Effect of Lipid Composition on the Atheroprotective Properties of HDL-Mimicking Micelles
Atherosclerosis progression is driven by an imbalance of cholesterol and unresolved local inflammation in the arteries. The administration of recombinant apolipoprotein A-I (ApoA-I)-based high-density lipoprotein (HDL) nanoparticles has been used to reduce the size of atheroma and rescue inflammator...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/8/1570 |
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| author | Kristen Hong Minzhi Yu Julia Crowther Ling Mei Karl Olsen Yonghong Luo Yuqing Eugene Chen Yanhong Guo Anna Schwendeman |
| author_facet | Kristen Hong Minzhi Yu Julia Crowther Ling Mei Karl Olsen Yonghong Luo Yuqing Eugene Chen Yanhong Guo Anna Schwendeman |
| author_sort | Kristen Hong |
| collection | DOAJ |
| description | Atherosclerosis progression is driven by an imbalance of cholesterol and unresolved local inflammation in the arteries. The administration of recombinant apolipoprotein A-I (ApoA-I)-based high-density lipoprotein (HDL) nanoparticles has been used to reduce the size of atheroma and rescue inflammatory response in clinical studies. Because of the difficulty in producing large quantities of recombinant ApoA-I, here, we describe the preparation of phospholipid-based, ApoA-I-free micelles that structurally and functionally resemble HDL nanoparticles. Micelles were prepared using various phosphatidylcholine (PC) lipids combined with 1,2-distearoyl-<i>sn</i>-glycero-3-phosphoethanolamine-N-[azido(polyethylene glycol)-2000] (DSPE-PEG2k) to form nanoparticles of 15–30 nm in diameter. The impacts of PC composition and PEGylation on the anti-inflammatory activity, cholesterol efflux capacity, and cholesterol crystal dissolution potential of micelles were investigated in vitro. The effects of micelle composition on pharmacokinetics and cholesterol mobilization ability were evaluated in vivo in Sprague Dawley rats. The study shows that the composition of HDL-mimicking micelles impacts their overall atheroprotective properties and supports further investigation of micelles as a therapeutic for the treatment of atherosclerosis. |
| first_indexed | 2024-03-09T09:50:49Z |
| format | Article |
| id | doaj.art-49128b1a32864982a3d3eb88e56dab0b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T09:50:49Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-49128b1a32864982a3d3eb88e56dab0b2023-12-02T00:09:28ZengMDPI AGPharmaceutics1999-49232022-07-01148157010.3390/pharmaceutics14081570Effect of Lipid Composition on the Atheroprotective Properties of HDL-Mimicking MicellesKristen Hong0Minzhi Yu1Julia Crowther2Ling Mei3Karl Olsen4Yonghong Luo5Yuqing Eugene Chen6Yanhong Guo7Anna Schwendeman8Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USADepartment of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USADepartment of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USADepartment of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USADepartment of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USADepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI 48109, USADepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI 48109, USADepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI 48109, USADepartment of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USAAtherosclerosis progression is driven by an imbalance of cholesterol and unresolved local inflammation in the arteries. The administration of recombinant apolipoprotein A-I (ApoA-I)-based high-density lipoprotein (HDL) nanoparticles has been used to reduce the size of atheroma and rescue inflammatory response in clinical studies. Because of the difficulty in producing large quantities of recombinant ApoA-I, here, we describe the preparation of phospholipid-based, ApoA-I-free micelles that structurally and functionally resemble HDL nanoparticles. Micelles were prepared using various phosphatidylcholine (PC) lipids combined with 1,2-distearoyl-<i>sn</i>-glycero-3-phosphoethanolamine-N-[azido(polyethylene glycol)-2000] (DSPE-PEG2k) to form nanoparticles of 15–30 nm in diameter. The impacts of PC composition and PEGylation on the anti-inflammatory activity, cholesterol efflux capacity, and cholesterol crystal dissolution potential of micelles were investigated in vitro. The effects of micelle composition on pharmacokinetics and cholesterol mobilization ability were evaluated in vivo in Sprague Dawley rats. The study shows that the composition of HDL-mimicking micelles impacts their overall atheroprotective properties and supports further investigation of micelles as a therapeutic for the treatment of atherosclerosis.https://www.mdpi.com/1999-4923/14/8/1570micelleatherosclerosishigh-density lipoproteinsnanoparticlelipid composition |
| spellingShingle | Kristen Hong Minzhi Yu Julia Crowther Ling Mei Karl Olsen Yonghong Luo Yuqing Eugene Chen Yanhong Guo Anna Schwendeman Effect of Lipid Composition on the Atheroprotective Properties of HDL-Mimicking Micelles Pharmaceutics micelle atherosclerosis high-density lipoproteins nanoparticle lipid composition |
| title | Effect of Lipid Composition on the Atheroprotective Properties of HDL-Mimicking Micelles |
| title_full | Effect of Lipid Composition on the Atheroprotective Properties of HDL-Mimicking Micelles |
| title_fullStr | Effect of Lipid Composition on the Atheroprotective Properties of HDL-Mimicking Micelles |
| title_full_unstemmed | Effect of Lipid Composition on the Atheroprotective Properties of HDL-Mimicking Micelles |
| title_short | Effect of Lipid Composition on the Atheroprotective Properties of HDL-Mimicking Micelles |
| title_sort | effect of lipid composition on the atheroprotective properties of hdl mimicking micelles |
| topic | micelle atherosclerosis high-density lipoproteins nanoparticle lipid composition |
| url | https://www.mdpi.com/1999-4923/14/8/1570 |
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