Injectable Senolytic Hydrogel Depot for the Clearance of Senescent Cells
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Date
2025-02-10
Publication Type
Journal Article
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yes
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Abstract
Small molecules are frontline therapeutics for many diseases; however, they are often limited by their poor solubility. Therefore, hydrophobic small molecules are often encapsulated or prepared as pure drug nanoparticles. Navitoclax, used to eliminate senescent cells, is one such small molecule that faces challenges in translation due to its hydrophobicity and toxic side effects. Further, as senescent cells exhibit context-dependent pathologic or beneficial properties, it is preferable to eliminate senescent cells locally. To formulate navitoclax and enable local treatment, we designed an injectable hydrogel loaded with navitoclax nanoparticles as a senolytic delivery vehicle. Navitoclax nanoparticles (& Oslash; similar to 110 nm) were prepared via solvent-antisolvent nanoprecipitation and formulated in an injectable polymer-nanoparticle (PNP) hydrogel to create a local senolytic depot. Navitoclax-loaded PNP hydrogels selectively cleared senescent cells in vitro in senescent endothelial monolayers. This work demonstrates the value of formulating lipophilic small molecules and the potential of localized drug delivery strategies to improve senolytic therapies.
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published
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Book title
Journal / series
Volume
26 (2)
Pages / Article No.
814 - 824
Publisher
American Chemical Society
Event
Edition / version
Methods
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Date collected
Date created
Subject
Organisational unit
09472 - Tibbitt, Mark / Tibbitt, Mark
03605 - Mazza, Edoardo / Mazza, Edoardo
Notes
Funding
184697 - Next-generation moldable gels via combined polymer-colloid self-assembly and supramolecular chemistry (SNF)
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