Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification

Chun-Han Chen,1,2,* Tse-Hung Huang,3–5,* Ahmed O Elzoghby,6,7 Pei-Wen Wang,8 Chia-Wen Chang,9 Jia-You Fang9–12 1Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang...

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Autores principales:	Chen CH, Huang TH, Elzoghby AO, Wang PW, Chang CW, Fang JY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	squarticles squalene amitriptyline overdose antidote pharmacokinetics Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fa978309a29f484594f74c904adf2783
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spelling	oai:doaj.org-article:fa978309a29f484594f74c904adf27832021-12-02T02:42:32ZSquarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification1178-2013https://doaj.org/article/fa978309a29f484594f74c904adf27832017-11-01T00:00:00Zhttps://www.dovepress.com/squarticles-as-the-nanoantidotes-to-sequester-the-overdosed-antidepres-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chun-Han Chen,1,2,* Tse-Hung Huang,3–5,* Ahmed O Elzoghby,6,7 Pei-Wen Wang,8 Chia-Wen Chang,9 Jia-You Fang9–12 1Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, 3Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, 4School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 5School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 6Cancer Nanotechnology Research Laboratory (CNRL), 7Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 8Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 9Pharmaceutics Laboratory, Graduate Institute of Natural Products, 10Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, 11Department of Anesthesiology, Chang Gung Memorial Hospital, 12Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan *These authors contributed equally to this work Abstract: The increasing death rate caused by drug overdose points to an urgent demand for the development of novel detoxification therapy. In an attempt to detoxify tricyclic antidepressant overdose, we prepared a lipid nanoemulsion, called squarticles, as the nanoantidote. Squalene was the major lipid matrix of the squarticles. Here, we present the animal study to investigate both the pharmacokinetic and pharmacodynamic effects of squarticles on amitriptyline intoxication. The anionic and cationic squarticles had average diameters of 97 and 122 nm, respectively. Through the entrapment study, squarticles could intercept 40%–50% of the amitriptyline during 2 h with low leakage after loading into the nanoparticles. The results of isothermal titration calorimetry demonstrated greater interaction of amitriptyline with the surface of anionic squarticles (Ka =28,700) than with cationic ones (Ka =5,010). Real-time imaging showed that intravenous administration of anionic squarticles resulted in a prolonged retention in the circulation. In a rat model of amitriptyline poisoning, anionic squarticles increased the plasma drug concentration by 2.5-fold. The drug uptake in the highly perfused organs was diminished after squarticle infusion, indicating the lipid sink effect of bringing the entrapped overdosed drug in the tissues back into circulation. In addition, the anionic nanosystems restored the mean arterial pressure to near normal after amitriptyline injection. The survival rate of overdosed amitriptyline increased from 25% to 75% by treatment with squarticles. Our results show that the adverse effects of amitriptyline intoxication could be mitigated by administering anionic squarticles. This lipid nanoemulsion is a potent antidote to extract amitriptyline and eliminate it. Keywords: squarticles, squalene, amitriptyline, overdose, antidote, pharmacokineticsChen CHHuang THElzoghby AOWang PWChang CWFang JYDove Medical PressarticlesquarticlessqualeneamitriptylineoverdoseantidotepharmacokineticsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8071-8083 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	squarticles squalene amitriptyline overdose antidote pharmacokinetics Medicine (General) R5-920
spellingShingle	squarticles squalene amitriptyline overdose antidote pharmacokinetics Medicine (General) R5-920 Chen CH Huang TH Elzoghby AO Wang PW Chang CW Fang JY Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification
description	Chun-Han Chen,1,2,* Tse-Hung Huang,3–5,* Ahmed O Elzoghby,6,7 Pei-Wen Wang,8 Chia-Wen Chang,9 Jia-You Fang9–12 1Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, 3Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, 4School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 5School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 6Cancer Nanotechnology Research Laboratory (CNRL), 7Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 8Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 9Pharmaceutics Laboratory, Graduate Institute of Natural Products, 10Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, 11Department of Anesthesiology, Chang Gung Memorial Hospital, 12Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan *These authors contributed equally to this work Abstract: The increasing death rate caused by drug overdose points to an urgent demand for the development of novel detoxification therapy. In an attempt to detoxify tricyclic antidepressant overdose, we prepared a lipid nanoemulsion, called squarticles, as the nanoantidote. Squalene was the major lipid matrix of the squarticles. Here, we present the animal study to investigate both the pharmacokinetic and pharmacodynamic effects of squarticles on amitriptyline intoxication. The anionic and cationic squarticles had average diameters of 97 and 122 nm, respectively. Through the entrapment study, squarticles could intercept 40%–50% of the amitriptyline during 2 h with low leakage after loading into the nanoparticles. The results of isothermal titration calorimetry demonstrated greater interaction of amitriptyline with the surface of anionic squarticles (Ka =28,700) than with cationic ones (Ka =5,010). Real-time imaging showed that intravenous administration of anionic squarticles resulted in a prolonged retention in the circulation. In a rat model of amitriptyline poisoning, anionic squarticles increased the plasma drug concentration by 2.5-fold. The drug uptake in the highly perfused organs was diminished after squarticle infusion, indicating the lipid sink effect of bringing the entrapped overdosed drug in the tissues back into circulation. In addition, the anionic nanosystems restored the mean arterial pressure to near normal after amitriptyline injection. The survival rate of overdosed amitriptyline increased from 25% to 75% by treatment with squarticles. Our results show that the adverse effects of amitriptyline intoxication could be mitigated by administering anionic squarticles. This lipid nanoemulsion is a potent antidote to extract amitriptyline and eliminate it. Keywords: squarticles, squalene, amitriptyline, overdose, antidote, pharmacokinetics
format	article
author	Chen CH Huang TH Elzoghby AO Wang PW Chang CW Fang JY
author_facet	Chen CH Huang TH Elzoghby AO Wang PW Chang CW Fang JY
author_sort	Chen CH
title	Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification
title_short	Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification
title_full	Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification
title_fullStr	Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification
title_full_unstemmed	Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification
title_sort	squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/fa978309a29f484594f74c904adf2783
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Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification

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