Using the 'dispersion-retention-formulation method' to estimate clinical and preclinical dosage limits for interstitial nanomedicines or agents

We propose the “DRF method” for estimating dosage limits for interstitially administered therapeutic or diagnostic nanomedicines or agents from three characteristic parameters that can be experimentally determined from in vivo data. These are: (i) the dispersion of the injected fluid around the injection site; (ii) the retention of the injected fluid at the injection site; and (iii) the formulation characteristics of the fluid with respect to local and systemic tolerability. We present formulae that allow dose-limit estimates to be made for any preclinical model, as well as for clinical studies. We illustrate the DRF method for the case of iron-oxide-based magnetic fluids, with reference to the published dose limits of regulatory-body-approved magnetic nanoparticles for MRI contrast enhancement, sentinel node detection, iron replacement therapy, and magnetic thermoablation.