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采用雾化友好型纳米乳同时肺部给予塞来昔布和柚皮苷:一种用于治疗肺癌的靶向给药装置。

Simultaneous pulmonary administration of celecoxib and naringin using a nebulization-friendly nanoemulsion: A device-targeted delivery for treatment of lung cancer.

机构信息

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK.

出版信息

Expert Opin Drug Deliv. 2022 May;19(5):611-622. doi: 10.1080/17425247.2022.2076833. Epub 2022 May 19.

Abstract

BACKGROUND

Lung cancer is a principal cause of death worldwide, and its treatment is very challenging. Nebulization offers a promising means of targeting drugs to their site of action in the lung.

RESEARCH DESIGN AND METHODS

In the present study, nebulizable oil in water nanoemulsion formulations was co-loaded with naringin/celecoxib and tested for pulmonary administration by different nebulizer types.

RESULTS

The translucent appearance of nanoemulsion formulations was revealed, with particle size (75-106 nm), zeta potential (-3.42 to -4.86 mV), and controlled release profiles for both drugs. The nanoemulsions showed favorable stability profiles and superior cytotoxicity on A549 lung cancer cells. Aerosolization studies on the selected nanoemulsion formulation revealed its high stability during nebulization, with the generation of an aerosol of small volume median diameter and mass median aerodynamic diameter lower than 5 µm. Moreover, it demonstrated considerable safety and bioaccumulation in lung tissues, in addition to accumulation in the brain, liver, and bones, which are the main organs to which lung cancer metastasizes.

CONCLUSIONS

Nanoemulsion proved to be a promising nebulizable system, which paves the way for treatment of pulmonary diseases other than lung cancer.

摘要

背景

肺癌是全球主要的死亡原因之一,其治疗极具挑战性。雾化给药为将药物靶向作用于肺部提供了一种很有前途的手段。

研究设计与方法

本研究将柚皮苷/塞来昔布共载入微乳中,并通过不同的雾化器类型对其肺部给药进行了测试。

结果

微乳制剂呈现半透明外观,粒径(75-106nm)、Zeta 电位(-3.42 至-4.86mV)以及两种药物的控释特征。微乳显示出良好的稳定性,并对 A549 肺癌细胞具有优越的细胞毒性。对选定的微乳制剂的雾化研究表明,其在雾化过程中具有很高的稳定性,生成的气溶胶体积中值直径和质量中值空气动力学直径均低于 5μm。此外,它在肺部组织中表现出相当的安全性和生物累积性,同时也在大脑、肝脏和骨骼等主要转移部位累积,这些部位是肺癌转移的主要部位。

结论

微乳证明是一种很有前途的可雾化系统,为治疗除肺癌以外的肺部疾病铺平了道路。

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