Improved formulation of photosensitizer chlorin e6 polyvinylpyrrolidone for fluorescence diagnostic imaging and photodynamic therapy of human cancer
Improved formulation of photosensitizer chlorin e6 polyvinylpyrrolidone for fluorescence diagnostic imaging and photodynamic therapy of human cancer
复制标题
DOI：
10.1016/j.ejpb.2008.02.013
复制
发表时间：
2008-08-01
影响因子：
4.9
通讯作者：
Olivo, Malini
中科院分区：
文献类型：
--
作者：
Chin, William Wei Lim;Heng, Paul Wan Sia;Olivo, Malini
研究了光敏剂二氢卟酚e6（Ce 6）与亲水性聚合物聚乙烯吡咯烷酮（PVP）的组合的改进制剂在癌症的荧光诊断和光动力学治疗（PDT）中的潜在临床应用。本研究报告了与二甲亚砜（DMSO）相比，使用或不使用PVP递送Ce 6的临床前生物分布和疗效。并对Ce 6-PVP的人体安全性和荧光药理作用进行了评价。生物分布结果显示，与其他制剂相比，Ce 6-PVP具有更高的肿瘤与正常组织比率。从受试者操作特征曲线下的面积导出的灵敏度和特异性显示，制剂能够按以下顺序区分肿瘤与瘤周肌肉：Ce 6-PVP > Ce 6> Ce 6-DMSO。体外光动力学结果表明，Ce 6-PVP被发现诱导选择性光毒性白血病细胞相比，外周血单个核细胞。此外，发现Ce 6-PVP后1小时的体内光照射诱导更大的肿瘤坏死，而不引起动物毒性。在患者中，静脉给药后，与正常皮肤相比，在血管肉瘤病变中观察到Ce 6-PVP的优先蓄积。结论：PVP能显著提高肿瘤组织中Ce 6的浓度，提高PDT的治疗指数，且无明显毒副作用。在人体中也未观察到严重不良事件。(C)2008 Elsevier B. V.保留所有权利。
An improved formulation of the photosensitizer chlorin e6 (Ce6) in combination with the hydrophilic polymer polyvinylpyrrolidone (PVP) was investigated for its potential clinical applications in fluorescence diagnosis and photodynamic therapy (PDT) of cancer. This study reports the comparative preclinical biodistribution and efficacy of Ce6 delivered with or without PVP versus dimethyl sulfoxide (DMSO). The safety and fluorescence pharrnacokinetics of Ce6-PVP in humans was also accessed. Biodistribution results showed that Ce6-PVP had higher tumor to normal tissue ratio compared to the other formulations. The sensitivity and specificity derived from the area under the receiver operating characteristics curves showed that the formulations were able to discriminate tumor from peritumoral muscle in the following order: Ce6-PVP > Ce6 > Ce6-DMSO. In vitro PDT results showed that Ce6-PVP was found to induce selective phototoxicity in leukemic cells compared to peripheral mononuclear blood cells. In addition, in vivo light irradiation at I h after Ce6-PVP was found to induce greater tumor necrosis without causing animal toxicity. In patients, preferential accumulation of Ce6-PVP was observed in angiosarcoma lesions compared to normal skin following intravenous administration. In conclusion, PVP significantly enhanced the Ce6 concentration ill tumors compared with Ce6 alone and increased the therapeutic index of PDT without any side effects in animal model. No serious adverse events were observed ill human as well. (C) 2008 Elsevier B.V. All rights reserved.