Intratracheal Versus Intravenous Liposomal Delivery of siRNA, Antisense Oligonucleotides and Anticancer Drug
Intratracheal Versus Intravenous Liposomal Delivery of siRNA, Antisense Oligonucleotides and Anticancer Drug
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DOI：
10.1007/s11095-008-9755-4
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发表时间：
2009-02-01
影响因子：
3.7
通讯作者：
Minko, Tamara
中科院分区：
文献类型：
--
作者：
Garbuzenko, Olga B.;Saad, Maha;Minko, Tamara
目的。比较阿霉素（DOX）、反义寡核苷酸（ASO）和小干扰RNA （siRNA）的全身静脉和局部气管内给药情况。“中性”和阳离子脂质体用于递送DOX、ASO和siRNA。通过动态光散射、ζ电位和原子力显微镜对脂质体进行了表征。用共聚焦显微镜研究了人肺癌细胞中DOX、ASO和siRNA的细胞内化。用裸鼠建立人肺癌原位模型进行了体内实验。脂质体在体外提供了DOX， ASO和siRNA的有效细胞内递送。与全身给药相比，两种类型的脂质体经气管内给药可导致更高的峰值浓度和更长的脂质体、DOX、ASO和siRNA在肺部的滞留时间。研究发现，局部气管内给予DOX脂质体治疗肺癌比静脉给药和游离DOX脂质体治疗肺癌更有效。本研究概述了与全身给药相比，局部气管内给药脂质体治疗肺癌的明显优势。
Purpose. To compare systemic intravenous and local intratracheal delivery of doxorubicin (DOX), antisense oligonucleotides (ASO) and small interfering RNA (siRNA).Methods. "Neutral" and cationic liposomes were used to deliver DOX, ASO, and siRNA. Liposomes were characterized by dynamic light scattering, zeta-potential, and atomic force microscopy. Cellular internalization of DOX, ASO and siRNA was studied by confocal microscopy on human lung carcinoma cells. In vivo experiments were carried out on nude mice with an orthotopic model of human lung cancer.Results. Liposomes provided for an efficient intracellular delivery of DOX, ASO, and siRNA in vitro. Intratracheal delivery of both types of liposomes in vivo led to higher peak concentrations and much longer retention of liposomes, DOX, ASO and siRNA in the lungs when compared with systemic administration. It was found that local intratracheal treatment of lung cancer with liposomal DOX was more efficient when compared with free and liposomal DOX delivered intravenously.Conclusions. The present study outlined the clear advantages of local intratracheal delivery of liposomal drugs for the treatment of lung cancer when compared with systemic administration of the same drug.