In Silico Track to Reveal a Translational Potential of Porphyrin-C60 Nanoparticles in the Ischemic Stroke Related Preclinical Studies

Author(s): Valentin Fursov, Daria Zinchenko, Dmitriy Kuznetsov.

The In Silico study on neuropharmacokinetiks of some novel porphyrin-fullerene based 25Mg2+ - nanocarriers was performed with an aim to optimize the preclinical research path required for both prevention and correction of brain ischemic stroke related metabolic disorders such as ATP deplete and its direct consequences. Thus, the local brain tissue hypoxia scenario is in a focus of this novel analytical approach suitable for prediction of some parameters of the 25Mg – magnetic isotope effect promoted antihypoxic activities as long as they relate upon delivery, distribution and intralization of the low toxic/amphiphilic Mg2+ – releasing nanoparticles of PMC16 type. This is the first report ever on mathematical model applied to predict and to prove a mere phenomenon of the “cellular pump” keeping the constant traffic of PMC16 particles towards a brain hypoxia area even when/if lowest concentration of pharmacophore were the case. Two versions of mathematical model were proposed in a present study: (a) a basic two-compartment model to describe a mechanism of the nanopharmacophore targeted delivery towards the brain ischemia area, and (b) an advanced five-compartment model, verified and supported by some specific experimental data on PMC16 distribution (CZE) in organs/tissues. A novel procedure of the capillary zone electrophoresys (CZE) suitable for a reliable validation of the In Silico – predicted PMC16 pharmacofore pharmacokinetic patterns, has been proposed and discussed For experimental verifications of the In Silico platform proposed, a combination of (a) the rat brain occlusion – promoted ischemic stroke model and (b) the capillary zone electrophoretic (CZE) quantification of PMC16-RX nanoparticles in cytosol fractions isolated from intact / penumbra / stroke brain areas, has been employed. From a practical point of view, a novel In Silico systematic directory proposed might indicate a perspective for clear and essentially simplified plan making required to design an optimized protocol suitable for the [25Mg2+]4PMC16 – related preclinical research program.