Rapamycin-Loaded Biomimetic Nanoparticles Reverse Vascular Inflammation.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Vascular inflammation drives atherosclerosis progression.
• Targeted drug delivery systems are needed to reduce systemic side effects.
• Rapamycin is an immunosuppressant with potential anti-inflammatory effects in vascular disease.

Purpose of the Study:

• To evaluate the efficacy of rapamycin-loaded biomimetic nanoparticles (leukosomes) for treating atherosclerosis.
• To assess the ability of leukosomes to reduce vascular inflammation and macrophage proliferation in vivo.
• To determine the safety and toxicity profile of this novel drug delivery system.

Main Methods:

• Biomimetic nanoparticles (leukosomes) were synthesized using macrophage membrane proteins.
• Rapamycin-loaded leukosomes were characterized for size, charge, and polydispersity.
• Atherosclerosis was induced in ApoE-/- mice fed a high-fat diet.
• Mice received daily injections of PBS, free rapamycin, or rapamycin-loaded leukosomes for 7 days.

Main Results:

• Leukosome treatment significantly reduced proliferating macrophages in the aorta compared to controls.
• Rapamycin-loaded leukosomes decreased levels of monocyte chemoattractant protein-1 and interleukin-1 beta.
• Aortic matrix metalloproteinase activity was significantly reduced in the leukosome-treated group.
• No significant adverse effects were observed in liver metabolic or inflammation assays.

Conclusions:

• Biomimetic nanoparticles effectively deliver rapamycin to suppress macrophage proliferation in atherosclerosis.
• The 7-day dosing schedule demonstrated a favorable toxicity profile.
• This platform offers a promising strategy for the acute stabilization of late-stage atherosclerotic plaques.