Improving the Effectiveness of Gene Electrotransfer Administration Protocol by Mathematical Model Investigation

The effectiveness of a pharmacological treatment is in the first instance determined by the adopted therapeutic agents and their correct delivery. However, when the treatment methodology increases its complexity, all the different steps of the full procedure acquire a strong influence on the final results, sometimes pre-clinical laboratory experiments in vivo for the assessment of all the parameters influencing the procedure is anti-economical and/or unpractical. The possibility of an extensive simulation in silico represents, in theory, a very interesting and effective alternative, allowing the detailed exploration of the effects related to the different parameters applied, influencing the final result of a successful drug delivery. In our study, the use of a simulation model for in vivo gene electrotransfer, based on pre-treatment by hyaluronidase and injection of a plasmid vector, has been considered. A large range of different parameters has been investigated, focusing of the most promising areas by an iterative optimization procedure. Our studies give rise to useful indications for the set-up of a full efficacious procedure to apply in gene electrotransfer protocols.