Drug delivery and mathematical modeling: an historical perspective

It is probably not well known that 4000 years BC Sumerians were able to prepare many medicaments and that the same were used to do Assyrians, Babylonians and Egyptians 3000 years BC. Interestingly, the idea that illness is a sort of divine punishment and healing is the consequent purication, was born in that time and this view heavily aected the western world up to the modern age. If Hippocrates and Galenus, the two most famous witnesses of the Greek and Roman medicinal world, started detaching from this viewpoint, the scientic darkness permeating Europe after the end of the Roman Empire rearmed this way of conceiving illness. Only in the 9th -13th centuries, thanks to the golden age of the Arab Science, something changed and, undoubtedly, represented the basis for the big cultural and scientic revolution represented by Renaissance. Interestingly, in the rst half of the 16th century, Paracelsus, with a very modern vision, conceived human body as a chemical laboratory. However, it is only at the end of the 19th century that, under a rigorous experimental Galilean approach, the real origins of many diseases were discovered. Consequently, this can be considered as the beginning of the modern pharmaceutics whose task is to optimize and improve the clinical eects of drugs. Since then, drug delivery has developed and after the 2nd world war it entered in its modern age with the realization of the rst controlled release system (1952). Notably, the rst example of mathematical modelling trying to simulate drug release from a delivery system appeared 9 years later (1961) and the clear armation of mathematical modelling in the biopharmaceutical eld took place in the last twenty years of the 20th century thanks to valuable researchers such as Peppas and Langer. The third millennium opens with new important challenges for delivery systems designing and mathematical modelling such as the overcoming of biological barriers. This means stopping focusing only on the mathematical modelling of drug release but also considering adsorption, distribution and elimination processes that rule drug fate in vivo. The theoretical bridge joining these two aspects of mathematical modelling could be the ancient, but evergreen, mass balance stating that the administered dose does not disappears but it spreads among tissues before complete elimination/metabolization. In so doing, the idea of Paracelsus about human body has been denitely accepted