| With the aging of the population and the improvement of living standards, the incidence of cardiovascular and cerebrovascular diseases has become the first killer of human health. Tanshinol borneol ester (DBZ) shows good curative effect in treating cardiovascular and cerebrovascular diseases. However, because of the short half-life in the body, the brain transmission of DBZ is low efficiency. In this study, we prepared a long circulating nanostructured lipid carriers of DBZ (PEG-DBZ-NLC) and investigated the pharmacokinetics and brain targeting properties of DBZ in rat. The main processes and results of this paper are as follows:1. DBZ-NLC and PEG-DBZ-NLC were prepared by organic solvent diffusion and high shear method. The formulation and processing paramaters of the nanoparticles were optimized by single factor investigation and orthogonal optimization method. The results showed that the average particle sizes of DBZ-NLC and PEG-DBZ-NLC were 94.54nm and 70.26nm, respectively, and the encapsulation efficiencis were above 85%.2. HPLC-MS analysis method of DBZ and DSS were established in rat plasma, and the serum concentrations were determined after iv administration of DBZ solution, DBZ-NLC and PEG-DBZ-NLC in rats. The results showed that the half-life of plasma of DBZ solution, DBZ-NLC and PEG-DBZ-NLC were 6.09,29.03,95.47min, and the area under the curve were 132.58,284.52,528.91mg-min·L-1. It demonstrates that PEG-DBZ-NLC prolonges the retention time of DBZ in rat plasma.3. Microdialysis technique was used to investigate the brain targeting propertis of PEG-DBZ-NLC. A HPLC-ECD method was developed and validated for DBZ and DSS in microdialysis samples. The results showed that the DBZ and DSS concentrations in microdialysis solution were all obviously higher following iv PEG-DBZ-NLC than that after iv DBZ-NLC and PEG-DBZ-NLC. Furthermore, the brain target index was more than one for PEG-DBZ-NLC, which showed good brain targeting property. |
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