Anchoring β-CD on simvastatin-loaded rHDL for selective cholesterol crystals dissolution and enhanced anti-inflammatory effects in macrophage/foam cells.

Abstract

Macrophage/foam cells and cholesterol crystals (CCs) have been regarded as the central triggers of maladaptive inflammation in atherosclerotic plaque. Despite the tremendous progress of recombinant high-density lipoprotein (rHDL) serving for targeted drug delivery to alleviate inflammation in macrophage/foam cells, the active attempt to modulate/improve its CCs dissolution capacity remains poorly explored. The untreated CCs can seriously aggravate inflammation and threaten plaque stability. Based on the superb ability of β-cyclodextrin (β-CD) to bind CCs and promote cholesterol efflux, simvastatin-loaded discoidal-rHDL (ST-d-rHDL) anchored with β-CD (βCD-ST-d-rHDL) was constructed. We verified that βCD-ST-d-rHDL specifically bound and dissolved CCs extracellularly and intracellularly. Furthermore, anchoring β-CD onto the surface of ST-d-rHDL enhanced its cholesterol removal ability in RAW 264.7 cell-derived foam cells characterized by accelerated cholesterol efflux, reduced intracellular lipid deposition, and improved cell membrane fluidity/permeability. Finally, βCD-ST-d-rHDL exerted efficient drug delivery and effective anti-inflammatory effects in macrophage/foam cells. Collectively, anchoring β-CD onto the surface of ST-d-rHDL for selective CCs dissolution, accelerated cholesterol efflux, and improved drug delivery represents an effective strategy to enhance anti-inflammatory effects for the therapy of atherosclerosis.

• Authors: Jianhua He, Xiaoju Zhou, Fengfei Xu, Hongliang He, Shuangyan Ma, Xinyue Liu, Mengyuan Zhang, Wenli Zhang, Jianping Liu
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 174 Pg. 144-154 (May 2022) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 35447349 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Lipoproteins, HDL
• beta-Cyclodextrins
• Cholesterol
• Simvastatin

Topics

• Anti-Inflammatory Agents (metabolism, pharmacology)
• Atherosclerosis (drug therapy)
• Cholesterol (metabolism)
• Foam Cells (metabolism)
• Humans
• Inflammation (drug therapy, metabolism)
• Lipoproteins, HDL (chemistry)
• Macrophages
• Plaque, Atherosclerotic
• Simvastatin (pharmacology)
• Solubility
• beta-Cyclodextrins