Fluorescence imaging and phototoxicity effects of new formulation of chlorin e6-polyvinylpyrrolidone
Fluorescence imaging and phototoxicity effects of new formulation of chlorin e6-polyvinylpyrrolidone
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DOI：
10.1016/j.jphotobiol.2006.02.002
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发表时间：
2006-08-01
影响因子：
5.4
通讯作者：
Olivo, Malini
中科院分区：
文献类型：
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作者：
Chin, William Wei Lim;Lau, Weber Kam On;Olivo, Malini
在低分化的人膀胱癌鼠模型上进行由二氢卟酚e6（Ce 6）和聚乙烯吡咯烷酮（PVP）的三钠盐的复合物组成的二氢卟酚的新制剂在光动力疗法（PDT）和荧光诊断中的效率的评估，具体目的如下：（i）定性评价人膀胱肿瘤中的荧光积累，（ii）使用组织提取技术和荧光成像技术测定Ce 6-PVP的荧光分布，（iii）比较Ce 6、Ce 6-PVP和Photofrin在裸鼠皮肤中的荧光分布，（iv）研究PDT中不同参数（药物-光间隔、药物剂量、辐照注量率和总光注量）引起的光毒性。Ce 6-PVP制剂的荧光通过荧光成像测量或通过从显示类似分布趋势的组织中化学提取来确定。我们的结果表明，Ce 6-PVP制剂具有较低的体内光毒性作用相比，单独的Ce 6。光毒性显示出强烈的依赖性的药物和光剂量以及药物-光的间隔。在PDT中，Ce 6-PVP化合物在200 J/cm（2）的1 h药物-光照间隔下毒性最大，而Ce 6单独在1和3 h药物-光照间隔下的光剂量超过50 J/cm（2）时毒性最大。我们还证实，与单独的Ce 6或Photofrin相比，Ce 6-PVP具有更快的清除率。这消除了长期光敏性预防措施的需要。总之，Ce 6-PVP制剂似乎是用于荧光成像以及用于光动力治疗的有前途的光敏剂。(c)2006 Elsevier B. V.保留所有权利。
Evaluations of the efficiency of a new formulation of chlorin consisting of a complex of trisodium salt chlorin e6 (Ce6) and polyvinylpyrrolidone (PVP) in photodynamic therapy (PDT) and fluorescence diagnosis was performed on poorly differentiated human bladder carcinoma murine model with the following specific aims: (i) to qualitatively evaluate the fluorescence accumulation in human bladder tumor, (ii) to determine fluorescence distribution of Ce6-PVP using the tissue extraction technique and fluorescence imaging technique, (iii) to compare the fluorescence distribution of Ce6, Ce6-PVP and Photofrin in skin of nude mice, and (iv) to investigate phototoxicity caused by different parameters (drug-light interval, drug dose, irradiation fluence rate and total light fluence) in PDT. The fluorescence of the Ce6-PVP formulation was determined either by fluorescence imaging measurements or by chemical extraction from the tissues displaying similar trends of distribution. Our results demonstrated that the Ce6-PVP formulation possesses less in vivo phototoxic effect compared to Ce6 alone. The phototoxicity revealed a strong dependence on the drug and light dosimetry as well as on the drug-light interval. In PDT, the Ce6-PVP compound was most toxic at the 1 h drug-light interval at 200 J/cm(2), while Ce6 alone was most toxic at a light dose of more that 50 J/cm(2) at the 1 and 3 h drug-light interval. We also confirmed that Ce6-PVP has a faster clearance compared to Ce6 alone or Photofrin. This eliminates the need for long-term photosensitivity precautions. In conclusion, the Ce6-PVP formulation seems to be a promising photosensitizer for fluorescence imaging as well as for photodynamic treatment. (c) 2006 Elsevier B.V. All rights reserved.