Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes

Jing Qin,1 Xu Yang,1–3 Jia Mi,4 Jianxin Wang,1 Jia Hou,1,2 Teng Shen,1 Yongji Li,2 Bin Wang,4 Xuri Li,4 Weili Zhu5 1Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 2Department of Pharmaceu...

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Autores principales:	Qin J, Yang X, Mi J, Wang J, Hou J, Shen T, Li Y, Wang B, Li X, Zhu W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0ef984c339e44882a8a398a1ca568e61
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spelling	oai:doaj.org-article:0ef984c339e44882a8a398a1ca568e612021-12-02T02:21:18ZEnhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes1178-2013https://doaj.org/article/0ef984c339e44882a8a398a1ca568e612014-11-01T00:00:00Zhttp://www.dovepress.com/enhanced-antidepressant-like-effects-of-the-macromolecule-trefoil-fact-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Jing Qin,1 Xu Yang,1–3 Jia Mi,4 Jianxin Wang,1 Jia Hou,1,2 Teng Shen,1 Yongji Li,2 Bin Wang,4 Xuri Li,4 Weili Zhu5 1Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 2Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 3Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 4Binzhou Medical University, Yantai, 5National Institute on Drug Dependence, Peking University, Beijing, People’s Republic of China Abstract: Immunocytes, mainly neutrophils and monocytes, exhibit an intrinsic homing property, enabling them to migrate to sites of injury and inflammation. They can thus act as Trojan horses carrying concealed drug cargoes while migrating across impermeable barriers to sites of disease, especially the blood–brain barrier (BBB). In this study, to target circulating phagocytic cells, we formulated negatively charged nanosize liposomes and loaded trefoil factor 3 (TFF3) into liposomes by the pH-gradient method. According to the optimized formulation (5:1.5 of lipid to cholesterol, 10:1 of lipid to drug, 10 mg/mL of lipid concentration, and 10 mmol/L of phosphate-buffered saline), 44.47% entrapment efficiency was obtained for TFF3 liposomes with 129.6 nm particle size and –36.6 mV zeta potential. Compared with neutrally charged liposomes, the negatively charged liposomes showed a strong binding capacity with monocytes and were effectively carried by monocytes to cross the BBB in vitro. Furthermore, enhanced antidepressant-like effects were found in the tail-suspension and forced-swim tests in mice, as measured by decreased immobility time, as well as increased swimming time and reduced immobility in rats. These results suggested that negatively charged liposomes could improve the behavioral responses of TFF3, and our study opens up a new way for the development of effective therapies for brain disease by increasing the permeability of the BBB. Keywords: TFF3, drug delivery system, monocytes, brain-targeting drug delivery, antidepressant, blood–brain barrierQin JYang XMi JWang JHou JShen TLi YWang BLi XZhu WDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5247-5257 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Qin J Yang X Mi J Wang J Hou J Shen T Li Y Wang B Li X Zhu W Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes
description	Jing Qin,1 Xu Yang,1–3 Jia Mi,4 Jianxin Wang,1 Jia Hou,1,2 Teng Shen,1 Yongji Li,2 Bin Wang,4 Xuri Li,4 Weili Zhu5 1Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 2Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 3Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 4Binzhou Medical University, Yantai, 5National Institute on Drug Dependence, Peking University, Beijing, People’s Republic of China Abstract: Immunocytes, mainly neutrophils and monocytes, exhibit an intrinsic homing property, enabling them to migrate to sites of injury and inflammation. They can thus act as Trojan horses carrying concealed drug cargoes while migrating across impermeable barriers to sites of disease, especially the blood–brain barrier (BBB). In this study, to target circulating phagocytic cells, we formulated negatively charged nanosize liposomes and loaded trefoil factor 3 (TFF3) into liposomes by the pH-gradient method. According to the optimized formulation (5:1.5 of lipid to cholesterol, 10:1 of lipid to drug, 10 mg/mL of lipid concentration, and 10 mmol/L of phosphate-buffered saline), 44.47% entrapment efficiency was obtained for TFF3 liposomes with 129.6 nm particle size and –36.6 mV zeta potential. Compared with neutrally charged liposomes, the negatively charged liposomes showed a strong binding capacity with monocytes and were effectively carried by monocytes to cross the BBB in vitro. Furthermore, enhanced antidepressant-like effects were found in the tail-suspension and forced-swim tests in mice, as measured by decreased immobility time, as well as increased swimming time and reduced immobility in rats. These results suggested that negatively charged liposomes could improve the behavioral responses of TFF3, and our study opens up a new way for the development of effective therapies for brain disease by increasing the permeability of the BBB. Keywords: TFF3, drug delivery system, monocytes, brain-targeting drug delivery, antidepressant, blood–brain barrier
format	article
author	Qin J Yang X Mi J Wang J Hou J Shen T Li Y Wang B Li X Zhu W
author_facet	Qin J Yang X Mi J Wang J Hou J Shen T Li Y Wang B Li X Zhu W
author_sort	Qin J
title	Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes
title_short	Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes
title_full	Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes
title_fullStr	Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes
title_full_unstemmed	Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes
title_sort	enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/0ef984c339e44882a8a398a1ca568e61
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Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes

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