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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Qiu X, Cao K, Lin T, Chen W, Yuan A, Wu J, Hu Y, Guo H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	bladder cancer intravesical instillation chemotherapy dendrimer PAMAM penetration acid microenvironment target-releasing Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fba4d90ef90a4ef2a3d5b2c20a6294db
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fba4d90ef90a4ef2a3d5b2c20a6294db
record_format	dspace
spelling	oai:doaj.org-article:fba4d90ef90a4ef2a3d5b2c20a6294db2021-12-02T08:07:46ZDrug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation1178-2013https://doaj.org/article/fba4d90ef90a4ef2a3d5b2c20a6294db2017-10-01T00:00:00Zhttps://www.dovepress.com/drug-delivery-system-based-on-dendritic-nanoparticles-for-enhancement--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xuefeng 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-releasingQiu XCao KLin TChen WYuan AWu JHu YGuo HDove Medical Pressarticlebladder cancerintravesical instillationchemotherapydendrimerPAMAMpenetrationacid microenvironmenttarget-releasingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7365-7374 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	bladder cancer intravesical instillation chemotherapy dendrimer PAMAM penetration acid microenvironment target-releasing Medicine (General) R5-920
spellingShingle	bladder cancer intravesical instillation chemotherapy dendrimer PAMAM penetration acid microenvironment target-releasing Medicine (General) R5-920 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
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
format	article
author	Qiu X Cao K Lin T Chen W Yuan A Wu J Hu Y Guo H
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
publishDate	2017
url	https://doaj.org/article/fba4d90ef90a4ef2a3d5b2c20a6294db
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_	1718398640513351680

Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation

Ejemplares similares