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Treatment of Ischemic Stroke by Atorvastatin-Loaded PEGylated Liposome

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Abstract

There is insufficient evidence on the effect of nanoparticles, particularly liposomes loaded with a statin, on acute ischemic stroke. We investigated the impact of atorvastatin-loaded PEG (polyethylene glycol) conjugated liposomes (LipoStatin) on the outcomes in rats with cerebral ischemia–reperfusion. PEGylated liposome loaded with atorvastatin was developed as a nanoparticle to specifically accumulate in an ischemic region and release the drug to ameliorate the harmful effects of the stroke. LipoStatin was administered to rats with transient middle cerebral artery occlusion through the tail vein immediately after reperfusion (LipoStatin group). LipoStatin efficiently accumulated at the cerebral ischemic injury site of the rat. The LipoStatin group showed a significantly reduced infarct volume (p < 0.01) in brain micro-MR imaging and improved neurological function recovery compared to the control group (p < 0.05). In addition, markedly improved brain metabolism using fluorine-18 fluorodeoxyglucose micro-PET/CT imaging was demonstrated in the LipoStatin group compared with the control group (p < 0.01). Mechanistically, as a result of evaluation through IL-1 beta, TNF-alpha, ICAM-1, and Iba-1 mRNA expression levels at 5 days after cerebral ischemia, LipoStatin showed significant anti-inflammatory effects. Protein expression of occludin, JAM-A, Caveolin-1, and eNOS by western blot at 3 days and fluorescent images at 7 days showed considerable recovery of blood–brain barrier breakdown and endothelial dysfunction. PEGylated LipoStatin can be more effectively delivered to the ischemic brain and may have significant neuroprotective effects. Thus, PEGylated LipoStatin can be further developed as a promising targeted therapy for ischemic stroke and other major vascular diseases.

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All supporting data for the article are available upon reasonable request from a qualified investigator.

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Funding

This work was supported by the Technology Innovation Program (or Industrial Strategic Technology Development Program-Development of Core Industrial Technology) (20003822, Development of Navigation System Technologies of MicroNano Robots with Drug for Brain Disease Therapy) funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea). This work was supported by a National Research Foundation of Korea Grant funded by the Korean Government (NRF-2021M3C1B8036779).

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Author notes

  1. Reju George Thomas and Ja-hae Kim contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Radiology, Chonnam National University Medical School and Hwasun Hospital, 322 Seoyang-Ro, Hwasun-Eup, Hwasun-Gun, Jeollanam-Do, 58128, South Korea

    Reju George Thomas & Yong-Yeon Jeong

  2. Department of Nuclear Medicine, Chonnam National University Medical School and Hospital, Gwangju, South Korea

    Ja-hae Kim

  3. Department of Neurology, Chonnam National University Medical School and Hwasun Hospital, 322 Seoyang-Ro, Hwasun-Eup, Hwasun-Gun, Jeollanam-Do, 58128, South Korea

    Ji-hye Kim & Kang-Ho Choi

  4. School of Integrated Technology, Gwangju Institute of Science and Technology, Gwangju, South Korea

    Jungwon Yoon

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  1. Reju George Thomas
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Correspondence to Kang-Ho Choi or Yong-Yeon Jeong.

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Thomas, R.G., Kim, Jh., Kim, Jh. et al. Treatment of Ischemic Stroke by Atorvastatin-Loaded PEGylated Liposome. Transl. Stroke Res. 15, 388–398 (2024). https://doi.org/10.1007/s12975-023-01125-9

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