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含紫杉醇的新型壳聚糖/转基因纳米结构的体外亚细胞定位及体内疗效

The in vitro sub-cellular localization and in vivo efficacy of novel chitosan/GMO nanostructures containing paclitaxel.

作者信息

Trickler W J, Nagvekar A A, Dash A K

机构信息

Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, 2500 California Plaza, Omaha, Nebraska 68178, USA.

出版信息

Pharm Res. 2009 Aug;26(8):1963-73. doi: 10.1007/s11095-009-9911-5. Epub 2009 May 20.

Abstract

PURPOSE

To determine the in vitro sub-cellular localization and in vivo efficacy of chitosan/GMO nanostructures containing paclitaxel (PTX) compared to a conventional PTX treatment (Taxol).

METHODS

The sub-cellular localization of coumarin-6 labeled chitosan/GMO nanostructures was determined by confocal microscopy in MDA-MB-231 cells. The antitumor efficacy was evaluated in two separate studies using FOX-Chase (CB17) SCID Female-Mice MDA-MB-231 xenograph model. Treatments consisted of intravenous Taxol or chitosan/GMO nanostructures with or without PTX, local intra-tumor bolus of Taxol or chitosan/GMO nanostructures with or without PTX. The tumor diameter and animal weight was monitored at various intervals. Histopathological changes were evaluated in end-point tumors.

RESULTS

The tumor diameter increased at a constant rate for all the groups between days 7-14. After a single intratumoral bolus dose of chitosan/GMO containing PTX showed significant reduction in tumor diameter on day 15 when compared to control, placebo and intravenous PTX administration. The tumor diameter reached a maximal decrease (4-fold) by day 18, and the difference was reduced to approximately 2-fold by day 21. Qualitatively similar results were observed in a separate study containing PTX when administered intravenously.

CONCLUSION

Chitosan/GMO nanostructures containing PTX are safe and effective administered locally or intravenously. Partially supported by DOD Award BC045664.

摘要

目的

与传统紫杉醇治疗(泰素)相比,确定含紫杉醇(PTX)的壳聚糖/转基因纳米结构的体外亚细胞定位及体内疗效。

方法

通过共聚焦显微镜在MDA-MB-231细胞中确定香豆素-6标记的壳聚糖/转基因纳米结构的亚细胞定位。在两项独立研究中,使用FOX-Chase(CB17)SCID雌性小鼠MDA-MB-231异种移植模型评估抗肿瘤疗效。治疗包括静脉注射泰素或含或不含PTX的壳聚糖/转基因纳米结构,局部肿瘤内推注泰素或含或不含PTX的壳聚糖/转基因纳米结构。在不同时间间隔监测肿瘤直径和动物体重。对终点肿瘤进行组织病理学变化评估。

结果

在第7至14天期间,所有组的肿瘤直径均以恒定速率增加。与对照组、安慰剂组和静脉注射PTX给药相比,单次瘤内推注含PTX的壳聚糖/转基因纳米结构在第15天时肿瘤直径显著减小。到第18天时肿瘤直径达到最大减小(4倍),到第21天时差异减小至约2倍。在另一项含PTX静脉给药的独立研究中观察到定性相似的结果。

结论

含PTX的壳聚糖/转基因纳米结构局部或静脉给药安全有效。部分得到国防部BC045664奖的支持。

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