Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies

Xiaofei Wang,1,2 Qinyue Chen,1 Xiaoyan Zhang,1 Xiaoqing Ren,1 Xiulei Zhang,1 Lin Meng,1 Huihui Liang,1 Xianyi Sha,1 Xiaoling Fang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education of China, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 2Shanghai&...

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Autores principales:	Wang X, Chen Q, Zhang X, Ren X, Meng L, Liang H, Sha X, Fang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	matrix metalloproteinases inhalation Pluronic paclitaxel P-glycoprotein Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/45193ec9e9e6430b9d60b54f5e311859
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spelling	oai:doaj.org-article:45193ec9e9e6430b9d60b54f5e3118592021-12-02T00:01:18ZMatrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies1178-2013https://doaj.org/article/45193ec9e9e6430b9d60b54f5e3118592018-08-01T00:00:00Zhttps://www.dovepress.com/matrix-metalloproteinase-29-triggered-release-micelles-for-inhaled-dru-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaofei Wang,1,2 Qinyue Chen,1 Xiaoyan Zhang,1 Xiaoqing Ren,1 Xiulei Zhang,1 Lin Meng,1 Huihui Liang,1 Xianyi Sha,1 Xiaoling Fang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education of China, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Omni Pharmaceuticall Co., Ltd., Shanghai, People’s Republic of China Background: Improvement in drug accumulation in the lungs through inhalation administration and high expression of MMP2 and MMP9 in lung tumors have both been widely reported. Methods: MMP2/9-triggered-release micelles were constructed and in vitro and in vivo studies of inhalation administration against lung tumor carried out. Pluronic P123 (P123) was modified with GPLGIAGQ-NH2 (GQ8) peptide to obtain P123-GQ8 (PG). MMP2/9-triggered-release micelles were constructed using PG and succinylated gelatin (SG) and loading paclitaxel (Ptx). To study biodistribution of micelles, DiR encapsulated in micelles was dosed to rats via intravenous injection or inhalation before ex vivo imaging for detecting DiR quantity in lungs. And B16F10 lung cancer-bearing nude mice were chosen as animal models to evaluate in vivo efficacy of MMP2/9-triggered-release micelles. Results: Ptx-release efficiency from PG-SG-Ptx micelles was MMP2/9-concentration-dependent. For A549 cells, PG-SG-Ptx cytotoxicity was significantly greater (P<0.001) compared to P123-Ptx. Aerosol inhalation was chosen as the method of administration. In biodistribution experiment, DiR quantity in lungs was 5.8%±0.4% of that in major organs, while the ratio was 38.8%±0.5% for inhalation. For B16F10 lung cancer-bearing nude mice, the efficacy of inhalation of PG-SG-Ptx was significantly higher (P<0.001) than Taxol inhalation and injected PG-SG-Ptx. Inhaled PG-SG-Ptx also significantly inhibited the expression of Pgp in lung cancer. Conclusion: Inhalation of MMP2/9-triggered-release micelles increased tumor sensitivity to chemotherapeutics and reduced the toxicity of chemotherapy to healthy lung cells, which has great potential in lung cancer therapy. Keywords: matrix metalloproteinases, inhalation, Pluronic, paclitaxel, P-glycoproteinWang XChen QZhang XRen XZhang XMeng LLiang HSha XFang XDove Medical Pressarticlematrix metalloproteinasesinhalationPluronicpaclitaxelP-glycoproteinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4641-4659 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	matrix metalloproteinases inhalation Pluronic paclitaxel P-glycoprotein Medicine (General) R5-920
spellingShingle	matrix metalloproteinases inhalation Pluronic paclitaxel P-glycoprotein Medicine (General) R5-920 Wang X Chen Q Zhang X Ren X Zhang X Meng L Liang H Sha X Fang X Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies
description	Xiaofei Wang,1,2 Qinyue Chen,1 Xiaoyan Zhang,1 Xiaoqing Ren,1 Xiulei Zhang,1 Lin Meng,1 Huihui Liang,1 Xianyi Sha,1 Xiaoling Fang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education of China, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Omni Pharmaceuticall Co., Ltd., Shanghai, People’s Republic of China Background: Improvement in drug accumulation in the lungs through inhalation administration and high expression of MMP2 and MMP9 in lung tumors have both been widely reported. Methods: MMP2/9-triggered-release micelles were constructed and in vitro and in vivo studies of inhalation administration against lung tumor carried out. Pluronic P123 (P123) was modified with GPLGIAGQ-NH2 (GQ8) peptide to obtain P123-GQ8 (PG). MMP2/9-triggered-release micelles were constructed using PG and succinylated gelatin (SG) and loading paclitaxel (Ptx). To study biodistribution of micelles, DiR encapsulated in micelles was dosed to rats via intravenous injection or inhalation before ex vivo imaging for detecting DiR quantity in lungs. And B16F10 lung cancer-bearing nude mice were chosen as animal models to evaluate in vivo efficacy of MMP2/9-triggered-release micelles. Results: Ptx-release efficiency from PG-SG-Ptx micelles was MMP2/9-concentration-dependent. For A549 cells, PG-SG-Ptx cytotoxicity was significantly greater (P<0.001) compared to P123-Ptx. Aerosol inhalation was chosen as the method of administration. In biodistribution experiment, DiR quantity in lungs was 5.8%±0.4% of that in major organs, while the ratio was 38.8%±0.5% for inhalation. For B16F10 lung cancer-bearing nude mice, the efficacy of inhalation of PG-SG-Ptx was significantly higher (P<0.001) than Taxol inhalation and injected PG-SG-Ptx. Inhaled PG-SG-Ptx also significantly inhibited the expression of Pgp in lung cancer. Conclusion: Inhalation of MMP2/9-triggered-release micelles increased tumor sensitivity to chemotherapeutics and reduced the toxicity of chemotherapy to healthy lung cells, which has great potential in lung cancer therapy. Keywords: matrix metalloproteinases, inhalation, Pluronic, paclitaxel, P-glycoprotein
format	article
author	Wang X Chen Q Zhang X Ren X Zhang X Meng L Liang H Sha X Fang X
author_facet	Wang X Chen Q Zhang X Ren X Zhang X Meng L Liang H Sha X Fang X
author_sort	Wang X
title	Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies
title_short	Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies
title_full	Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies
title_fullStr	Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies
title_full_unstemmed	Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies
title_sort	matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/45193ec9e9e6430b9d60b54f5e311859
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Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies

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