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Thoracic interstitial injection of drug-liposomes in mice for treating atherosclerosis

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Abstract

Intervaginal space injection (ISI) is a novel mode of administration investigated over the last decade. After injecting nanoparticles into the intervaginal space, they can be transported along low flow resistance channels into the interstitial space. This transport has a certain delivery direction, and site-specific injection can work on specific organs or tissues. In this study, the thorax, a new ISI site in the interstitial surrounding the internal thoracic artery named the thoracic interstitial injection (tISI) was investigated. To prove the targeting ability of the tISI, two sizes of gold nanoparticles (AuNPs) (47 and 87 nm) were administered to mice. After 1 h, the biodistribution of AuNPs in the tissues was measured via single particle inductively coupled plasma mass spectrometry (spICP-MS). The results showed that the concentration of AuNPs in the aorta after tISI injection was significantly higher than that after intravenous injection. Moreover, fewer nanoparticles with larger particle sizes were observed to have entered the blood and were better targeted to the aorta. Thereafter, tanshinone IIa sodium sulfonate liposomes were administered for the treatment of aortic atherosclerosis. The proportion of aortic plaques in atherosclerotic Apoe-/- mice administered via tISI was significantly lower than that in other model animals (P < 0.001). Furthermore, the proteoglycan content and CD68-positive cell count in the plaques were significantly reduced. The vascular elastic fibers at the plaque site were thickened, and fractures were reduced. tISI was, therefore, determined to be an effective strategy for the treatment of atherosclerotic aortic plaques.

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Acknowledgements

This work was supported by the Key Research Program of Frontier Science of CAS (No. ZDBS-LY-SLH036) and Key deployment projects of CAS (No. QYKJZD-SSW-SLH02).

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Authors and Affiliations

  1. College of Life Science, Beijing University of Chinese Medicine, Beijing, 100029, China

    Tun Yan, Huizhen Sun, Yahong Shi, Xi Lu, Kai Li, Tingting Li, Yuting Guo, Yinglu Ji & Dong Han

  2. CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China

    Tun Yan, Huizhen Sun, Yahong Shi, Ya Gao, Xi Lu, Kai Li, Yuting Zhu, Tingting Li, Zhongxian Li, Xiaohan Zhou, Xiaoli Shi & Dong Han

  3. College of Pharmacy, Baotou Medical College, Baotou, 10040, China

    Tun Yan

  4. Hebei Key Laboratory of Nanobiotechnology, Yanshan University, Qinhuangdao, 066004, China

    Qiang Zhang

  5. University of Chinese Academy of Sciences, Beijing, 100049, China

    Xiaoli Shi & Dong Han

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Yan, T., Sun, H., Shi, Y. et al. Thoracic interstitial injection of drug-liposomes in mice for treating atherosclerosis. Nano Res. 16, 5311–5321 (2023). https://doi.org/10.1007/s12274-022-5208-3

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