A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery

Conglian Yang,1 Tingting Wu,1 Yuting Qin,1 Yan Qi,1 Yu Sun,1 Miao Kong,1 Xue Jiang,1 Xianya Qin,1 Yaqi Shen,2 Zhiping Zhang1,3,4 1Tongji School of Pharmacy, 2Department of Radiology, Tongji Hospital, Tongji Medical College, 3National Engineering Research Center for Nanomedicine, 4Hubei Engineering...

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Autores principales:	Yang CL, Wu TT, Qin YT, Qi Y, Sun Y, Kong M, Jiang X, Qin XY, Shen YQ, Zhang ZP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	self-assembly doxorubicin drug delivery chemotherapy nanomedicine Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b3aabdf8e51542e2a8009c90af98d9af
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spelling	oai:doaj.org-article:b3aabdf8e51542e2a8009c90af98d9af2021-12-02T02:34:26ZA facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery1178-2013https://doaj.org/article/b3aabdf8e51542e2a8009c90af98d9af2018-03-01T00:00:00Zhttps://www.dovepress.com/a-facile-doxorubicin-dichloroacetate-conjugate-nanomedicine-with-high--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Conglian Yang,1 Tingting Wu,1 Yuting Qin,1 Yan Qi,1 Yu Sun,1 Miao Kong,1 Xue Jiang,1 Xianya Qin,1 Yaqi Shen,2 Zhiping Zhang1,3,4 1Tongji School of Pharmacy, 2Department of Radiology, Tongji Hospital, Tongji Medical College, 3National Engineering Research Center for Nanomedicine, 4Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Background: Doxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns. Methods: An amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor.Results: Doxorubicin-dichloroacetate conjugate can self-assemble into nanoparticles with small amount of DSPE-PEG2000, leading to high drug loading (71.8%, w/w) and diminished excipient associated concerns. The nanoparticles exhibited invisible systemic toxicity and high maximum tolerated dose of 75 mg DOX equiv./kg, which was 15-fold higher than that of free DOX. It also showed good tumor targeting capability and enhanced antitumor efficacy in murine melanoma model. Conclusion: This work provides a promising strategy to simplify the drug preparation process, increase drug loading content, reduce systemic toxicity as well as enhance antitumor efficiency. Keywords: self-assembly, doxorubicin, drug delivery, chemotherapy, nanomedicineYang CLWu TTQin YTQi YSun YKong MJiang XQin XYShen YQZhang ZPDove Medical Pressarticleself-assemblydoxorubicindrug deliverychemotherapynanomedicineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1281-1293 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	self-assembly doxorubicin drug delivery chemotherapy nanomedicine Medicine (General) R5-920
spellingShingle	self-assembly doxorubicin drug delivery chemotherapy nanomedicine Medicine (General) R5-920 Yang CL Wu TT Qin YT Qi Y Sun Y Kong M Jiang X Qin XY Shen YQ Zhang ZP A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery
description	Conglian Yang,1 Tingting Wu,1 Yuting Qin,1 Yan Qi,1 Yu Sun,1 Miao Kong,1 Xue Jiang,1 Xianya Qin,1 Yaqi Shen,2 Zhiping Zhang1,3,4 1Tongji School of Pharmacy, 2Department of Radiology, Tongji Hospital, Tongji Medical College, 3National Engineering Research Center for Nanomedicine, 4Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Background: Doxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns. Methods: An amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor.Results: Doxorubicin-dichloroacetate conjugate can self-assemble into nanoparticles with small amount of DSPE-PEG2000, leading to high drug loading (71.8%, w/w) and diminished excipient associated concerns. The nanoparticles exhibited invisible systemic toxicity and high maximum tolerated dose of 75 mg DOX equiv./kg, which was 15-fold higher than that of free DOX. It also showed good tumor targeting capability and enhanced antitumor efficacy in murine melanoma model. Conclusion: This work provides a promising strategy to simplify the drug preparation process, increase drug loading content, reduce systemic toxicity as well as enhance antitumor efficiency. Keywords: self-assembly, doxorubicin, drug delivery, chemotherapy, nanomedicine
format	article
author	Yang CL Wu TT Qin YT Qi Y Sun Y Kong M Jiang X Qin XY Shen YQ Zhang ZP
author_facet	Yang CL Wu TT Qin YT Qi Y Sun Y Kong M Jiang X Qin XY Shen YQ Zhang ZP
author_sort	Yang CL
title	A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery
title_short	A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery
title_full	A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery
title_fullStr	A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery
title_full_unstemmed	A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery
title_sort	facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/b3aabdf8e51542e2a8009c90af98d9af
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A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery

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