A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery

Abstract

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.

Metadata

Item Type:	Article
Authors/Creators:	Zheng, B. Zhang, H. Wang, J. Qin, X. Xu, W. Wang, H. Liu, Z. Liu, Y. Mou, Y. Lai, W.-F. https://orcid.org/0000-0003-0585-6396 Shen, Y. Zhang, D. Zhang, P.
Copyright, Publisher and Additional Information:	© The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Keywords:	Mucoadhesive; Mucus-penetrating; Nanomotors; Intravesical therapy
Dates:	Published: 14 September 2024 Published (online): 14 September 2024 Accepted: 29 August 2024
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	19 Sep 2024 14:53
Last Modified:	19 Sep 2024 14:53
Status:	Published
Publisher:	Springer
Identification Number:	10.1186/s12951-024-02816-7
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:217356

Download

Published Version

Filename: s12951-024-02816-7.pdf

Licence: CC-BY-NC-ND 4.0

CLICK TO DOWNLOAD

CORE (COnnecting REpositories)

A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery

Abstract

Metadata

Download

Published Version

Export

Statistics