Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement

ChunYan Li,1 ZhiGang Huang,2 ZheShuo Liu,1 LiQian Ci,3 ZhePeng Liu,3 Yu Liu,2 XueYing Yan,1 WeiYue Lu2 1School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 2Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Edu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Li CY, Huang ZG, Liu ZS, Ci LQ, Liu ZP, Liu Y, Yan XY, Lu WY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Mucoadhesion phenylboronic acid stability controlled-release protein therapeutics nanoparticles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/146123e0df6545a59a78a646daf24f2f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:146123e0df6545a59a78a646daf24f2f
record_format	dspace
spelling	oai:doaj.org-article:146123e0df6545a59a78a646daf24f2f2021-12-02T02:38:20ZSulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement1178-2013https://doaj.org/article/146123e0df6545a59a78a646daf24f2f2016-11-01T00:00:00Zhttps://www.dovepress.com/sulfonate-modified-phenylboronic-acid-rich-nanoparticles-as-a-novel-mu-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013ChunYan Li,1 ZhiGang Huang,2 ZheShuo Liu,1 LiQian Ci,3 ZhePeng Liu,3 Yu Liu,2 XueYing Yan,1 WeiYue Lu2 1School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 2Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 3School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China Abstract: Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery system for vaginal administration of protein therapeutics. Keywords: mucoadhesion, phenylboronic acid, stability, controlled-release, protein therapeutics, nanoparticlesLi CYHuang ZGLiu ZSCi LQLiu ZPLiu YYan XYLu WYDove Medical PressarticleMucoadhesionphenylboronic acidstabilitycontrolled-releaseprotein therapeuticsnanoparticlesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 5917-5930 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mucoadhesion phenylboronic acid stability controlled-release protein therapeutics nanoparticles Medicine (General) R5-920
spellingShingle	Mucoadhesion phenylboronic acid stability controlled-release protein therapeutics nanoparticles Medicine (General) R5-920 Li CY Huang ZG Liu ZS Ci LQ Liu ZP Liu Y Yan XY Lu WY Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement
description	ChunYan Li,1 ZhiGang Huang,2 ZheShuo Liu,1 LiQian Ci,3 ZhePeng Liu,3 Yu Liu,2 XueYing Yan,1 WeiYue Lu2 1School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 2Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 3School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China Abstract: Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery system for vaginal administration of protein therapeutics. Keywords: mucoadhesion, phenylboronic acid, stability, controlled-release, protein therapeutics, nanoparticles
format	article
author	Li CY Huang ZG Liu ZS Ci LQ Liu ZP Liu Y Yan XY Lu WY
author_facet	Li CY Huang ZG Liu ZS Ci LQ Liu ZP Liu Y Yan XY Lu WY
author_sort	Li CY
title	Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement
title_short	Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement
title_full	Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement
title_fullStr	Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement
title_full_unstemmed	Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement
title_sort	sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/146123e0df6545a59a78a646daf24f2f
work_keys_str_mv	AT licy sulfonatemodifiedphenylboronicacidrichnanoparticlesasanovelmucoadhesivedrugdeliverysystemforvaginaladministrationofproteintherapeuticsimprovedstabilitymucindependentreleaseandeffectiveintravaginalplacement AT huangzg sulfonatemodifiedphenylboronicacidrichnanoparticlesasanovelmucoadhesivedrugdeliverysystemforvaginaladministrationofproteintherapeuticsimprovedstabilitymucindependentreleaseandeffectiveintravaginalplacement AT liuzs sulfonatemodifiedphenylboronicacidrichnanoparticlesasanovelmucoadhesivedrugdeliverysystemforvaginaladministrationofproteintherapeuticsimprovedstabilitymucindependentreleaseandeffectiveintravaginalplacement AT cilq sulfonatemodifiedphenylboronicacidrichnanoparticlesasanovelmucoadhesivedrugdeliverysystemforvaginaladministrationofproteintherapeuticsimprovedstabilitymucindependentreleaseandeffectiveintravaginalplacement AT liuzp sulfonatemodifiedphenylboronicacidrichnanoparticlesasanovelmucoadhesivedrugdeliverysystemforvaginaladministrationofproteintherapeuticsimprovedstabilitymucindependentreleaseandeffectiveintravaginalplacement AT liuy sulfonatemodifiedphenylboronicacidrichnanoparticlesasanovelmucoadhesivedrugdeliverysystemforvaginaladministrationofproteintherapeuticsimprovedstabilitymucindependentreleaseandeffectiveintravaginalplacement AT yanxy sulfonatemodifiedphenylboronicacidrichnanoparticlesasanovelmucoadhesivedrugdeliverysystemforvaginaladministrationofproteintherapeuticsimprovedstabilitymucindependentreleaseandeffectiveintravaginalplacement AT luwy sulfonatemodifiedphenylboronicacidrichnanoparticlesasanovelmucoadhesivedrugdeliverysystemforvaginaladministrationofproteintherapeuticsimprovedstabilitymucindependentreleaseandeffectiveintravaginalplacement
_version_	1718402271087165440

Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement

Ejemplares similares