Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation
Xuefeng Qiu,1,2,* Kai Cao,1,2,* Tingsheng Lin,1,2 Wei Chen,1 Ahu Yuan,2 Jinhui Wu,2 Yiqiao Hu,2 Hongqian Guo1 1Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, China; 2State Key Laboratory of Pharmaceutical Biotechn...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2017-10-01
|
Series: | International Journal of Nanomedicine |
Subjects: | |
Online Access: | https://www.dovepress.com/drug-delivery-system-based-on-dendritic-nanoparticles-for-enhancement--peer-reviewed-article-IJN |
id |
doaj-fba4d90ef90a4ef2a3d5b2c20a6294db |
---|---|
record_format |
Article |
spelling |
doaj-fba4d90ef90a4ef2a3d5b2c20a6294db2020-11-24T21:35:51ZengDove Medical PressInternational Journal of Nanomedicine1178-20132017-10-01Volume 127365737435118Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillationQiu XCao KLin TChen WYuan AWu JHu YGuo HXuefeng Qiu,1,2,* Kai Cao,1,2,* Tingsheng Lin,1,2 Wei Chen,1 Ahu Yuan,2 Jinhui Wu,2 Yiqiao Hu,2 Hongqian Guo1 1Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, China; 2State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China *These authors contributed equally to this work Abstract: Intravesical instillation of antitumor agents following transurethral resection of bladder tumors is the standard strategy for the treatment of superficial bladder cancers. However, the efficacy of current intravesical instillation is limited partly due to the poor permeability of the urothelium. We therefore aimed to develop a high-penetrating, target-releasing drug delivery system to improve the efficacy of intravesical instillation. PAMAM, a dendrimer, were conjugated with polyethylene glycol (PEG) to form PEG-PAMAM complex as a nanocarrier. Doxorubicin (DOX) was then encapsulated into PEG-PAMAM to generate DOX-loaded PEG-PAMAM nanoparticles (PEG-PAMAM-DOX). Our results indicated that the PEG-PAMAM was a stable nanocarrier with small size and great biosafety. The release of DOX from PEG-PAMAM-DOX was sluggish but could be effectively triggered in an acid microenvironment (pH =5.0). As a drug carrier, PEG-PAMAM could penetrate mice bladder urothelium effectively and increase the amount of DOX within the bladder wall after intravesical instillation. The antitumor effect of PEG-PAMAM-DOX was evaluated using an orthotopic bladder cancer model in mice. Compared to free DOX, PEG-PAMAM-DOX showed significantly improved efficacy of DOX for intravesical instillation with limited side effects. In conclusion, we successfully developed a PEG-PAMAM-based drug delivery system to enhance the antitumor effect of intravesical instillation. Keywords: bladder cancer, intravesical instillation, chemotherapy, dendrimer, PAMAM, penetration, acid microenvironment, target-releasinghttps://www.dovepress.com/drug-delivery-system-based-on-dendritic-nanoparticles-for-enhancement--peer-reviewed-article-IJNbladder cancerintravesical instillationchemotherapydendrimerPAMAMpenetrationacid microenvironmenttarget-releasing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qiu X Cao K Lin T Chen W Yuan A Wu J Hu Y Guo H |
spellingShingle |
Qiu X Cao K Lin T Chen W Yuan A Wu J Hu Y Guo H Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation International Journal of Nanomedicine bladder cancer intravesical instillation chemotherapy dendrimer PAMAM penetration acid microenvironment target-releasing |
author_facet |
Qiu X Cao K Lin T Chen W Yuan A Wu J Hu Y Guo H |
author_sort |
Qiu X |
title |
Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation |
title_short |
Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation |
title_full |
Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation |
title_fullStr |
Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation |
title_full_unstemmed |
Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation |
title_sort |
drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation |
publisher |
Dove Medical Press |
series |
International Journal of Nanomedicine |
issn |
1178-2013 |
publishDate |
2017-10-01 |
description |
Xuefeng Qiu,1,2,* Kai Cao,1,2,* Tingsheng Lin,1,2 Wei Chen,1 Ahu Yuan,2 Jinhui Wu,2 Yiqiao Hu,2 Hongqian Guo1 1Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, China; 2State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China *These authors contributed equally to this work Abstract: Intravesical instillation of antitumor agents following transurethral resection of bladder tumors is the standard strategy for the treatment of superficial bladder cancers. However, the efficacy of current intravesical instillation is limited partly due to the poor permeability of the urothelium. We therefore aimed to develop a high-penetrating, target-releasing drug delivery system to improve the efficacy of intravesical instillation. PAMAM, a dendrimer, were conjugated with polyethylene glycol (PEG) to form PEG-PAMAM complex as a nanocarrier. Doxorubicin (DOX) was then encapsulated into PEG-PAMAM to generate DOX-loaded PEG-PAMAM nanoparticles (PEG-PAMAM-DOX). Our results indicated that the PEG-PAMAM was a stable nanocarrier with small size and great biosafety. The release of DOX from PEG-PAMAM-DOX was sluggish but could be effectively triggered in an acid microenvironment (pH =5.0). As a drug carrier, PEG-PAMAM could penetrate mice bladder urothelium effectively and increase the amount of DOX within the bladder wall after intravesical instillation. The antitumor effect of PEG-PAMAM-DOX was evaluated using an orthotopic bladder cancer model in mice. Compared to free DOX, PEG-PAMAM-DOX showed significantly improved efficacy of DOX for intravesical instillation with limited side effects. In conclusion, we successfully developed a PEG-PAMAM-based drug delivery system to enhance the antitumor effect of intravesical instillation. Keywords: bladder cancer, intravesical instillation, chemotherapy, dendrimer, PAMAM, penetration, acid microenvironment, target-releasing |
topic |
bladder cancer intravesical instillation chemotherapy dendrimer PAMAM penetration acid microenvironment target-releasing |
url |
https://www.dovepress.com/drug-delivery-system-based-on-dendritic-nanoparticles-for-enhancement--peer-reviewed-article-IJN |
work_keys_str_mv |
AT qiux drugdeliverysystembasedondendriticnanoparticlesforenhancementofintravesicalinstillation AT caok drugdeliverysystembasedondendriticnanoparticlesforenhancementofintravesicalinstillation AT lint drugdeliverysystembasedondendriticnanoparticlesforenhancementofintravesicalinstillation AT chenw drugdeliverysystembasedondendriticnanoparticlesforenhancementofintravesicalinstillation AT yuana drugdeliverysystembasedondendriticnanoparticlesforenhancementofintravesicalinstillation AT wuj drugdeliverysystembasedondendriticnanoparticlesforenhancementofintravesicalinstillation AT huy drugdeliverysystembasedondendriticnanoparticlesforenhancementofintravesicalinstillation AT guoh drugdeliverysystembasedondendriticnanoparticlesforenhancementofintravesicalinstillation |
_version_ |
1716692271031648256 |