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卡铂在视网膜母细胞瘤小鼠模型中的离子电渗给药

Iontophoretic delivery of carboplatin in a murine model of retinoblastoma.

作者信息

Hayden Brandy, Jockovich Maria-Elena, Murray Timothy G, Kralinger Martina T, Voigt Monika, Hernandez Eleut, Feuer William, Parel Jean-Marie

机构信息

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida 33101, USA.

出版信息

Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3717-21. doi: 10.1167/iovs.06-0365.

Abstract

PURPOSE

To evaluate the efficacy and dose-response of transcorneoscleral Coulomb controlled iontophoresis (CCI) of carboplatin in the treatment of retinal tumors of a murine model of retinoblastoma.

METHODS

Thirty 6-week-old LHBETATAG mice underwent a total of six, serial iontophoretic treatments administered two times per week using a current density of 2.57 mA/cm2 for 5 minutes. Fourteen animals received carboplatin treatments at concentrations of 1.4, 7.0, 10.0, or 14.0 mg/mL without current. Ten control mice underwent treatment with balanced saline solution.

RESULTS

A dose-dependent inhibition of intraocular tumor was observed after repetitive iontophoretic treatment. At carboplatin concentrations of 7 mg/mL, 50% of the treated eyes (4/8) exhibited tumor control. No corneal toxicity was observed in eyes treated at carboplatin concentrations under 10 mg/mL.

CONCLUSIONS

CCI delivery of carboplatin safely and effectively controls intraocular tumors in a dose-dependent manner in this murine model of retinoblastoma. CCI is a noninvasive, painless option for the focal delivery of carboplatin. However, further clinical and laboratory research is needed before this method of drug delivery is available for children with retinoblastoma.

摘要

目的

评估经角膜巩膜库仑控制离子电渗疗法(CCI)递送卡铂治疗视网膜母细胞瘤小鼠模型视网膜肿瘤的疗效和剂量反应。

方法

30只6周龄的LHBETATAG小鼠,每周接受两次共6次连续离子电渗疗法治疗,电流密度为2.57 mA/cm²,持续5分钟。14只动物接受浓度为1.4、7.0、10.0或14.0 mg/mL的卡铂治疗,无电流。10只对照小鼠接受平衡盐溶液治疗。

结果

重复离子电渗疗法治疗后观察到眼内肿瘤的剂量依赖性抑制。在卡铂浓度为7 mg/mL时,50%的治疗眼(4/8)实现了肿瘤控制。在卡铂浓度低于10 mg/mL治疗的眼中未观察到角膜毒性。

结论

在该视网膜母细胞瘤小鼠模型中,CCI递送卡铂以剂量依赖性方式安全有效地控制眼内肿瘤。CCI是卡铂局部递送的一种非侵入性、无痛的选择。然而,在这种药物递送方法可用于视网膜母细胞瘤患儿之前还需要进一步的临床和实验室研究。

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