Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles

Xue Yuan,1,2 Qian Xie,1 Keyu Su,1 Zhijie Li,3 Dong Dong,3 Baojian Wu1,2 1Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, 2Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, 3International Ocular Surface Research Centre an...

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Autores principales:	Yuan X, Xie Q, Su K, Li Z, Dong D, Wu B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Bufanolide steroid Arenobufagin Nanomicelles mPEG-PLGA Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/809d3f756707481f88639cc5d88ebc06
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spelling	oai:doaj.org-article:809d3f756707481f88639cc5d88ebc062021-12-02T05:00:27ZSystemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles1178-2013https://doaj.org/article/809d3f756707481f88639cc5d88ebc062017-07-01T00:00:00Zhttps://www.dovepress.com/systemic-delivery-of-the-anticancer-agent-arenobufagin-using-polymeric-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xue Yuan,1,2 Qian Xie,1 Keyu Su,1 Zhijie Li,3 Dong Dong,3 Baojian Wu1,2 1Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, 2Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, 3International Ocular Surface Research Centre and Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China Abstract: Arenobufagin (ABG) is a major active component of toad venom, a traditional Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its pharmacological studies in vivo due to administration difficulties. In this study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene glycol)-block-poly (D,L-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique. The obtained ABG-PNs were 105 nm in size with a small polydispersity index of 0.08. The entrapment efficiency and drug loading were 71.9% and 4.58%, respectively. Cellular uptake of ABG-PNs was controlled by specific clathrin-mediated endocytosis. In addition, ABG-PNs showed improved drug pharmacokinetics with an increased area under the curve value (a 1.73-fold increase) and a decreased elimination clearance (37.8% decrease). The nanomicelles showed increased drug concentrations in the liver and lung. In contrast, drug concentrations in both heart and brain were decreased. Moreover, the nanomicelles enhanced the anticancer effect of the pure drug probably via increased cellular uptake of drug molecules. In conclusion, the mPEG-PLGA-based nanomicelle system is a satisfactory carrier for the systemic delivery of ABG. Keywords: bufanolide steroid, arenobufagin, nanomicelles, mPEG-PLGAYuan XXie QSu KLi ZDong DWu BDove Medical PressarticleBufanolide steroidArenobufaginNanomicellesmPEG-PLGAMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4981-4989 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bufanolide steroid Arenobufagin Nanomicelles mPEG-PLGA Medicine (General) R5-920
spellingShingle	Bufanolide steroid Arenobufagin Nanomicelles mPEG-PLGA Medicine (General) R5-920 Yuan X Xie Q Su K Li Z Dong D Wu B Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles
description	Xue Yuan,1,2 Qian Xie,1 Keyu Su,1 Zhijie Li,3 Dong Dong,3 Baojian Wu1,2 1Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, 2Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, 3International Ocular Surface Research Centre and Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China Abstract: Arenobufagin (ABG) is a major active component of toad venom, a traditional Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its pharmacological studies in vivo due to administration difficulties. In this study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene glycol)-block-poly (D,L-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique. The obtained ABG-PNs were 105 nm in size with a small polydispersity index of 0.08. The entrapment efficiency and drug loading were 71.9% and 4.58%, respectively. Cellular uptake of ABG-PNs was controlled by specific clathrin-mediated endocytosis. In addition, ABG-PNs showed improved drug pharmacokinetics with an increased area under the curve value (a 1.73-fold increase) and a decreased elimination clearance (37.8% decrease). The nanomicelles showed increased drug concentrations in the liver and lung. In contrast, drug concentrations in both heart and brain were decreased. Moreover, the nanomicelles enhanced the anticancer effect of the pure drug probably via increased cellular uptake of drug molecules. In conclusion, the mPEG-PLGA-based nanomicelle system is a satisfactory carrier for the systemic delivery of ABG. Keywords: bufanolide steroid, arenobufagin, nanomicelles, mPEG-PLGA
format	article
author	Yuan X Xie Q Su K Li Z Dong D Wu B
author_facet	Yuan X Xie Q Su K Li Z Dong D Wu B
author_sort	Yuan X
title	Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles
title_short	Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles
title_full	Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles
title_fullStr	Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles
title_full_unstemmed	Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles
title_sort	systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/809d3f756707481f88639cc5d88ebc06
work_keys_str_mv	AT yuanx systemicdeliveryoftheanticanceragentarenobufaginusingpolymericnanomicelles AT xieq systemicdeliveryoftheanticanceragentarenobufaginusingpolymericnanomicelles AT suk systemicdeliveryoftheanticanceragentarenobufaginusingpolymericnanomicelles AT liz systemicdeliveryoftheanticanceragentarenobufaginusingpolymericnanomicelles AT dongd systemicdeliveryoftheanticanceragentarenobufaginusingpolymericnanomicelles AT wub systemicdeliveryoftheanticanceragentarenobufaginusingpolymericnanomicelles
_version_	1718400839271317504

Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles

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