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Geniposide-Loaded Liposomes for Brain Targeting: Development, Evaluation, and In Vivo Studies

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Abstract

Geniposide (GE) possesses excellent neuroprotective effects but with poor brain targeting and short half-life. Liposome was considered to have great potential for brain diseases. Therefore, this research aimed to develop a geniposide liposome (GE-LP) as a brain delivery system for cerebral ischemia reperfusion injury (CIRI) therapy and evaluate its characterization, pharmacokinetics, brain targeting, and neuroprotective effects in vivo. Then, a reverse-phase evaporation method was applied to develop the GE-LP and optimize the formulation. Notably, the GE-LP had suitable size, which was 223.8 nm. Subsequently, the pharmacokinetic behavior of GE solution and GE-LP in mice plasma was investigated, and the brain targeting was also researched. The results showed that GE in plasma of GE-LP displayed three folds longer distribution half-life and a higher bioavailability and brain targeting compared to GE solution. In vivo neuroprotective effects was evaluated through the middle cerebral artery occlusion (MCAO) rat model, and GE-LP exhibited a stronger tendency in preventing the injury of CIRI, which can significantly improve neurological deficits. Overall, this study demonstrates GE-LP as a new formulation with ease of preparation, sustained release, and high brain targeting, which has significant development prospects on CIRI; this is expected to improve the efficacy of GE and reduce the frequency of administration.

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Abbreviations

GE:

geniposide

GE-LP:

geniposide liposome

PA:

paeoniflorin

MCAO:

middle cerebral artery occlusion

CIRI:

cerebral ischemia reperfusion injury

NCS:

nerve center system

TCM:

traditional Chinese medicine

BBB:

blood-brain barrier

BBD:

Response Surface Box-Behnken design

TEM:

transmission electron microscopy

PDI:

polydispersity Index

EE:

entrapment efficiency

DL:

drug loading

DAD:

diode array detector

CCA:

common carotid artery

ICA:

internal carotid artery

ECA:

external carotid artery

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Funding

This research was funded by the National Natural Science Foundation of China, No: 81673615; the Sichuan Human Resources and Social Security Bureau, No: 00809503; the Xinglin Scholar Discipline Promotion Talent Program of Chengdu University of Traditional Chinese Medicine, No: XGZX2010; the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine, No: TCM-201908, and the National College Student Innovation and Entrepreneurship Training Program, No: S202010633055.

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Authors and Affiliations

  1. State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu, Sichuan, People’s Republic of China

    Jinyan Wan, Yu Long, Songyu Liu, Yulu Zhang, Yan Xiang, Dan Li, Ai Shi, Yu Shuang, Ying Li, Yanan He & Nan Li

  2. Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, No.1688, Meiling Road, Wanli District, Nanchang, Jiangxi, ,330004, People’s Republic of China

    Yongmei Guan

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  1. Jinyan Wan
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  2. Yu Long
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  3. Songyu Liu
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  10. Yanan He
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  11. Nan Li
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Contributions

Jinyan Wan, Nan Li, and Songyu Liu have substantial contributions to the conception or design of the work and the acquisition, analysis, or interpretation of data for the work; Jinyan Wan, Yu Long, and Yulu Zhang drafted the work and revised it critically for important intellectual content; Yan Xiang, Dan Li, Ai Shi, Yu Shuang, Yanan He, and Ying Li also revised it and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; Jinyan Wan, Nan Li, and Yongmei Guan finally approved the version to be published.

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Correspondence to Nan Li or Yongmei Guan.

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Wan, J., Long, Y., Liu, S. et al. Geniposide-Loaded Liposomes for Brain Targeting: Development, Evaluation, and In Vivo Studies. AAPS PharmSciTech 22, 222 (2021). https://doi.org/10.1208/s12249-021-02093-9

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