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Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles

Li, G; He, S; Schätzlein, AG; Weiss, RM; Martin, DT; Uchegbu, IF; (2021) Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles. Journal of Controlled Release , 332 pp. 210-224. 10.1016/j.jconrel.2021.02.007. (In press).

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Uchegbu_Li et al. 2021.pdf - Accepted version
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Abstract

Short dwell-time and poor penetration of the bladder permeability barrier (BPB) are the main obstacles to intravesical treatments for bladder diseases, and is evidenced by the lack of such therapeutic options on the market. Herein, we demonstrate that by finely tuning the molecular weight of our cationic polymer mucoadhesive nanoparticles, we enhanced our gene transfer, leading to improved adherence and penetrance through the BPB in a safe and efficient manner. Specifically, increasing the polymer molecular weight from 45 kDa to 83 kDa enhanced luciferase plasmid transfer to the healthy murine bladder, leading to 1.35 ng/g luciferase protein expression in the urothelium and lamina propria regions. The relatively higher molecular weight polymer (83 kDa) did not induce morphologic changes or inflammatory responses in the bladder. This approach of altering polymer molecular weight for prolonging gene transfer residence time and deeper penetration through the BPB could be the basis for the design of future gene therapies for bladder diseases.

Type: Article
Title: Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles
Location: Netherlands
DOI: 10.1016/j.jconrel.2021.02.007
Publisher version: http://dx.doi.org/10.1016/j.jconrel.2021.02.007
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Bladder delivery, Chitosan derivatives, Gene therapy, Higher molecular weight, Nanoparticles, Non-viral vectors
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10123312
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