Injectable Senolytic Hydrogel Depot for the Clearance of Senescent Cells

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Small molecule drugs often have poor solubility, limiting their therapeutic use.
• Hydrophobic drugs like navitoclax face challenges due to poor solubility and toxic side effects.
• Senescent cells play complex roles, necessitating localized elimination strategies.

Purpose of the Study:

• To formulate hydrophobic navitoclax into nanoparticles for local senolytic therapy.
• To develop an injectable hydrogel system for controlled navitoclax delivery.
• To assess the efficacy of navitoclax-loaded hydrogels in clearing senescent cells.

Main Methods:

• Navitoclax nanoparticles were prepared using solvent-antisolvent nanoprecipitation.
• Injectable polymer-nanoparticle (PNP) hydrogels were formulated with navitoclax nanoparticles.
• In vitro studies were conducted using senescent endothelial monolayers.

Main Results:

• Navitoclax nanoparticles with an approximate diameter of 110 nm were successfully prepared.
• The developed PNP hydrogels effectively encapsulated navitoclax nanoparticles, forming a local depot.
• Navitoclax-loaded PNP hydrogels demonstrated selective clearance of senescent cells in vitro.

Conclusions:

• Formulating lipophilic small molecules like navitoclax is crucial for improving drug delivery.
• Localized drug delivery strategies hold significant potential for enhancing senolytic therapies.
• Injectable hydrogels loaded with drug nanoparticles offer a promising approach for targeted treatment.