Figure 5
From: Pharmacokinetics, biodistribution and toxicology of novel cell-penetrating peptides
L-S-CPP crossed the blood–brain barrier, as assessed with in situ cerebral perfusion (ISCP). (A) The brain uptake coefficient (Clup; µl s−1 g−1) of 3H-L-S-CPP was calculated as Vbrain/T, where T is the time perfusion (60 s). Injected concentrations were: 0.08, 0.16 and 0.32 µg/ml, corresponding to doses per mice of 0.2, 0.4 and 0.8 µg. The rate of entry of 3H-L-S-CP in the brain did not decrease with higher concentrations, consistent with the absence of a saturable transport mechanism. (B) The pmol/g of 3H-L-S-CPP in the brain were estimated from the dpm/g (L-S-CPP) and the specific activity and showed a linear increase (r2 = 0.88; p < 0.0001), in accordance with free diffusion across the BBB. (C) Comparison of the proportion of 3H-L-S-CPP found in the vascular or extravascular fractions of the brain, showing a fast distribution into the brain parenchyma. Data are represented with the mean of N = 4–7 ± SEM. Statistical analyses were performed by a One-Way ANOVA parametric test followed by a Tukey post-hoc test (*p < 0.01) or a Welch ANOVA parametric test followed by a Dunnett’s post-hoc test (¤p < 0.05; ¤¤¤p < 0.001). Clup brain uptake coefficient, S-CPP Shuttle cell-penetrating peptides.
