Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control

Yao An Shen,1,* Ing Luen Shyu,2,* Maggie Lu,3 Chun Lin He,4 Yen Mei Hsu,2 Hsiang Fa Liang,3 Chih Peng Liu,3 Ren Shyan Liu,5,6 Biing Jiun Shen,7 Yau Huei Wei,1 Chi Mu Chuang2,4 1Institute of Biochemistry and Molecular Biology, School of Life Sciences, 2Institute of Clinical Medicine, School of Medi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shen YA, Shyu IL, Lu M, He CL, Hsu YM, Liang HF, Liu CP, Liu RS, Shen BJ, Wei YH, Chuang CM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8d0c59114b61491db7f9bfa91ecbee87
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8d0c59114b61491db7f9bfa91ecbee87
record_format	dspace
spelling	oai:doaj.org-article:8d0c59114b61491db7f9bfa91ecbee872021-12-02T04:52:29ZBypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control1178-2013https://doaj.org/article/8d0c59114b61491db7f9bfa91ecbee872015-03-01T00:00:00Zhttp://www.dovepress.com/bypassing-the-epr-effect-with-a-nanomedicine-harboring-a-sustained-rel-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Yao An Shen,1,* Ing Luen Shyu,2,* Maggie Lu,3 Chun Lin He,4 Yen Mei Hsu,2 Hsiang Fa Liang,3 Chih Peng Liu,3 Ren Shyan Liu,5,6 Biing Jiun Shen,7 Yau Huei Wei,1 Chi Mu Chuang2,4 1Institute of Biochemistry and Molecular Biology, School of Life Sciences, 2Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, 3Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 4Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, 5Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 6National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, Taiwan; 7Division of Psychology, Nanyang Technological University, Singapore *These authors contributed equally to the work Abstract: The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil®, the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future. Keywords: enhanced permeability and retention effect, liposome, paclitaxel, ovarian cancer Shen YAShyu ILLu MHe CLHsu YMLiang HFLiu CPLiu RSShen BJWei YHChuang CMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2485-2502 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shen YA Shyu IL Lu M He CL Hsu YM Liang HF Liu CP Liu RS Shen BJ Wei YH Chuang CM Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control
description	Yao An Shen,1,* Ing Luen Shyu,2,* Maggie Lu,3 Chun Lin He,4 Yen Mei Hsu,2 Hsiang Fa Liang,3 Chih Peng Liu,3 Ren Shyan Liu,5,6 Biing Jiun Shen,7 Yau Huei Wei,1 Chi Mu Chuang2,4 1Institute of Biochemistry and Molecular Biology, School of Life Sciences, 2Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, 3Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 4Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, 5Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 6National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, Taiwan; 7Division of Psychology, Nanyang Technological University, Singapore *These authors contributed equally to the work Abstract: The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil®, the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future. Keywords: enhanced permeability and retention effect, liposome, paclitaxel, ovarian cancer
format	article
author	Shen YA Shyu IL Lu M He CL Hsu YM Liang HF Liu CP Liu RS Shen BJ Wei YH Chuang CM
author_facet	Shen YA Shyu IL Lu M He CL Hsu YM Liang HF Liu CP Liu RS Shen BJ Wei YH Chuang CM
author_sort	Shen YA
title	Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control
title_short	Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control
title_full	Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control
title_fullStr	Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control
title_full_unstemmed	Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control
title_sort	bypassing the epr effect with a nanomedicine harboring a sustained-release function allows better tumor control
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/8d0c59114b61491db7f9bfa91ecbee87
work_keys_str_mv	AT shenya bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT shyuil bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT lum bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT hecl bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT hsuym bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT lianghf bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT liucp bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT liurs bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT shenbj bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT weiyh bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol AT chuangcm bypassingtheepreffectwithananomedicineharboringasustainedreleasefunctionallowsbettertumorcontrol
_version_	1718401021228613632

Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control

Ejemplares similares