Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation

Xiao Hu,1 Feifei Yang,2 Yonghong Liao,2 Lin Li,1 Guoguang Zhao,3 Lan Zhang1 1Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, People’s Republ...

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Autores principales:	Hu X, Yang F, Liao Y, Li L, Zhao G, Zhang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	pulmonary delivery docetaxel lung cancer spray-drying dry powder. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7be1019f81624ca28dd02d46125a332d
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spelling	oai:doaj.org-article:7be1019f81624ca28dd02d46125a332d2021-12-02T10:15:09ZDocetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation1178-2013https://doaj.org/article/7be1019f81624ca28dd02d46125a332d2020-07-01T00:00:00Zhttps://www.dovepress.com/docetaxel-loaded-cholesterol-peg-co-modified-poly-n-butyl-cyanoacrylat-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiao Hu,1 Feifei Yang,2 Yonghong Liao,2 Lin Li,1 Guoguang Zhao,3 Lan Zhang1 1Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, People’s Republic of China; 2Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, People’s Republic of China; 3Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, People’s Republic of ChinaCorrespondence: Guoguang Zhao; Lan Zhang Email ggzhao@vip.sina.com; lanizhg@126.comBackground and Aim: Polymeric nanoparticles (NPs) have received much attention as promising carrier systems in lung cancer and brain metastases.Methods: Here, for the first time, we investigated the feasibility of using inhaled cholesterol-PEG co-modified poly (n-butyl) cyanoacrylate NPs (CLS-PEG NPs) of docetaxel (DTX) for sustained pulmonary drug delivery in cancer metastasis.Results: Spray-dried or freeze-dried NPs yielded sustained drug release in vitro. In vitro inhalation evaluation data indicated that the inhalation formulation had better inhalability. Compared with intravenous (IV) administration, pharmacokinetic data suggested that the inhalation formulation prolonged plasma concentration of DTX for greater than 24 h and is more quickly and completely absorbed into the rat lung after intratracheal (IT) administration. Furthermore, freeze-dried powders were found to increase the t1/2 and area under curve (AUC) by 2.3 and 6.5 fold compared to the free drug after IT administration, and spray-dried powders were found to increase the t1/2 and AUC by 3.4 and 8.8 fold, respectively. After pulmonary administration of the inhalation formulation, DTX appeared to prolong the pulmonary absorption time. In addition, the inhalation formulation was distributed to the brain in a sustained release manner.Conclusion: These experimental results demonstrated that freeze- and spray-dried powders have the potential for pulmonary sustained release, and they also have the potential to be used as a novel treatment for the delivery of drugs that pass through the air–blood barrier and enter the brain and are efficient carriers for the treatment of brain metastasis.Keywords: pulmonary delivery, docetaxel, lung cancer, spray-drying, dry powderHu XYang FLiao YLi LZhao GZhang LDove Medical Pressarticlepulmonary deliverydocetaxellung cancerspray-dryingdry powder.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 5361-5376 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	pulmonary delivery docetaxel lung cancer spray-drying dry powder. Medicine (General) R5-920
spellingShingle	pulmonary delivery docetaxel lung cancer spray-drying dry powder. Medicine (General) R5-920 Hu X Yang F Liao Y Li L Zhao G Zhang L Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation
description	Xiao Hu,1 Feifei Yang,2 Yonghong Liao,2 Lin Li,1 Guoguang Zhao,3 Lan Zhang1 1Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, People’s Republic of China; 2Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, People’s Republic of China; 3Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, People’s Republic of ChinaCorrespondence: Guoguang Zhao; Lan Zhang Email ggzhao@vip.sina.com; lanizhg@126.comBackground and Aim: Polymeric nanoparticles (NPs) have received much attention as promising carrier systems in lung cancer and brain metastases.Methods: Here, for the first time, we investigated the feasibility of using inhaled cholesterol-PEG co-modified poly (n-butyl) cyanoacrylate NPs (CLS-PEG NPs) of docetaxel (DTX) for sustained pulmonary drug delivery in cancer metastasis.Results: Spray-dried or freeze-dried NPs yielded sustained drug release in vitro. In vitro inhalation evaluation data indicated that the inhalation formulation had better inhalability. Compared with intravenous (IV) administration, pharmacokinetic data suggested that the inhalation formulation prolonged plasma concentration of DTX for greater than 24 h and is more quickly and completely absorbed into the rat lung after intratracheal (IT) administration. Furthermore, freeze-dried powders were found to increase the t1/2 and area under curve (AUC) by 2.3 and 6.5 fold compared to the free drug after IT administration, and spray-dried powders were found to increase the t1/2 and AUC by 3.4 and 8.8 fold, respectively. After pulmonary administration of the inhalation formulation, DTX appeared to prolong the pulmonary absorption time. In addition, the inhalation formulation was distributed to the brain in a sustained release manner.Conclusion: These experimental results demonstrated that freeze- and spray-dried powders have the potential for pulmonary sustained release, and they also have the potential to be used as a novel treatment for the delivery of drugs that pass through the air–blood barrier and enter the brain and are efficient carriers for the treatment of brain metastasis.Keywords: pulmonary delivery, docetaxel, lung cancer, spray-drying, dry powder
format	article
author	Hu X Yang F Liao Y Li L Zhao G Zhang L
author_facet	Hu X Yang F Liao Y Li L Zhao G Zhang L
author_sort	Hu X
title	Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation
title_short	Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation
title_full	Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation
title_fullStr	Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation
title_full_unstemmed	Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation
title_sort	docetaxel-loaded cholesterol-peg co-modified poly (n-butyl) cyanoacrylate nanoparticles for antitumor drug pulmonary delivery: preparation, characterization, and in vivo evaluation
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/7be1019f81624ca28dd02d46125a332d
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Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation

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