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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Regulating the Size of Simvastatin-loaded Discoidal Reconstituted Highdensity Lipoprotein: Preparation, Characterization, and Investigation of Cellular Cholesterol Efflux

Author(s): Xinya Huang, Hai Gao, Wenli Zhang*, Jianping Liu* and Qiqi Zhang

Volume 20, Issue 5, 2023

Published on: 25 August, 2022

Page: [629 - 641] Pages: 13

DOI: 10.2174/1567201819666220414120901

Price: $65

Abstract

Background: Reverse cholesterol transportation is essential for high-density lipoprotein (HDL) particles to reduce the cholesterol burden of peripheral cells. Studies have shown that particle size plays a crucial role in the cholesterol efflux capacity of HDLs, and the reconstituted HDLs (rHDLs) possess a similar function to natural ones.

Objective: The study aimed to investigate the effect of particle size on the cholesterol efflux capacity of discoidal rHDLs and whether drug loadings may have an influence on this effect.

Methods: Different-sized simvastatin-loaded discoidal rHDLs (ST-d-rHDLs) resembling nascent HDL were prepared by optimizing key factors related to the sodium cholate of film dispersion-sodium cholate dialysis method with a single controlling factor. Their physicochemical properties, such as particle size, zeta potential, and morphology in vitro, were characterized, and their capacity of cellular cholesterol efflux in foam cells was evaluated.

Results: We successfully constructed discoidal ST-d-rHDLs with different sizes (13.4 ± 1.4 nm, 36.6 ± 2.6 nm, and 68.6 ± 3.8 nm) with over 80% of encapsulation efficiency and sustained drug release. Among them, the small-sized ST-d-rHDL showed the strongest cholesterol efflux capacity and inhibitory effect on intracellular lipid deposition in foam cells. In addition, the results showed that the loaded drug did not compromise the cellular cholesterol efflux capacity of different-sized ST-d-rHDL.

Conclusion: Compared to the larger-sized ST-d-rHDLs, the small-sized ST-d-rHDL possessed enhanced cellular cholesterol efflux capacity similar to drug-free one, and the effect of particle size on cholesterol efflux was not influenced by the drug loading.

Keywords: Particle size, discoidal reconstituted high-density lipoprotein, sodium cholate, cholesterol efflux, foam cells, apo AI.

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