Polyphenol-Functionalized Cubosomes as Thrombolytic Drug Carriers

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Thrombolytic agent administration for acute thrombosis poses safety challenges.
• Lipid-based nanoparticle drug delivery offers potential for improved thrombolytic therapy outcomes and safety.

Purpose of the Study:

• To investigate lipid cubosomes as nanocarriers for thrombolytic drugs.
• To evaluate the efficacy and safety of urokinase-type plasminogen activator (uPA)-loaded, peptide-coated cubosomes.

Main Methods:

• Lipid cubosomes were loaded with uPA and coated with a peptide-containing metal-phenolic network (pep-MPN).
• In vitro plasminogen activation and ex vivo whole blood clot degradation assays were performed.
• In vivo studies assessed cell association, circulation half-life, and splenic accumulation in mice.

Main Results:

• Pep-MPN-coated cubosomes demonstrated cell membrane-dependent thrombolytic activity due to fusogenic lipid behavior.
• Coated cubosomes showed significantly reduced nonspecific cell association (<10% of uncoated).
• Prolonged circulating half-life and reduced splenic uPA accumulation were observed in mice.

Conclusions:

• Pep-MPN-coated lipid cubosomes preserve uPA bioactivity and enable cell membrane-dependent release.
• These nanocarriers represent a promising delivery system for enhanced thrombolytic therapy with improved safety profiles.