10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy

Linjie Yang,1 Jingyi Hong,1 Jing Di,1 Yifei Guo,1 Meihua Han,1 Meifeng Liu,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, B...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yang L, Hong J, Di J, Guo Y, Han M, Liu M, Wang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	10-Hydroxycamptothecin Nanosuspensions stabilizer Antitumor efficacy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b96cedfa0ddd4398b5523d0b5c5913c4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b96cedfa0ddd4398b5523d0b5c5913c4
record_format	dspace
spelling	oai:doaj.org-article:b96cedfa0ddd4398b5523d0b5c5913c42021-12-02T08:07:44Z10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy1178-2013https://doaj.org/article/b96cedfa0ddd4398b5523d0b5c5913c42017-05-01T00:00:00Zhttps://www.dovepress.com/10-hydroxycamptothecin-hcpt-nanosuspensions-stabilized-by-mpeg1000-hcp-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Linjie Yang,1 Jingyi Hong,1 Jing Di,1 Yifei Guo,1 Meihua Han,1 Meifeng Liu,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: In this study, polyethylene glycol (PEG)ylated 10-hydroxycamptothecin (mPEG1000-HCPT) was synthesized and used as a stabilizer to prepare 10-hydroxycamptothecin (HCPT) nanosuspensions for their in vitro and in vivo antitumor investigation. The resultant HCPT nanosuspensions (HCPT-NSps) had a very high drug payload of 94.90% (w/w) and a mean particle size of 92.90±0.20 nm with narrow size distribution (polydispersity index of 0.16±0.01). HCPT-NSps could be lyophilized without the need of the addition of any cryoprotectant and then be reconstituted into nanosuspensions of a similar size by direct resuspension in water. HCPT was in crystalline form in HCPT-NSps. Using mPEG1000-HCPT as stabilizer, insoluble camptothecin and 7-ethyl-10-hydroxycamptothecin could also be easily made into nanosuspensions with similar features such as high drug payload, small particle size, and cryoprotectant-free freeze drying. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay indicated that the HCPT-NSps had a significantly higher cytotoxicity than HCPT injections, with 3.77 times lower IC50 value against HepG2 cells and 14.1 times lower IC50 value against MCF-7 cells. An in vivo study in H22 tumor-bearing mice after intravenous injection of HCPT-NSps demonstrated that HCPT-NSps significantly improved the antitumor efficacy compared to the commercially available HCPT injections (86.38% vs 34.97%) at the same dose of 5 mg/kg. Even at 1/4 of the dose, HCPT-NSps could also achieve a similar antitumor efficacy to that of HCPT injections. mPEG1000-HCPT may be a highly efficient stabilizer able to provide camptothecin-based drugs, and probably other antitumor agents containing aromatic structure, with unique nanosuspensions or nanocrystals for improved in vivo therapeutic efficacy. Keywords: 10-hydroxycamptothecin, nanosuspensions, stabilizer, antitumor efficacyYang LHong JDi JGuo YHan MLiu MWang XDove Medical Pressarticle10-HydroxycamptothecinNanosuspensionsstabilizerAntitumor efficacyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3681-3695 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	10-Hydroxycamptothecin Nanosuspensions stabilizer Antitumor efficacy Medicine (General) R5-920
spellingShingle	10-Hydroxycamptothecin Nanosuspensions stabilizer Antitumor efficacy Medicine (General) R5-920 Yang L Hong J Di J Guo Y Han M Liu M Wang X 10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy
description	Linjie Yang,1 Jingyi Hong,1 Jing Di,1 Yifei Guo,1 Meihua Han,1 Meifeng Liu,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: In this study, polyethylene glycol (PEG)ylated 10-hydroxycamptothecin (mPEG1000-HCPT) was synthesized and used as a stabilizer to prepare 10-hydroxycamptothecin (HCPT) nanosuspensions for their in vitro and in vivo antitumor investigation. The resultant HCPT nanosuspensions (HCPT-NSps) had a very high drug payload of 94.90% (w/w) and a mean particle size of 92.90±0.20 nm with narrow size distribution (polydispersity index of 0.16±0.01). HCPT-NSps could be lyophilized without the need of the addition of any cryoprotectant and then be reconstituted into nanosuspensions of a similar size by direct resuspension in water. HCPT was in crystalline form in HCPT-NSps. Using mPEG1000-HCPT as stabilizer, insoluble camptothecin and 7-ethyl-10-hydroxycamptothecin could also be easily made into nanosuspensions with similar features such as high drug payload, small particle size, and cryoprotectant-free freeze drying. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay indicated that the HCPT-NSps had a significantly higher cytotoxicity than HCPT injections, with 3.77 times lower IC50 value against HepG2 cells and 14.1 times lower IC50 value against MCF-7 cells. An in vivo study in H22 tumor-bearing mice after intravenous injection of HCPT-NSps demonstrated that HCPT-NSps significantly improved the antitumor efficacy compared to the commercially available HCPT injections (86.38% vs 34.97%) at the same dose of 5 mg/kg. Even at 1/4 of the dose, HCPT-NSps could also achieve a similar antitumor efficacy to that of HCPT injections. mPEG1000-HCPT may be a highly efficient stabilizer able to provide camptothecin-based drugs, and probably other antitumor agents containing aromatic structure, with unique nanosuspensions or nanocrystals for improved in vivo therapeutic efficacy. Keywords: 10-hydroxycamptothecin, nanosuspensions, stabilizer, antitumor efficacy
format	article
author	Yang L Hong J Di J Guo Y Han M Liu M Wang X
author_facet	Yang L Hong J Di J Guo Y Han M Liu M Wang X
author_sort	Yang L
title	10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy
title_short	10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy
title_full	10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy
title_fullStr	10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy
title_full_unstemmed	10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy
title_sort	10-hydroxycamptothecin (hcpt) nanosuspensions stabilized by mpeg1000-hcpt conjugate: high stabilizing efficiency and improved antitumor efficacy
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/b96cedfa0ddd4398b5523d0b5c5913c4
work_keys_str_mv	AT yangl 10hydroxycamptothecinhcptnanosuspensionsstabilizedbympeg1000hcptconjugatehighstabilizingefficiencyandimprovedantitumorefficacy AT hongj 10hydroxycamptothecinhcptnanosuspensionsstabilizedbympeg1000hcptconjugatehighstabilizingefficiencyandimprovedantitumorefficacy AT dij 10hydroxycamptothecinhcptnanosuspensionsstabilizedbympeg1000hcptconjugatehighstabilizingefficiencyandimprovedantitumorefficacy AT guoy 10hydroxycamptothecinhcptnanosuspensionsstabilizedbympeg1000hcptconjugatehighstabilizingefficiencyandimprovedantitumorefficacy AT hanm 10hydroxycamptothecinhcptnanosuspensionsstabilizedbympeg1000hcptconjugatehighstabilizingefficiencyandimprovedantitumorefficacy AT lium 10hydroxycamptothecinhcptnanosuspensionsstabilizedbympeg1000hcptconjugatehighstabilizingefficiencyandimprovedantitumorefficacy AT wangx 10hydroxycamptothecinhcptnanosuspensionsstabilizedbympeg1000hcptconjugatehighstabilizingefficiencyandimprovedantitumorefficacy
_version_	1718398683191443456

10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy

Ejemplares similares