Table 1.
Overview of the characteristics of the CPPs selected for the investigation of their BBB transport properties.
Fig 1.
Results of the multiple time regression analysis experiment of the five CPP using the linear model.
Table 2.
Overview of the quantitative influx characteristics (± 65% confidence limits) of the five investigated CPPs based on linear and biphasic modeling of the multiple time regression analysis data.
Fig 2.
Result of the multiple time regression analysis experiment of SynB3, Tat 47–57 and dermorphin using the biphasic model.
The ratio of the brain-to-serum activity is plotted versus the exposure time and fitted using the biphasic model.
Fig 3.
Evaluation of the BBB permeability after injection of pVEC and used brain influx mechanism of pVEC, TP10 and SynB3.
(A) Evaluation of the BBB permeability after IV injection of pVEC: ratio of brain-to-serum radioactivity versus exposure time of radioiodinated BSA with (purple squares) and without (black dots) an excess dose of pVEC (20 μg). (B-D) Evaluation of the saturability of the BBB influx mechanism of pVEC, TP10 and SynB3, respectively: ratio of brain-to-serum radioactivity versus exposure time with (purple squares) and without (black dots) an excess dose of the CPP (10 μg). Data are fitted using the linear Gjedde-Patlak model, except for the data of SynB3, which are fitted using the biphasic model.
Fig 4.
Regional variations in brain influx of pVEC, TP10, SynB3, dermorphin and radioiodinated BSA.
The data of pVEC, TP10 and radioiodinated BSA are fitted using the linear Gjedde-Patlak model; the data of SynB3 and dermorphin are fitted using the biphasic model. Grey = whole brain, yellow = frontal cortex, purple = occipital + parietal cortex, light blue = cerebellum, dark blue = striatum, brown = thalamus + hypothalamus, orange = pons medulla, green = hippocampus and red = midbrain.
Table 3.
Kin and Vi values of the whole brain and eight brain regions of pVEC (between brackets the 65% confidence interval is indicated).
Fig 5.
Relative tissue distribution of the radiolabeled CPPs and the controls dermorphin and radioiodinated BSA 15 min post IV injection expressed as the percentage of the injected dose (± SEM, n = 2).
From the left to the right: brain (light blue), spleen (dark blue), kidneys (purple), lungs (red), heart (orange), liver (yellow) and serum (light green).
Table 4.
Overview of the in vitro metabolic stability results of the five investigated CPPs.
Fig 6.
Schematic overview of the relationship between cell-penetrating and BBB-penetrating properties of the five investigated CPPs.
The thickness of the arrows indicates the extent of influx and/or efflux.