Apolipoproteins adsorption and brain-targeting evaluation of baicalin nanocrystals modified by combination of Tween80 and TPGS.

To help baicalin pass across BBB and improve its targeting in brain, we designed a novel formulation strategy of baicalin nanocrystals that preferentially adsorbing apolipoprotein E (ApoE) and repelling protein adsorption of opsonins. Intravenous baicalin nanocrystals suspensions (BCL-NS) modified by different surfactant were prepared by high-pressure homogenization. The targeting potential of surface-modified BCL-NS with mean particles size of about 250nm was assessed by in vitro protein adsorption studies using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), and further evaluated in vivo pharmacokinetics. The protein adsorption results showed that BCL-NS/TPGS, BCL-NS/TW80 and BCL-NS/TPGS+TW80 adsorbed very high amounts of apolipoproteins (ApoA-I, ApoA-Ⅱ, ApoA-IV, ApoC-III, ApoE, ApoJ) and relative low amounts of opsonins (fibrinogen, immunoglobulin heavy chain gamma, immunoglobulin light chain). The pharmacokinetics results demonstrated the AUC (0-∞) in brain of the BCL-NS/TW80+TPGS was 6.67 times as high as that of the BCL solution, and 2.59 times as high as that of the BCL-NS/TW80. It could be attributed to the most ApoE and Apo J adsorption indicative of strong BBB penetration, and least IgG γ and fibrinogen loading minimizing the risk of hepatic uptake. Combination of TW80 and TPGS can be rational choice of surfactants of baicalin nanocrystals for brain-targeting mediated by ApoE adsorption.