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二氢卟吩e6-聚乙烯吡咯烷酮制剂在光动力疗法中的潜在应用。

The potential application of chlorin e6-polyvinylpyrrolidone formulation in photodynamic therapy.

作者信息

Chin William Wei Lim, Heng Paul Wan Sia, Bhuvaneswari Ramaswamy, Lau Weber Kam On, Olivo Malini

机构信息

Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.

出版信息

Photochem Photobiol Sci. 2006 Nov;5(11):1031-7. doi: 10.1039/b605772a. Epub 2006 Sep 21.

DOI:10.1039/b605772a
PMID:17077899
Abstract

Much research has been focused on developing effective drug delivery systems for the preparation of chlorins as potential photosensitizers for PDT. This report describes the evaluation of a new water-soluble formulation of chlorin e6 consisting of a complex of trisodium salt chlorin e6 and polyvinylpyrrolidone (Ce6-PVP) for application in photodynamic therapy (PDT) with 2 specific aims: (i) to investigate its fluorescence kinetics in skin, normal and tumor tissue after intravenous administration, and (ii) to investigate its PDT efficacy. Our results demonstrate that this new formulation possesses photosensitizing properties with rapid accumulation in tumor tissue observed within 1 h after intravenous administration. Although high selectivity in tumor tissue was found between the period of 3 and 6 h, the efficacy of Ce6-PVP mediated PDT was best at 1 h drug-light interval. It is suggested that, the extent of tumor necrosis post PDT is dependent on the plasma concentration of Ce6-PVP, implying a vascular mediated cell death mechanism. A faster clearance rate of Ce6-PVP from the skin of nude mice was observed compared to Ce6. The new formulation of Ce6-PVP seems to show promise as an effective therapeutic agent.

摘要

许多研究都集中在开发有效的药物递送系统,用于制备二氢卟吩作为光动力疗法(PDT)的潜在光敏剂。本报告描述了一种新的水溶性二氢卟吩e6制剂的评估,该制剂由二氢卟吩e6三钠盐与聚乙烯吡咯烷酮的复合物(Ce6-PVP)组成,用于光动力疗法(PDT),有两个特定目的:(i)研究静脉给药后其在皮肤、正常组织和肿瘤组织中的荧光动力学,以及(ii)研究其光动力疗法疗效。我们的结果表明,这种新制剂具有光敏特性,静脉给药后1小时内可观察到在肿瘤组织中快速积累。虽然在3至6小时期间发现肿瘤组织具有高选择性,但Ce6-PVP介导的光动力疗法疗效在药物-光照间隔为1小时时最佳。有人提出,光动力疗法后肿瘤坏死的程度取决于Ce6-PVP的血浆浓度,这意味着一种血管介导的细胞死亡机制。与Ce6相比,观察到Ce6-PVP从裸鼠皮肤中的清除率更快。Ce6-PVP的新制剂似乎有望成为一种有效的治疗剂。

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