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.