Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy

Yanhua Jiang,1 Yongjian Zhou,1 Can Yang Zhang,2 Te Fang1 1Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Singapore-MIT Alliance for Research and Technology, Singapore 138602, SingaporeCorrespondence: Te Fan...

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Autores principales:	Jiang Y, Zhou Y, Zhang CY, Fang T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	ph-responsive polyprodrug micelles co-delivery controlled release cancer therapy. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/33b5544d76e0465fb891373ea40b6184
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spelling	oai:doaj.org-article:33b5544d76e0465fb891373ea40b61842021-12-02T11:27:25ZCo-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy1178-2013https://doaj.org/article/33b5544d76e0465fb891373ea40b61842020-05-01T00:00:00Zhttps://www.dovepress.com/co-delivery-of-paclitaxel-and-doxorubicin-by-ph-responsive-prodrug-mic-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yanhua Jiang,1 Yongjian Zhou,1 Can Yang Zhang,2 Te Fang1 1Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Singapore-MIT Alliance for Research and Technology, Singapore 138602, SingaporeCorrespondence: Te Fang Email tfang@cmu.edu.cnBackground: It is of great significance to develop intelligent co-delivery systems for cancer chemotherapy with improved therapeutic efficacy and few side-effects.Materials and Methods: Here, we reported a co-delivery system based on pH-sensitive polyprodrug micelles for simultaneous delivery of doxorubicin (DOX) and paclitaxel (PTX) as a combination chemotherapy with pH-triggered drug release profiles. The physicochemical properties, drug release profiles and mechanism, and cytotoxicity of PTX/DOX-PMs have been thoroughly investigated.Results and Discussion: The pH-sensitive polyprodrug was used as nanocarrier, and PTX was encapsulated into the micelles with high drug-loading content (25.6%). The critical micelle concentration (CMC) was about 3.16 mg/L, indicating the system could form the micelles at low concentration. The particle size of PTX/DOX-PMs was 110.5 nm, and increased to approximately 140 nm after incubation for 5 days which showed that the PTX/DOX-PMs had high serum stability. With decrease in pH value, the particle size first increased, and thenwas no longer detectable. Similar change trend was observed for CMC values. The zetapotential increased sharply with decrease in pH. These results demonstrated the pHsensitivity of PTX/DOX-PMs. In vitro drug release experiments and study on release mechanism showed that the drug release rate and accumulative release for PTX and DOX were dependent on the pH, showing the pH-triggered drug release profiles. Cytotoxicity assay displayed that the block copolymer showed negligible cytotoxicity, while the PTX/DOX-PMs possessed high cytotoxic effect against several tumor cell lines compared with free drugs and control.Conclusion: All the results demonstrated that the co-delivery system based on pH-sensitive polyprodrug could be a potent nanomedicine for combination cancer chemotherapy. In addition, construction based on polyprodrug and chemical drug could be a useful method to prepare multifunctional nanomedicine.Keywords: pH-responsive, polyprodrug micelles, co-delivery, controlled release, cancer therapyJiang YZhou YZhang CYFang TDove Medical Pressarticleph-responsivepolyprodrug micellesco-deliverycontrolled releasecancer therapy.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 3319-3331 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ph-responsive polyprodrug micelles co-delivery controlled release cancer therapy. Medicine (General) R5-920
spellingShingle	ph-responsive polyprodrug micelles co-delivery controlled release cancer therapy. Medicine (General) R5-920 Jiang Y Zhou Y Zhang CY Fang T Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy
description	Yanhua Jiang,1 Yongjian Zhou,1 Can Yang Zhang,2 Te Fang1 1Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Singapore-MIT Alliance for Research and Technology, Singapore 138602, SingaporeCorrespondence: Te Fang Email tfang@cmu.edu.cnBackground: It is of great significance to develop intelligent co-delivery systems for cancer chemotherapy with improved therapeutic efficacy and few side-effects.Materials and Methods: Here, we reported a co-delivery system based on pH-sensitive polyprodrug micelles for simultaneous delivery of doxorubicin (DOX) and paclitaxel (PTX) as a combination chemotherapy with pH-triggered drug release profiles. The physicochemical properties, drug release profiles and mechanism, and cytotoxicity of PTX/DOX-PMs have been thoroughly investigated.Results and Discussion: The pH-sensitive polyprodrug was used as nanocarrier, and PTX was encapsulated into the micelles with high drug-loading content (25.6%). The critical micelle concentration (CMC) was about 3.16 mg/L, indicating the system could form the micelles at low concentration. The particle size of PTX/DOX-PMs was 110.5 nm, and increased to approximately 140 nm after incubation for 5 days which showed that the PTX/DOX-PMs had high serum stability. With decrease in pH value, the particle size first increased, and thenwas no longer detectable. Similar change trend was observed for CMC values. The zetapotential increased sharply with decrease in pH. These results demonstrated the pHsensitivity of PTX/DOX-PMs. In vitro drug release experiments and study on release mechanism showed that the drug release rate and accumulative release for PTX and DOX were dependent on the pH, showing the pH-triggered drug release profiles. Cytotoxicity assay displayed that the block copolymer showed negligible cytotoxicity, while the PTX/DOX-PMs possessed high cytotoxic effect against several tumor cell lines compared with free drugs and control.Conclusion: All the results demonstrated that the co-delivery system based on pH-sensitive polyprodrug could be a potent nanomedicine for combination cancer chemotherapy. In addition, construction based on polyprodrug and chemical drug could be a useful method to prepare multifunctional nanomedicine.Keywords: pH-responsive, polyprodrug micelles, co-delivery, controlled release, cancer therapy
format	article
author	Jiang Y Zhou Y Zhang CY Fang T
author_facet	Jiang Y Zhou Y Zhang CY Fang T
author_sort	Jiang Y
title	Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy
title_short	Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy
title_full	Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy
title_fullStr	Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy
title_full_unstemmed	Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy
title_sort	co-delivery of paclitaxel and doxorubicin by ph-responsive prodrug micelles for cancer therapy
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/33b5544d76e0465fb891373ea40b6184
work_keys_str_mv	AT jiangy codeliveryofpaclitaxelanddoxorubicinbyphresponsiveprodrugmicellesforcancertherapy AT zhouy codeliveryofpaclitaxelanddoxorubicinbyphresponsiveprodrugmicellesforcancertherapy AT zhangcy codeliveryofpaclitaxelanddoxorubicinbyphresponsiveprodrugmicellesforcancertherapy AT fangt codeliveryofpaclitaxelanddoxorubicinbyphresponsiveprodrugmicellesforcancertherapy
_version_	1718395931114602496

Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy

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