The following steps yielded 500 µl of nanoparticle solution which is sufficient to inject 100 µl/tumor in 5 mice, and the actual amounts were scaled up proportionally according to the number of mice used.
Mouse time-activity curves were scaled to human using the organ-weight scaling method and published kidney compartment sizes [18].
A major reason for using surface area in the first instance stems from the early data of Freireich and colleagues (Freireich et al, 1966), who showed that maximum tolerated doses of cytotoxic drugs where often the same in different species, ranging from mice to humans, when doses were scaled according to surface area.
Cell membrane transport parameters were scaled up from mice to humans by assuming that the contact surface between interstitial and intracellular mediums was proportional to the cell volume such that: where p stands for,,, or, and for the normal brain or tumor intracellular volume.
Fly genes were scaled to 1.2 kb and values were extracted from published data sets, mouse genes were scaled to 30 kb.
Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat.
In contrast, peak data from Mbnl1 ΔE3/ΔE3 and Mbnl1 ΔE3/ΔE3/mice3 ΔE2 must, must be scaled by 1.46 and 1.88 factors (respectively), in order to become superimposable with those from wild type animals (not shown).
To examine whether our DNA vaccine had sufficient potency to be scaled from mouse to human, we examined the delivery of our DNA vaccine using the Inovio Elgen100 device for the first time in the clinic.
At this time point, mice were scored on a scale of "0" to "4" for percent body coverage of hair "0" = complete alopecia; "1" = <25% hair coverage; "2" = 25 50% hair coverage; "3" = 50 75% hair coverage; "4" = normal hair density and full hair coverage.
General physical activity of mice was scored on an arbitrary scale of 1 4, with 4 being normal activity and 1 being moribund (euthanized subsequently).
