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Authors Yuan X, Fei F, Sun H, Xiao C, Zhao X, Zhang YJ, Zheng X
Received 13 December 2017
Accepted for publication 23 February 2018
Published 12 April 2018 Volume 2018:13 Pages 2265—2274
DOI https://doi.org/10.2147/IJN.S159789
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Govarthanan Muthusamy
Peer reviewer comments 2
Editor who approved publication: Dr Linlin Sun
Background: Tanshinol borneol ester (DBZ) is a hybrid of danshensu (DSS) and
borneol and has anti-ischemic activity in animals. However, its low water
solubility and short half-life limit its clinical application.
Methods: We prepared polyethylene glycol (PEG)-modified and DBZ-loaded
nanostructured lipid carriers (DBZ-PEG-NLC) and DBZ-NLC, and examined their
physical characteristics, such as particle size, zeta potential, entrapment
efficiency and drug loading. The in vitro stability and pharmacokinetics in
rats as well as antioxidant activity of DBZ-PEG-NLC and DBZ-NLC in a C57BL/6
mouse model of ischemia/reperfusion-related brain injury were investigated. The
levels of DBZ and its hydrolyzed DSS in rat plasma and brain microdialysates
were determined by liquid chromatography–mass spectroscopy/mass spectroscopy
analysis.
Results: We found that the mean particle size and entrapment efficacy of
DBZ-PEG-NLC were similar to that of DBZ-NLC. The DBZ-PEG-NLC, like DBZ-NLC,
released DBZ in a biphasic manner with initially burst release and then
prolonged slow release in vitro. Intravenous injection of DBZ-PEG-NLC resulted
in significantly higher levels and longer retention periods of DBZ and DSS in
plasma and the brains than DBZ-NLC and DBZ in rats. Finally, treatment with
DBZ-PEG-NLC achieved a better antioxidant activity than DBZ or DBZ-NLC in mouse
model of ischemia/reperfusion by reducing the levels of brain malondialdehyde,
but increasing the levels of brain superoxide dismutase and glutathione.
Conclusion: DBZ-PEG-NLC is a preferable option to deliver DBZ for sustainable
release of DSS and borneol in vivo, and may serve as a promising drug for
effective therapy of ischemic cardiovascular and cerebrovascular diseases.
Keywords: nanovesicles, pharmacokinetics, brain microdialysis, ischemic
cerebrovascular diseases, polyethylene glycol, danshensu