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可扩展生产及吸入式厄洛替尼纳米乳剂在非小细胞肺癌(NSCLC)中的体外疗效:增强疗效

Scalable Production and In Vitro Efficacy of Inhaled Erlotinib Nanoemulsion for Enhanced Efficacy in Non-Small Cell Lung Cancer (NSCLC).

作者信息

Chauhan Gautam, Wang Xuechun, Yousry Carol, Gupta Vivek

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt.

出版信息

Pharmaceutics. 2023 Mar 20;15(3):996. doi: 10.3390/pharmaceutics15030996.


DOI:10.3390/pharmaceutics15030996
PMID:36986858
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10054254/
Abstract

Non-small cell lung cancer (NSCLC) is a global concern as one of the leading causes of cancer deaths. The treatment options for NSCLC are limited to systemic chemotherapy, administered either orally or intravenously, with no local chemotherapies to target NSCLC. In this study, we have prepared nanoemulsions of tyrosine kinase inhibitor (TKI), erlotinib, using the single step, continuous manufacturing, and easily scalable hot melt extrusion (HME) technique without additional size reduction step. The formulated nanoemulsions were optimized and evaluated for their physiochemical properties, in vitro aerosol deposition behavior, and therapeutic activity against NSCLC cell lines both in vitro and ex vivo. The optimized nanoemulsion showed suitable aerosolization characteristics for deep lung deposition. The in vitro anti-cancer activity was tested against the NSCLC A549 cell line which exhibited 2.8-fold lower IC for erlotinib-loaded nanoemulsion, as compared to erlotinib-free solution. Furthermore, ex vivo studies using a 3D spheroid model also revealed higher efficacy of erlotinib-loaded nanoemulsion against NSCLC. Hence, inhalable nanoemulsion can be considered as a potential therapeutic approach for the local lung delivery of erlotinib to NSCLC.

摘要

非小细胞肺癌(NSCLC)作为癌症死亡的主要原因之一,是一个全球性问题。NSCLC的治疗选择仅限于口服或静脉注射的全身化疗,没有针对NSCLC的局部化疗方法。在本研究中,我们采用单步、连续制造且易于扩展的热熔挤出(HME)技术,制备了酪氨酸激酶抑制剂(TKI)厄洛替尼的纳米乳剂,无需额外的粒径减小步骤。对所制备的纳米乳剂进行了优化,并对其理化性质、体外气溶胶沉积行为以及对NSCLC细胞系的体外和离体治疗活性进行了评估。优化后的纳米乳剂显示出适合于肺部深部沉积的雾化特性。针对NSCLC A549细胞系测试了体外抗癌活性,与不含厄洛替尼的溶液相比,载有厄洛替尼的纳米乳剂的半数抑制浓度(IC)低2.8倍。此外,使用三维球体模型进行的离体研究也显示,载有厄洛替尼的纳米乳剂对NSCLC具有更高的疗效。因此,可吸入纳米乳剂可被视为将厄洛替尼局部递送至NSCLC肺部的一种潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/e2dd0cf35021/pharmaceutics-15-00996-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/2ca45a8d6a0e/pharmaceutics-15-00996-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/55c756b0872a/pharmaceutics-15-00996-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/650e7d8a6b08/pharmaceutics-15-00996-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/11b022f74360/pharmaceutics-15-00996-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/c86f31a08efe/pharmaceutics-15-00996-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/2d4e7ecc19b2/pharmaceutics-15-00996-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/970ba9cf1064/pharmaceutics-15-00996-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/f09365d9654c/pharmaceutics-15-00996-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/0a64fcd4a5fd/pharmaceutics-15-00996-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/e2dd0cf35021/pharmaceutics-15-00996-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/2ca45a8d6a0e/pharmaceutics-15-00996-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/55c756b0872a/pharmaceutics-15-00996-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/650e7d8a6b08/pharmaceutics-15-00996-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/11b022f74360/pharmaceutics-15-00996-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/c86f31a08efe/pharmaceutics-15-00996-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/2d4e7ecc19b2/pharmaceutics-15-00996-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/970ba9cf1064/pharmaceutics-15-00996-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/f09365d9654c/pharmaceutics-15-00996-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/0a64fcd4a5fd/pharmaceutics-15-00996-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fed/10054254/e2dd0cf35021/pharmaceutics-15-00996-g010.jpg

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本文引用的文献

[1]
Cationically modified inhalable nintedanib niosomes: enhancing therapeutic activity against non-small-cell lung cancer.

Nanomedicine (Lond). 2022-6

[2]
Repurposing clofazimine for malignant pleural mesothelioma treatment - In-vitro assessment of efficacy and mechanism of action.

Life Sci. 2022-10-1

[3]
Development of gelatin methacrylate (GelMa) hydrogels for versatile intracavitary applications.

Biomater Sci. 2022-8-9

[4]
Simultaneous Spray Drying for Combination Dry Powder Inhaler Formulations.

Pharmaceutics. 2022-5-26

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An alternative method to enhance w/o emulsion stability using modified dimer acid and its application in oil based drilling fluids.

RSC Adv. 2018-7-23

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Biol Methods Protoc. 2022-1-27

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Sci Rep. 2021-9-15

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Local Treatment of Non-small Cell Lung Cancer with a Spray-Dried Bevacizumab Formulation.

AAPS PharmSciTech. 2021-8-31

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Chest. 2022-1

[10]
Impact of simulated lung fluid components on the solubility of inhaled drugs and predicted in vivo performance.

Int J Pharm. 2021-9-5

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