Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure

Na Wu,1,2,* Xinxin Zhang,2,* Feifei Li,2 Tao Zhang,2 Yong Gan,2 Juan Li1 1School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China *These au...

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Autores principales:	Wu N, Zhang XX, Li FF, Zhang T, Gan Y, Li J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3f5ec997ea8c4fc8b422fc217e9b070b
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spelling	oai:doaj.org-article:3f5ec997ea8c4fc8b422fc217e9b070b2021-12-02T00:10:22ZSpray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure1178-2013https://doaj.org/article/3f5ec997ea8c4fc8b422fc217e9b070b2015-08-01T00:00:00Zhttp://www.dovepress.com/spray-dried-powders-enhance-vaginal-sirna-delivery-by-potentially-modu-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Na Wu,1,2,* Xinxin Zhang,2,* Feifei Li,2 Tao Zhang,2 Yong Gan,2 Juan Li1 1School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5–15 µm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery. Keywords: siRNA delivery, vaginal administration, spray-dried powders, mucus penetration, molecular sieve effectWu NZhang XXLi FFZhang TGan YLi JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5383-5396 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wu N Zhang XX Li FF Zhang T Gan Y Li J Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure
description	Na Wu,1,2,* Xinxin Zhang,2,* Feifei Li,2 Tao Zhang,2 Yong Gan,2 Juan Li1 1School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5–15 µm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery. Keywords: siRNA delivery, vaginal administration, spray-dried powders, mucus penetration, molecular sieve effect
format	article
author	Wu N Zhang XX Li FF Zhang T Gan Y Li J
author_facet	Wu N Zhang XX Li FF Zhang T Gan Y Li J
author_sort	Wu N
title	Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure
title_short	Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure
title_full	Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure
title_fullStr	Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure
title_full_unstemmed	Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure
title_sort	spray-dried powders enhance vaginal sirna delivery by potentially modulating the mucus molecular sieve structure
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/3f5ec997ea8c4fc8b422fc217e9b070b
work_keys_str_mv	AT wun spraydriedpowdersenhancevaginalsirnadeliverybypotentiallymodulatingthemucusmolecularsievestructure AT zhangxx spraydriedpowdersenhancevaginalsirnadeliverybypotentiallymodulatingthemucusmolecularsievestructure AT liff spraydriedpowdersenhancevaginalsirnadeliverybypotentiallymodulatingthemucusmolecularsievestructure AT zhangt spraydriedpowdersenhancevaginalsirnadeliverybypotentiallymodulatingthemucusmolecularsievestructure AT gany spraydriedpowdersenhancevaginalsirnadeliverybypotentiallymodulatingthemucusmolecularsievestructure AT lij spraydriedpowdersenhancevaginalsirnadeliverybypotentiallymodulatingthemucusmolecularsievestructure
_version_	1718403858723504128

Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure

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