Effect of cholesterol on distribution, cell uptake, and protein corona of lipid microspheres at sites of cardiovascular inflammatory injury

Lingyan Li; Xingjie Wu; Qianqian Guo; Yu'e Wang; Zhiyong He; Guangqiong Zhang; Shaobo Liu; Liping Shu; Babu Gajendran; Ying Chen; Xiangchun Shen; Ling Tao

doi:10.1016/j.jpha.2024.101182

Volume 15 Issue 7

Jul. 2025

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Article Navigation > Journal of Pharmaceutical Analysis > 2025 > 15(7): 101182

Lingyan Li, Xingjie Wu, Qianqian Guo, Yu'e Wang, Zhiyong He, Guangqiong Zhang, Shaobo Liu, Liping Shu, Babu Gajendran, Ying Chen, Xiangchun Shen, Ling Tao. Effect of cholesterol on distribution, cell uptake, and protein corona of lipid microspheres at sites of cardiovascular inflammatory injury[J]. Journal of Pharmaceutical Analysis, 2025, 15(7): 101182. doi: 10.1016/j.jpha.2024.101182

Citation:

Lingyan Li, Xingjie Wu, Qianqian Guo, Yu'e Wang, Zhiyong He, Guangqiong Zhang, Shaobo Liu, Liping Shu, Babu Gajendran, Ying Chen, Xiangchun Shen, Ling Tao. Effect of cholesterol on distribution, cell uptake, and protein corona of lipid microspheres at sites of cardiovascular inflammatory injury[J]. Journal of Pharmaceutical Analysis, 2025, 15(7): 101182. doi: 10.1016/j.jpha.2024.101182

Citation:

Lingyan Li, Xingjie Wu, Qianqian Guo, Yu'e Wang, Zhiyong He, Guangqiong Zhang, Shaobo Liu, Liping Shu, Babu Gajendran, Ying Chen, Xiangchun Shen, Ling Tao. Effect of cholesterol on distribution, cell uptake, and protein corona of lipid microspheres at sites of cardiovascular inflammatory injury[J]. Journal of Pharmaceutical Analysis, 2025, 15(7): 101182. doi: 10.1016/j.jpha.2024.101182

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Effect of cholesterol on distribution, cell uptake, and protein corona of lipid microspheres at sites of cardiovascular inflammatory injury

doi: 10.1016/j.jpha.2024.101182

Lingyan Li^a,b,c,
Xingjie Wu^a,b,c,
Qianqian Guo^a,b,c,
Yu'e Wang^a,b,c,
Zhiyong He^a,b,c,
Guangqiong Zhang^a,b,c,
Shaobo Liu^a,b,c,
Liping Shu^d,
Babu Gajendran^a,b,
Ying Chen^{a,b,c
,
,},
Xiangchun Shen^{a,b,c
,
,},
Ling Tao^{a,b,c
,
,}

a. State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 561113, China;
b. The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 561113, China;
c. Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City-Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 561113, China;
d. School of Basic Medicine, Guizhou Medical University, Guiyang, 561113, China

Funds:

This study was supported by the National Natural Science Foundation of China (Grant Nos.: 82260827 and U1812403-4-4), the Guizhou Provincial Science and Technology Projects, China (Grant Nos.: [2020]1Z069, ZK [2022]380, and ZK [2023]303), the Cultivation Project of National Natural Science Foundation of Guizhou Medical University, China (Grant No.: 20NSP050), the Guizhou Provincial Scientific and Technologic Innovation Base, China (Grant No.: [2023]003), the High-level Innovation Talents of Guizhou Province, China (Grant No.: GCC[2023]048), and the Startup Fund for High-Level Talent Research at Guizhou Medical University, China (Grant No.: 26242020107). We thank the National Joint Local Engineering Laboratory of Guizhou Medical University for cell engineering and biomedicine techniques as well as Guizhou Province Key Laboratory of Regenerative Medicine of Guizhou Medical University and Key Laboratory of Adult Stem Cell Translational Research of Chinese Academy of Medical Sciences for providing the support of the zebrafish experiment platform. Fig. 1 and Graphical abstract were drawn by using Figdraw (https://www.figdraw.com).

Received Date: Jul. 14, 2024
Accepted Date: Dec. 29, 2024
Rev Recd Date: Dec. 03, 2024
Publish Date: Jan. 03, 2025

Abstract

Abstract

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.
- Biological effects,
- Cellular kinetics,
- Cholesterol,
- Inflammation,
- Network pharmacology,
- Proteomics

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References(47)

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