Abstract
Purpose: A novel brain targeting drug delivery system based on OX26 antibody conjugation on PEGylated cationic solid lipid nanoparticles (OX26-PEG-CSLN) was prepared.
Methods: The Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody (OX26-PEG-CSLN) were prepared by emulsion evaporation–solidification at low temperature method. The immune-gold labeled OX26-PEG-CSLN was visualized by transmission electron microscopy. The mean diameter and zeta potential of OX26-PEG-CSLN, PEG-CSLN and CSLN were determined using a Zetasizer. The entrapment efficiency of OX26-PEG-CSLN, PEG-CSLN and CSLN was determined by ultrafiltration centrifugation method. And the solid-state characterization of OX26-PEG-CSLN and CSLN were analyzed by X-ray. Pharmacokinetics studies were conducted by in vivo microdialysis in rat cerebrospinal fluid.
Results: The results showed that the OX26-PEG-CSLN, PEG-CSLN and CSLN had average diameters of 47.68 ± 1.65, 27.20 ± 1.70 and 33.89 ± 5.74 nm, Zeta potentials of −0.533 ± 0.115 mV, 11.200 ± 0.500 mV and 11.080 ± 1.170 mV and entrapment efficiencies of 83.03 ± 0.01%, 92.90 ± 3.50% and 97.83 ± 0.19%, respectively. In the pharmacokinetics studies, the AUC value of OX26-PEG-CSLN was11.08-fold higher than that of the Baicalin solution (SOL) (p < 0.01), and 1.12-fold higher than that of the CSLN (p > 0.05); the Cmax value of OX26-PEG-CSLN was 7.88-fold higher than that of SOL (p < 0.01) and 1.12-fold (p < 0.01) higher than that of the CSLN, respectively.
Conclusion: These results demonstrated OX26-PEG-CSLN could be a promising carrier to deliver drugs across the BBB for the treatment of brain diseases.
Declaration of interest
The authors report no conflicts of interest in this work. This study was financial supported by the National Natural Science Foundation of China (81001645), Program for New Century Excellent Talents in University (NCET-12-1068), Tianjin Natural Science Foundation (12JCYBJC18700), the National Key Technology Research and Development Program of China (2012ZX09304007).