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肺部给药后泡腾可吸入纳米颗粒的分布:一项体内研究。

Distribution of effervescent inhalable nanoparticles after pulmonary delivery: an in vivo study.

作者信息

Al-Hallak M H D Kamal, Sarfraz Muhammad K, Azarmi Shirzad, Roa Wilson H, Finlay Warren H, Rouleau Claude, Löbenberg Raimar

机构信息

Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2N8, Canada.

出版信息

Ther Deliv. 2012 Jun;3(6):725-34. doi: 10.4155/tde.12.42.

Abstract

BACKGROUND

Effervescent inhalable nanoparticles (NPs) have previously been shown to be a promising alternative to conventional lung cancer treatment in animals. This study investigates the biodistribution of effervescent inhalable NPs after a single dose administration via pulmonary route in lung cancer-bearing mice.

METHODS & RESULTS: Whole-body autoradiography and confocal laser-scanning microscopy (CLSM) were used to investigate the distribution of inhalable NPs loaded in an effervescent microcarrier. Inhalable doxorubicin-loaded NPs were tagged with 14C for whole-body autoradiography, or with fluorescein isothiocyanate for CLSM imaging. After pulmonary delivery, NPs were widely disseminated in the lungs with a long retention time (24 h). The heart was radioactivity free at all time points of the study. CLSM images showed that inhalable NPs were taken up by cells and that doxorubicin was released to the cell nuclei.

CONCLUSION

This is the first study to investigate the distribution of inhalable NPs in a lung cancer-bearing animal model. Inhalable NPs achieved deep lung deposition, were actively released from microcarrier particles, spread to different parts of the lung and released doxorubicin in vivo. These NP characteristics contribute to the efficacy of effervescent inhalable NPs as a lung cancer treatment.

摘要

背景

此前已表明,泡腾可吸入纳米颗粒(NPs)在动物模型中是传统肺癌治疗方法的一种有前景的替代方案。本研究调查了在荷肺癌小鼠中经肺部途径单次给药后泡腾可吸入NPs的生物分布情况。

方法与结果

使用全身放射自显影和共聚焦激光扫描显微镜(CLSM)来研究负载于泡腾微载体中的可吸入NPs的分布。将负载阿霉素的可吸入NPs用14C标记用于全身放射自显影,或用异硫氰酸荧光素标记用于CLSM成像。经肺部给药后,NPs在肺中广泛分布且保留时间长(24小时)。在研究的所有时间点,心脏均无放射性。CLSM图像显示可吸入NPs被细胞摄取,且阿霉素释放到细胞核中。

结论

这是第一项在荷肺癌动物模型中研究可吸入NPs分布的研究。可吸入NPs实现了肺部深部沉积,从微载体颗粒中主动释放,扩散到肺的不同部位并在体内释放阿霉素。这些NP特性有助于泡腾可吸入NPs作为肺癌治疗方法的疗效。

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