Nanoemulsion loaded with lycobetaine–oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity

Hui Zhao, Hua Lu, Tao Gong, Zhirong ZhangKey Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, People's Republic of ChinaBackground: Intravenous injection of lycobetaine was found to show significant cytotoxic activity against (inter alia) Lewis lung carcinoma...

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Autores principales: Zhao H, Lu H, Gong T, Zhang ZR
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Publicado: Dove Medical Press 2013
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spelling oai:doaj.org-article:bc32267b1d604604977e47af113118c32021-12-02T05:09:48ZNanoemulsion loaded with lycobetaine&ndash;oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity1176-91141178-2013https://doaj.org/article/bc32267b1d604604977e47af113118c32013-05-01T00:00:00Zhttp://www.dovepress.com/nanoemulsion-loaded-with-lycobetainendasholeic-acid-ionic-complex-phys-a13109https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Hui Zhao, Hua Lu, Tao Gong, Zhirong ZhangKey Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, People&#39;s Republic of ChinaBackground: Intravenous injection of lycobetaine was found to show significant cytotoxic activity against (inter alia) Lewis lung carcinoma, but its therapeutic use is largely limited due to an extremely short half-life in blood. This study aimed at developing a novel lipid nanocarrier-based formulation for lycobetaine delivery. The formulation is feasible for scale-up production, exhibiting good parenteral acceptability and improved circulation characteristics.Methods: To enhance its lipophilicity, oleic acid was selected to form ionic complexes with lycobetaine (LBT). The nanoemulsion loaded with LBT&ndash;oleic acid complex (LBT&ndash;OA&ndash;nanoemulsion) and PEGylated LBT&ndash;OA&ndash;nanoemulsion (NE) (LBT&ndash;OA&ndash;PEG&ndash;NE) were prepared by a simple high-pressure homogenization method.Results: A high-encapsulation efficiency of around 97.32% &plusmn; 2.09% was obtained for LBT&ndash;OA&ndash;PEG&ndash;NE under optimized conditions. Furthermore, the in vivo pharmacokinetics and biodistribution of LBT&ndash;OA&ndash;NE, LBT&ndash;OA&ndash;PEG&ndash;NE, and free LBT were studied in rats. Free LBT and LBT&ndash;OA&ndash;PEG&ndash;NE displayed AUC0&ndash;10h (area under the concentration-time curve from 0 to 10 hours) of 112.99 mg/L*minute and 3452.09 mg/L*minute via intravenous administration (P < 0.005), respectively. Moreover, LBT&ndash;OA&ndash;PEG&ndash;NE showed significantly lower LBT concentration in the heart, liver, and kidney, while achieving higher concentration of LBT in the lung when compared to free LBT at the same time (P < 0.005). The LBT&ndash;OA&ndash;PEG&ndash;NE exhibited higher growth inhibitory effect and longer survival time than free LBT in both heterotopic and lung metastatic tumor models.Conclusion: These results demonstrated that LBT&ndash;OA&ndash;PEG&ndash;NE is an attractive parenteral formulation for cancer therapy.Keywords: lycobetaine, oleic acid, polyethylene glycol, nanoemulsion, in vivo studies, antitumor activityZhao HLu HGong TZhang ZRDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1959-1973 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Zhao H
Lu H
Gong T
Zhang ZR
Nanoemulsion loaded with lycobetaine&ndash;oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity
description Hui Zhao, Hua Lu, Tao Gong, Zhirong ZhangKey Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, People&#39;s Republic of ChinaBackground: Intravenous injection of lycobetaine was found to show significant cytotoxic activity against (inter alia) Lewis lung carcinoma, but its therapeutic use is largely limited due to an extremely short half-life in blood. This study aimed at developing a novel lipid nanocarrier-based formulation for lycobetaine delivery. The formulation is feasible for scale-up production, exhibiting good parenteral acceptability and improved circulation characteristics.Methods: To enhance its lipophilicity, oleic acid was selected to form ionic complexes with lycobetaine (LBT). The nanoemulsion loaded with LBT&ndash;oleic acid complex (LBT&ndash;OA&ndash;nanoemulsion) and PEGylated LBT&ndash;OA&ndash;nanoemulsion (NE) (LBT&ndash;OA&ndash;PEG&ndash;NE) were prepared by a simple high-pressure homogenization method.Results: A high-encapsulation efficiency of around 97.32% &plusmn; 2.09% was obtained for LBT&ndash;OA&ndash;PEG&ndash;NE under optimized conditions. Furthermore, the in vivo pharmacokinetics and biodistribution of LBT&ndash;OA&ndash;NE, LBT&ndash;OA&ndash;PEG&ndash;NE, and free LBT were studied in rats. Free LBT and LBT&ndash;OA&ndash;PEG&ndash;NE displayed AUC0&ndash;10h (area under the concentration-time curve from 0 to 10 hours) of 112.99 mg/L*minute and 3452.09 mg/L*minute via intravenous administration (P < 0.005), respectively. Moreover, LBT&ndash;OA&ndash;PEG&ndash;NE showed significantly lower LBT concentration in the heart, liver, and kidney, while achieving higher concentration of LBT in the lung when compared to free LBT at the same time (P < 0.005). The LBT&ndash;OA&ndash;PEG&ndash;NE exhibited higher growth inhibitory effect and longer survival time than free LBT in both heterotopic and lung metastatic tumor models.Conclusion: These results demonstrated that LBT&ndash;OA&ndash;PEG&ndash;NE is an attractive parenteral formulation for cancer therapy.Keywords: lycobetaine, oleic acid, polyethylene glycol, nanoemulsion, in vivo studies, antitumor activity
format article
author Zhao H
Lu H
Gong T
Zhang ZR
author_facet Zhao H
Lu H
Gong T
Zhang ZR
author_sort Zhao H
title Nanoemulsion loaded with lycobetaine&ndash;oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity
title_short Nanoemulsion loaded with lycobetaine&ndash;oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity
title_full Nanoemulsion loaded with lycobetaine&ndash;oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity
title_fullStr Nanoemulsion loaded with lycobetaine&ndash;oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity
title_full_unstemmed Nanoemulsion loaded with lycobetaine&ndash;oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity
title_sort nanoemulsion loaded with lycobetaine&ndash;oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/bc32267b1d604604977e47af113118c3
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