Back to Search
Start Over
Complement Receptor Targeted Liposomes Encapsulating the Liver X Receptor Agonist GW3965 Accumulate in and Stabilize Atherosclerotic Plaques
- Source :
- Advanced healthcare materials, 9(10). John Wiley and Sons Ltd, Advanced Healthcare Materials, 9(10), 2000043. WILEY, Advanced Healthcare Materials
- Publication Year :
- 2020
- Publisher :
- WILEY, 2020.
-
Abstract
- Atherosclerosis is characterized by the retention of lipids in foam cells in the arterial intima. The liver X receptor (LXR) agonist GW3965 is a promising therapeutic compound, since it induces reverse cholesterol transport in foam cells. However, hepatic LXR activation increases plasma and liver lipid levels, inhibiting its clinical development. Herein, a formulation that specifically enhances GW3965 deposition in the atherosclerotic lesion is aimed to be developed. GW3965 is encapsulated in liposomes functionalized with the cyclic peptide Lyp-1 (CGNKRTRGC), which binds the p32 receptor expressed on foam cells. These liposomes show preferential uptake by foam cells in vitro and higher accumulation in atherosclerotic plaques in mice compared to non-targeted liposomes as determined by in vivo imaging. Flow cytometry analysis of plaques reveals increased retention of Lyp-1 liposomes in atherosclerotic plaque macrophages compared to controls (p < 0.05). Long term treatment of established plaques in LDLR -/- mice with GW3965-containing Lyp-1 liposomes significantly reduces plaque macrophage content by 50% (p < 0.01). Importantly, GW3965-containing Lyp-1 liposomes do not increase plasma or hepatic lipid content. Thus, GW3965-containing Lyp-1 liposomes successfully target the atherosclerotic macrophages allowing plaque stabilization without commonly observed side effects of LXR agonists.
- Subjects :
- Agonist
liposomes
Benzylamines
medicine.drug_class
Biomedical Engineering
Pharmaceutical Science
02 engineering and technology
Complement receptor
Pharmacology
Lyp-1
010402 general chemistry
01 natural sciences
Benzoates
Biomaterials
Mice
medicine
Macrophage
Animals
Liver X receptor
Receptor
Foam cells
Liver X Receptors
Liposome
Chemistry
Reverse cholesterol transport
021001 nanoscience & nanotechnology
Atherosclerosis
Plaque, Atherosclerotic
foam cells
0104 chemical sciences
Receptors, Complement
LDL receptor
Liposomes
lipids (amino acids, peptides, and proteins)
atherosclerosis
0210 nano-technology
liver X receptor
Subjects
Details
- Language :
- English
- ISSN :
- 21922640
- Database :
- OpenAIRE
- Journal :
- Advanced healthcare materials, 9(10). John Wiley and Sons Ltd, Advanced Healthcare Materials, 9(10), 2000043. WILEY, Advanced Healthcare Materials
- Accession number :
- edsair.doi.dedup.....49a7965ad0727b86570d3f7128a99114