Nose-to-brain delivery of borneol modified tanshinone IIA nanoparticles in prevention of cerebral ischemia/reperfusion injury

Targeted treatment of cerebral ischemia/reperfusion injury (CIRI) remains a problem due to the difficulty in drug delivery across the blood-brain barrier (BBB). In this study, we developed Bo-TSA-NP, a novel tanshinone IIA (TSA) loaded nanoparticles modified by borneol, which has long been proved wi...

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Published inDrug delivery Vol. 28; no. 1; pp. 1363 - 1375
Main Authors Wang, Luting, Xu, Lin, Du, Junfeng, Zhao, Xiao, Liu, Mei, Feng, Jianfang, Hu, Kaili
Format Journal Article
LanguageEnglish
Published Philadelphia Taylor & Francis 01.01.2021
Taylor & Francis Ltd
Taylor & Francis Group
Subjects
Apoptosis
Biocompatibility
borneol
Brain diseases
Brain research
cerebral ischemia/reperfusion injury
Chinese medicine
Disease prevention
Drug delivery systems
Free radicals
Glycoproteins
Integrative medicine
Interdisciplinary aspects
intranasal delivery
Ischemia
Medical research
Nanoparticles
Particle size
PEG-PLGA nanoparticles
Stroke
tanshinone IIA
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Summary:Targeted treatment of cerebral ischemia/reperfusion injury (CIRI) remains a problem due to the difficulty in drug delivery across the blood-brain barrier (BBB). In this study, we developed Bo-TSA-NP, a novel tanshinone IIA (TSA) loaded nanoparticles modified by borneol, which has long been proved with the ability to enhance other drugs' transport across the BBB. The Bo-TSA-NP, with a particle size of about 160 nm, drug loading of 3.6%, showed sustained release and P-glycoprotein (P-gp) inhibition property. It demonstrated a significantly higher uptake by 16HBE cells in vitro through the clathrin/caveolae-mediated endocytosis and micropinocytosis. Following intranasal (IN) administration, Bo-TSA-NP significantly improved the preventive effect on a rat model of CIRI with improved neurological scores, decreased cerebral infarction areas and a reduced content of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) in rat brain. In conclusion, these results indicate that Bo-TSA-NP is a promising nose-to-brain delivery system that can enhance the prevention effect of TSA on CIRI.
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Jianfang Feng and Kaili Hu should be regarded as co-corresponding authors.
Both authors contributed equally to this work and should be regarded as co-first authors.
ISSN:1071-7544
1521-0464
DOI:10.1080/10717544.2021.1943058