Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery

Kang Liu,1 Weijuan Chen,2 Tingting Yang,1 Baofang Wen,1 Dejun Ding,1 Michael Keidar,3 Jinbao Tang,1 Weifen Zhang1 1College of Pharmacy, Weifang Medical University, Weifang, 2Department of Pathology, People’s Hospital of Shouguang, Shouguang, People’s Republic of China; 3Departme...

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Autores principales:	Liu K, Chen W, Yang T, Wen B, Ding D, Keidar M, Tang J, Zhang W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Paclitaxel Quercetin Oleic acid Chitosan Nanoparticles Polymerization microspheres Pulmonary delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fb7828759d4446509cd666e2a00b3d58
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spelling	oai:doaj.org-article:fb7828759d4446509cd666e2a00b3d582021-12-02T02:42:31ZPaclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery1178-2013https://doaj.org/article/fb7828759d4446509cd666e2a00b3d582017-11-01T00:00:00Zhttps://www.dovepress.com/paclitaxel-and-quercetin-nanoparticles-co-loaded-in-microspheres-to-pr-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kang Liu,1 Weijuan Chen,2 Tingting Yang,1 Baofang Wen,1 Dejun Ding,1 Michael Keidar,3 Jinbao Tang,1 Weifen Zhang1 1College of Pharmacy, Weifang Medical University, Weifang, 2Department of Pathology, People’s Hospital of Shouguang, Shouguang, People’s Republic of China; 3Department of Mechanical and Aerospace Engineering, School of Engineering and Applied Science, The George Washington University, Washington, DC, USA Abstract: High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery. We report the development of novel NPs in the form of PMs loaded with paclitaxel (PTX) and quercetin (QUE) double drugs based on the synthesis of oleic acid-conjugated chitosan (OA-CTS) for pulmonary delivery. This approach is aimed toward prolonging PTX retention time in the presence of QUE and bypassing P-glycoprotein drug efflux pumps. NPs loaded with PTX or QUE were prepared with 11% substitution degree using OA-CTS as the carrier by ionic cross-linking method, which NPs loaded with PTX or QUE were used in the preparation of PMs by spray-drying. The diameters of the PMs ranged from 1 to 5 µm which had uniform size range. Scanning electron microscopy showed that PMs were polymers formed by a large number of NPs and readily redispersed (after redispersion, size of NPs ranged between 250 and 350 nm) in water within 1 h. PMs displayed slow-release characteristics at pH 4.5 and 7.4. The in vivo pharmacokinetic and biodistribution studies suggested that PMs exhibit prolonged circulation time and a markedly high accumulation in the lung. The obtained results indicate that PMs can serve as a promising pulmonary delivery system for combined pharmacotherapy using hydrophobic anticancer drugs. Keywords: paclitaxel, quercetin, oleic acid-conjugated chitosan, nanoparticles, polymeric microspheres, pulmonary delivery Liu KChen WYang TWen BDing DKeidar MTang JZhang WDove Medical PressarticlePaclitaxelQuercetinOleic acid ChitosanNanoparticlesPolymerization microspheresPulmonary deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8239-8255 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Paclitaxel Quercetin Oleic acid Chitosan Nanoparticles Polymerization microspheres Pulmonary delivery Medicine (General) R5-920
spellingShingle	Paclitaxel Quercetin Oleic acid Chitosan Nanoparticles Polymerization microspheres Pulmonary delivery Medicine (General) R5-920 Liu K Chen W Yang T Wen B Ding D Keidar M Tang J Zhang W Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery
description	Kang Liu,1 Weijuan Chen,2 Tingting Yang,1 Baofang Wen,1 Dejun Ding,1 Michael Keidar,3 Jinbao Tang,1 Weifen Zhang1 1College of Pharmacy, Weifang Medical University, Weifang, 2Department of Pathology, People’s Hospital of Shouguang, Shouguang, People’s Republic of China; 3Department of Mechanical and Aerospace Engineering, School of Engineering and Applied Science, The George Washington University, Washington, DC, USA Abstract: High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery. We report the development of novel NPs in the form of PMs loaded with paclitaxel (PTX) and quercetin (QUE) double drugs based on the synthesis of oleic acid-conjugated chitosan (OA-CTS) for pulmonary delivery. This approach is aimed toward prolonging PTX retention time in the presence of QUE and bypassing P-glycoprotein drug efflux pumps. NPs loaded with PTX or QUE were prepared with 11% substitution degree using OA-CTS as the carrier by ionic cross-linking method, which NPs loaded with PTX or QUE were used in the preparation of PMs by spray-drying. The diameters of the PMs ranged from 1 to 5 µm which had uniform size range. Scanning electron microscopy showed that PMs were polymers formed by a large number of NPs and readily redispersed (after redispersion, size of NPs ranged between 250 and 350 nm) in water within 1 h. PMs displayed slow-release characteristics at pH 4.5 and 7.4. The in vivo pharmacokinetic and biodistribution studies suggested that PMs exhibit prolonged circulation time and a markedly high accumulation in the lung. The obtained results indicate that PMs can serve as a promising pulmonary delivery system for combined pharmacotherapy using hydrophobic anticancer drugs. Keywords: paclitaxel, quercetin, oleic acid-conjugated chitosan, nanoparticles, polymeric microspheres, pulmonary delivery
format	article
author	Liu K Chen W Yang T Wen B Ding D Keidar M Tang J Zhang W
author_facet	Liu K Chen W Yang T Wen B Ding D Keidar M Tang J Zhang W
author_sort	Liu K
title	Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery
title_short	Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery
title_full	Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery
title_fullStr	Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery
title_full_unstemmed	Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery
title_sort	paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/fb7828759d4446509cd666e2a00b3d58
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Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery

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