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Targeting Dysfunctional Vascular Endothelial Cells Using Immunoliposomes Under Flow Conditions.

Mahsa Kheradmandi1, Ian Ackers2,3, Monica M Burdick1,3

  • 1Department of Chemical and Biomolecular Engineering, Ohio University, 161 Stocker Center, Athens, OH 45701 USA.

Cellular and Molecular Bioengineering
|May 20, 2020
PubMed
Summary

Targeted drug delivery for atherosclerosis (ATH) is improved using VCAM1-functionalized liposomes. These liposomes effectively target endothelial cells in ATH lesions, offering potential for enhanced therapeutic outcomes in cardiovascular disease.

Keywords:
AtherosclerosisCell adhesion moleculesDrug deliveryEndotheliumNanomedicine

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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.