A Thermoresponsive Bubble-Generating Liposomal System for Triggering Localized Extracellular Drug Delivery
A Thermoresponsive Bubble-Generating Liposomal System for Triggering Localized Extracellular Drug Delivery
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DOI：
10.1021/nn304474j
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发表时间：
2013-01-01
期刊：
影响因子：
17.1
通讯作者：
Sung, Hsing-Wen
中科院分区：
文献类型：
--
作者：
Chen, Ko-Jie;Liang, Hsiang-Fa;Sung, Hsing-Wen
只有当肿瘤细胞受到最大程度的药物暴露时，化疗的治疗效果才是最佳的。为了增加瘤内药物浓度，从而提高化疗效果，提出了一种热响应性气泡生成脂质体系统来触发局部细胞外药物输送。该脂质体制剂的关键成分是封装的碳酸氢铵 (ABC)，它用于产生高效封装阿霉素 (DOX) 所需的跨膜梯度。在高温（42℃）下，ABC 分解产生 CO2 气泡，在脂质 Mayer 中产生可渗透缺陷，迅速释放 DOX 并立即增加局部药物浓度。由于产生的二氧化碳气泡具有高回声性，因此它们还可以增强超声成像。因此，这种用 ABC 封装的新型脂质体系统还可以提供监测温控药物输送过程的能力。
The therapeutic effectiveness of chemotherapy is optimal only when tumor cells are subjected to a maximum drug exposure. To increase the intratumoral drug concentration and thus the efficacy of chemotherapy, a thermoresponsive bubble-generating liposomal system is proposed for triggering localized extracellular drug delivery. The key component of this liposomal formulation is the encapsulated ammonium bicarbonate (ABC), which is used to create the transmembrane gradient needed for a highly efficient encapsulation of doxorubicin (DOX). At an elevated temperature (42 degrees C), decomposition of ABC generates CO2 bubbles, creating permeable defects in the lipid Mayer that rapidly release DOX and instantly increase the drug concentration locally. Because the generated CO2 bubbles are hyperechogenic, they also enhance ultrasound imaging. Consequently, this new liposomal system encapsulated with ABC may also provide an ability to monitor a temperature-controlled drug delivery process.