Targeting Dysfunctional Vascular Endothelial Cells Using Immunoliposomes Under Flow Conditions.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Atherosclerosis (ATH) is a leading cause of heart attack and stroke, driven by arterial plaque buildup.
• Current treatments suffer from drug instability and lack of target specificity.
• Targeted drug delivery to VCAM1-overexpressing endothelial cells in ATH lesions offers a promising therapeutic strategy.

Purpose of the Study:

• To develop and characterize VCAM1-functionalized liposomes for targeted delivery to atherosclerotic lesions.
• To evaluate the targeting efficiency of these liposomes under static and dynamic flow conditions.

Main Methods:

• Liposomes were synthesized with specific lipid compositions and functionalized with anti-VCAM1 antibodies.
• VCAM1 expression was induced in endothelial cells using lipopolysaccharide (LPS).
• Liposome targeting was assessed in vitro under static conditions and under flow mimicking physiological conditions, with and without erythrocytes.

Main Results:

• Synthesized liposomes were negatively charged with an average diameter of ~200 nm and exhibited no toxicity.
• Liposomes demonstrated effective targeting of endothelial cells, with higher efficiency under static vs. dynamic conditions.
• Targeting efficiency was reduced five-fold under flow conditions compared to static conditions, but remained effective in the presence or absence of erythrocytes.

Conclusions:

• VCAM1-functionalized liposomes show improved localization on dysfunctional endothelium.
• This liposomal delivery system holds potential for targeted delivery of therapeutics to atherosclerotic regions.
• Further development could enhance therapeutic efficacy for cardiovascular diseases.