Chimie des promédicaments, approches non synthétiques pour améliorer la biodisponibilité

Abstract

Prodrugs are pharmacologically inactive substances that require an in vivo transformation to release the active ingredient. This strategy aims to overcome several limitations of conventional active ingredients, such as low solubility, enzymatic degradation, or poor absorption. This thesis focuses on the chemistry of prodrugs, with particular emphasis on non-synthetic approaches used to improve their bioavailability. The main objective of this work is to explore how certain non-synthetic approaches, such as vectorization, the use of endogenous enzymes, or nanotechnologies, can improve the biological availability of prodrugs without resorting to heavy chemical modifications. Through a case study of four clinically used prodrugs (tamoxifen, clopidogrel, capecitabine, and enalapril), an in-depth analysis of enzymatic activation mechanisms and controlled release was carried out. This approach made it possible to demonstrate the therapeutic interest of alternative strategies and to highlight their role in optimizing the effectiveness of treatments. In conclusion, non-synthetic approaches represent a promising avenue in pharmaceutical development, by offering suitable solutions to the challenges of bioavailability while respecting the biological complexity of living systems.