Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy

Weiguang Li, Jianpeng Xue, Hanmei Xu State Key Laboratory of Natural Medicines, The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province, Department of Marine Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China Background: S-HM-3 is...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Li W, Xue J, Xu H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Paclitaxel S-HM-3 Combination therapy TPGS Solutol Anti-multidrug resistance Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/afb2875065204db6bed8ca5bcc858b23
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:afb2875065204db6bed8ca5bcc858b23
record_format	dspace
spelling	oai:doaj.org-article:afb2875065204db6bed8ca5bcc858b232021-12-02T01:14:19ZCombined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy1178-2013https://doaj.org/article/afb2875065204db6bed8ca5bcc858b232019-02-01T00:00:00Zhttps://www.dovepress.com/combined-administration-of-ptx-and-s-hm-3-in-tpgssolutol-micelle-syste-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Weiguang Li, Jianpeng Xue, Hanmei Xu State Key Laboratory of Natural Medicines, The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province, Department of Marine Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China Background: S-HM-3 is a tumor angiogenesis inhibitor with short half-life (25 min). In this present, TPGS/Solutol polymeric micelles was prepared to load together insoluble paclitaxel (PTX) and soluble S-HM-3, expecting to together deliver them to the tumor site with long-circulating, targeting function and combating multi-drug resistance (MDR). Materials and methods: PTX and S-HM-3 loaded TPGS/Solutol micelles (PHTSm) were prepared by the method of thin-film evaporation, and characterized by dynamic light scattering, transmission electron microscope (TEM), atomic force microscopy (AFM) and releasing properties. The anticancer effect of the polymeric micelles system was evaluated and confirmed by experiments of in vitro cell uptake study, in vivo pharmacokinetics, and pharmacodynamics studies. Results: Micelles exhibited smooth spherical morphology with 20~30 nm and low critical micelle concentration (CMC) value of 0.000124 mg/mL. Only about 30% of PTX were slowly released from micelles at 48h, which can beneficial to the long circulation in blood. The results of in vitro cell assay proved that S-HM-3 could be easier to get into MDA-MB-231 cell, and its angiogenesis inhibition ability was also enhanced after integrating into micelles. In particular, the results of in vivo studies showed that the half-life of S-HM-3 and PTX was significantly prolonged 25.27 and 5.54 folds, and their AUC0-∞ was enhanced 129.78 and 15.65 times, respectively. Meanwhile 83.05% tumor inhibition rate of PHTSm was achieved compared with 59.99% of PTX. Conclusions: TPGS and Solutol micelles hold promising potential to resolve the conundrum of combined therapy of cytotoxic drug and angiogenesis inhibitor with different physicochemical property and anticancer mechanism in clinical use. Keywords: paclitaxel, angiogenesis inhibitor, combination therapy, TPGS, Solutol, anti-multidrug resistanceLi WXue JXu HDove Medical PressarticlePaclitaxelS-HM-3Combination therapyTPGSSolutolAnti-multidrug resistanceMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1011-1026 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Paclitaxel S-HM-3 Combination therapy TPGS Solutol Anti-multidrug resistance Medicine (General) R5-920
spellingShingle	Paclitaxel S-HM-3 Combination therapy TPGS Solutol Anti-multidrug resistance Medicine (General) R5-920 Li W Xue J Xu H Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy
description	Weiguang Li, Jianpeng Xue, Hanmei Xu State Key Laboratory of Natural Medicines, The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province, Department of Marine Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China Background: S-HM-3 is a tumor angiogenesis inhibitor with short half-life (25 min). In this present, TPGS/Solutol polymeric micelles was prepared to load together insoluble paclitaxel (PTX) and soluble S-HM-3, expecting to together deliver them to the tumor site with long-circulating, targeting function and combating multi-drug resistance (MDR). Materials and methods: PTX and S-HM-3 loaded TPGS/Solutol micelles (PHTSm) were prepared by the method of thin-film evaporation, and characterized by dynamic light scattering, transmission electron microscope (TEM), atomic force microscopy (AFM) and releasing properties. The anticancer effect of the polymeric micelles system was evaluated and confirmed by experiments of in vitro cell uptake study, in vivo pharmacokinetics, and pharmacodynamics studies. Results: Micelles exhibited smooth spherical morphology with 20~30 nm and low critical micelle concentration (CMC) value of 0.000124 mg/mL. Only about 30% of PTX were slowly released from micelles at 48h, which can beneficial to the long circulation in blood. The results of in vitro cell assay proved that S-HM-3 could be easier to get into MDA-MB-231 cell, and its angiogenesis inhibition ability was also enhanced after integrating into micelles. In particular, the results of in vivo studies showed that the half-life of S-HM-3 and PTX was significantly prolonged 25.27 and 5.54 folds, and their AUC0-∞ was enhanced 129.78 and 15.65 times, respectively. Meanwhile 83.05% tumor inhibition rate of PHTSm was achieved compared with 59.99% of PTX. Conclusions: TPGS and Solutol micelles hold promising potential to resolve the conundrum of combined therapy of cytotoxic drug and angiogenesis inhibitor with different physicochemical property and anticancer mechanism in clinical use. Keywords: paclitaxel, angiogenesis inhibitor, combination therapy, TPGS, Solutol, anti-multidrug resistance
format	article
author	Li W Xue J Xu H
author_facet	Li W Xue J Xu H
author_sort	Li W
title	Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy
title_short	Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy
title_full	Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy
title_fullStr	Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy
title_full_unstemmed	Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy
title_sort	combined administration of ptx and s-hm-3 in tpgs/solutol micelle system for oncotarget therapy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/afb2875065204db6bed8ca5bcc858b23
work_keys_str_mv	AT liw combinedadministrationofptxandshm3intpgssolutolmicellesystemforoncotargettherapy AT xuej combinedadministrationofptxandshm3intpgssolutolmicellesystemforoncotargettherapy AT xuh combinedadministrationofptxandshm3intpgssolutolmicellesystemforoncotargettherapy
_version_	1718403219044958208

Combined administration of PTX and S-HM-3 in TPGS/Solutol micelle system for oncotarget therapy

Ejemplares similares