Table 1. Transwell Inhibition Experimentsa.
percent ± SEM of BBB-permeability remaining
in the presence of competitor |
|||
---|---|---|---|
nanoconjugate | JPH203 ± SEM | Aβ1–40 | AP2 ± SEM |
P/LLL | 111 ± 3 (0.213, ns) | - | 80 ± 2 (0.045, *) |
P/LLL/D3 | 80 ± 2 (0.0009, ***) | 30 ± 4 (0.0005, ***) | 66 ± 4 (0.0005, ***) |
P/LLL/AP2 | 58 ± 5 (0.016, *) | 41 ± 8 (0.007, **) | - |
Permeability competition experiments using the in vitro Transwell model of the BBB. Permeation through the model was measured by fluorescence intensity in the target compartment. Competition is indicated by the relative fluorescence decrease in the presence of the tested compound. (1) D3-nanoconjugate inhibition by AP2. (2) AP2- and D3-nanoconjugate inhibition by Aβ.16,35 (3) AP2- and D3-conjugate inhibition by inhibition with the LAT-1 specific inhibitor JPH203.73 (4) P/LLL(40%) by marginal inhibition with AP2. P/LLL(40%), the nanoconjugate platform, served as a control. *p < 0.05, **p < 0.01, ***p < 0.001, Student’s t test comparing compounds in the presence and absence of inhibitor. The mode of inhibition, competitive or noncompetitive, was not determined.