Citation: Xiaotong Li, Jiayi Gu, Qingqing Xiao, Ying Liu, Ping Zhou, Lifang Fan, Xiulian Zhang, Xiang Lu, Jun Wu, Zhengxia Liu, Wei He. Liposomal codelivery of inflammation inhibitor and collagen protector to the plaque for effective anti-atherosclerosis[J]. Chinese Chemical Letters, ;2023, 34(1): 107483. doi: 10.1016/j.cclet.2022.04.081 shu

Liposomal codelivery of inflammation inhibitor and collagen protector to the plaque for effective anti-atherosclerosis

Xiaotong Li ^{a, 1} ,
Jiayi Gu ^{b, c, 1} ,
Qingqing Xiao ^{a, 1} ,
Ying Liu ^{b, c, 1} ,
Ping Zhou ^{b, c} ,
Lifang Fan ^d ,
Xiulian Zhang ^e ,
Xiang Lu ^{b, c, g} ,
Jun Wu ^{f, *,} ,
Zhengxia Liu ^{b, c, **,} ,
Wei He ^{a, *,}

a.
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
b.
Department of Geriatrics, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 210011, China
c.
Key Laboratory for Aging & Disease, Nanjing Medical University, Nanjing 210011, China
d.
Jiangsu Aosaikang Pharmaceutical Co., Ltd., Nanjing 211112, China
e.
Department of Respiratory Disease, Baoshan Branch, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
f.
Department of Geriatric Cardiology, Jiangsu Provincial Key Laboratory of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
g.
Department of Geriatrics, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing 211166, China

^**

wujun9989@njmu.edu.cn

zhengxl1@njmu.edu.cn

weihe@cpu.edu.cn

Received Date: 27 December 2021
Revised Date: 27 April 2022
Accepted Date: 28 April 2022
Available Online: 2 May 2022

Figures(3)

Plaque plays a central role in atherosclerosis (AS) progression, whereas inflammation and destruction of the plaque microenvironment contribute to plaque advancement. As a result, a therapy regime, which combines anti-inflammation and inhibition-degradation of plaque matrix, appears to be a promising strategy to combat AS. Herein, we report a pH-sensitive liposome co-loading with the anti-inflammatory agent (oridonin, ORD) and plaque-collagen protector (marimastat) for anti-AS therapy. ORD was first conjugated with hyaluronic acid (HA) to target the inflammation contributor, pro-inflammatory macrophages. Then, the conjugate assembled onto the MATT-loaded liposomes. The co-loaded system (~150 nm) significantly improved pharmacokinetics over the liposomes without anchoring the conjugate and accumulated effectively in the plaque. The preparation administration allowed efficient anti-AS activities in high-fat diet (HFD)-Apoe^-/- mice by decreasing the pro-inflammatory cytokine expression in the serum, lessening the lesion area, alleviating the plaque collagen degradation, promoting macrophage polarization from phenotypic M1 to M2, reducing T helper (Th) 17 cells (Th17)/T regulatory cells (Tregs) and Th1/Th2 ratio, etc. Furthermore, the serum determination in AS patients demonstrated high expression of the inflammatory cytokines, indicating our finding may offer a potential guideline for clinical practice.
- Atherosclerosis,
- Plaque,
- Inflammation,
- Collagen,
- Macrophages,
- Co-delivery,
- Liposomes
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