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Cited by 62Nanoparticle-Based Drug DeliveryFlavonoids in Medical ResearchBarrier Structure and Function Studies

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Effect of Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody on regulating the levels of baicalin and amino acids during cerebral ischemia–reperfusion in rats

Liu, Zhidong, Zhang, Li, He, Qiansong, Liu, Xiaolei, Chukwunweike Ikechukwu, Okeke, Tong, Ling, Guo, Lili, Yang, Hongyun, Zhang, Qian, Zhao, Hainan, Gu, Xing·2015·International Journal of Pharmaceutics
DOI 10.1016/j.ijpharm.2015.04.049
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Abstract

Baicalin has many pharmacological activities, including neuroprotective function against ischemia and neurodegeneration. In our previous study, we found that Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody (OX26-PEG-CSLN) might be a promising carrier to deliver drugs across the blood-brain barrier for the treatment of brain diseases. So, the aim of this present study was to further elucidate the mechanisms of OX26-PEG-CSLN cerebral ischemia protection by monitoring the changes of extracellular amino acids. In addition, we investigated the effect of OX26-PEG-CSLN on the excitotoxic neuronal injury as well as the pharmacokinetic profiles of baicalin in cerebrospinal fluid during ischemia-reperfusion period. The cerebrospinal fluid was collected by a microdialysis technique and divided into two parts - one part for pharmacokinetic study of baicalin using LC-MS/MS method and the other for pharmacodynamic study which was done by pre- column derivatization of the amino acids and analysis using a high-performance liquid chromatography with fluorescence detector (HPLC-FLD). The pharmacokinetic study showed that the AUC value of OX26-PEG-CSLN was 5.69-fold higher than that of the baicalin solution (Sol) (P<0.05) and the Cmax value of OX26-PEG-CSLN was 6.84-fold higher than that of the Sol (P<0.05). Moreover, the extracellular levels of glutamate (Glu), aspartic acid (Asp), glycine (Gly), taurine (Tau) and γ-aminobutyric acid (GABA) were measured for monitoring the imbalance of amino acids caused by ischemia and reperfusion. The excitotoxic index (EI) was also calculated for evaluating the imbalance between excitatory amino acid and inhibitory amino acid. The pharmacodynamic study showed that OX26-PEG-CSLN had stronger effect than Sol in reducing the content of aspartic, glutamic acid and increasing the concentrations of glycine, taurine and γ-aminobutyric acid during ischemia-reperfusion period. In conclusion, OX26-PEG-CSLN improved uptake of baicalin across the BBB into the brain, and elevated bioavailability of baicalin in cerebral spinal fluid of rats under the cerebral ischemia-reperfusion injury. OX26-PEG-CSLN had much higher protection effect against cerebral ischemia injury than Sol by relieving the excitotoxic neuronal injury via regulating amino acid levels in cerebral spinal fluid.

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Metadata

Authors
Liu, Z., Zhang, L., He, Q., Liu, X., Chukwunweike Ikechukwu, O., Tong, L., Guo, L., Yang, H., Zhang, Q., Zhao, H., & Gu, X.
Affiliations
Tianjin University of Traditional Chinese Medicine (CN)
Corresponding author
Liu, Zhidong
ORCID
Venue
International Journal of Pharmaceutics
Publisher
Elsevier BV
Published
2015-07
Volume
489
Issue
1-2
Pages
131-138
ISSN
0378-5173 (ISSN-L)
DOI
10.1016/j.ijpharm.2015.04.049
OpenAlex
W2068312338
Cited by
62
References
0
Citations by year
2026: 2 · 2025: 5 · 2024: 12 · 2023: 5 · 2022: 10 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 1
FWCI
1.81
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • International Journal of Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81001645)
  • Program for New Century Excellent Talents in University (NCET-12-1068)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
baicalin, blood-brain barrier drug delivery, cerebral ischemia-reperfusion injury, neuroprotection, extracellular amino acids, excitotoxicity, cerebrospinal fluid pharmacokinetics, glutamate, glycine, GABA
MeSH terms
Amino Acids, Animals, Antibodies, Brain, Brain Ischemia, Flavonoids, Lipids, Male, Polyethylene Glycols, Reperfusion Injury, Rats, Sprague-Dawley, Nanoparticles

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