞是安全的。在特定波长的光激发下,姜黄素在氧气存在下产生活性氧物质(ROS),从而对周围组织表现出细胞毒性作用,从而完全控制治疗的开始。在我们的研究中,我们检查了两种不同的脂质体制剂,其中姜黄素被包裹在疏水环境中,目的是增加其生物利用度。研究了脂质体的水动力学直径、表面电荷、稳定性、形态和血液相容性。结果证实了形成了含有姜黄素的稳定纳米范围脂质体囊泡(200-220nm),这些脂质体具有血液相容性,凝血时间小于 50 秒,溶血潜能低于 40%。使用荧光光谱证实了辐照后 ROS 生成增加(与未辐照样品相比增加超过 50%)。通过评估辐照后它们的活力和使用共聚焦显微镜进行定性分析来证明 PDT 的效率和选择性,显示 PDT 诱导的核穿孔。使用鸡胚绒毛尿囊膜模型(CAM)在体内研究了 PDT 对微血管的光破坏作用。辐照后 30 分钟,在 CAM 的辐照区域可以观察到相当大的光毒性。体外(在 SK-OV-3 和 PCS-100-020™)和体内(在绒毛尿囊膜模型)的光毒性与新型定制制造的 LED 辐照装置相结合,显示了姜黄素脂质体的制剂依赖性选择性光动力作用。

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