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微泡辅助超声递送伊立替康:体外验证及临床前初步研究

Irinotecan delivery by microbubble-assisted ultrasound: in vitro validation and a pilot preclinical study.

作者信息

Escoffre J-M, Novell A, Serrière S, Lecomte T, Bouakaz A

机构信息

UMR Inserm U930, Université François-Rabelais de Tours , PRES Centre-Val de Loire Université, 37044 Tours, France.

出版信息

Mol Pharm. 2013 Jul 1;10(7):2667-75. doi: 10.1021/mp400081b. Epub 2013 May 28.

Abstract

Irinotecan is a powerful anticancer drug with severe systemic side effects that limit its clinical application. Drug-targeted delivery with noninvasive methods is required to enhance the drug concentration locally and to reduce these undesirable events. Microbubble-assisted ultrasound has become a promising method for noninvasive targeted drug delivery. The aim of this study is to evaluate the therapeutic effectiveness of in vitro and in vivo irinotecan delivery based on the combination of ultrasound and microbubbles. In the present study, in vitro results showed that the irinotecan treatment with microbubble-assisted ultrasound induced a significant decrease in cell viability of human glioblastoma cells. Moreover, using subcutaneous glioblastoma xenografts, the in vivo preclinical study in nude mice demonstrated that this therapeutic protocol led to a decrease in tumor growth and perfusion and an increase of tumor necrosis. The conclusions drawn from this study demonstrate the promising potential of this therapeutic approach for the anticancer targeted therapy.

摘要

伊立替康是一种强效抗癌药物,但具有严重的全身副作用,这限制了其临床应用。需要采用非侵入性方法进行药物靶向递送,以提高局部药物浓度并减少这些不良事件。微泡辅助超声已成为一种有前景的非侵入性靶向药物递送方法。本研究的目的是评估基于超声和微泡联合的伊立替康体内外递送的治疗效果。在本研究中,体外结果表明,微泡辅助超声联合伊立替康治疗可导致人胶质母细胞瘤细胞活力显著下降。此外,利用皮下胶质母细胞瘤异种移植模型,在裸鼠体内进行的临床前研究表明,该治疗方案可导致肿瘤生长和灌注减少以及肿瘤坏死增加。本研究得出的结论表明,这种治疗方法在抗癌靶向治疗方面具有广阔的应用前景。

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