Académie royale de Médecine de Belgique


Résumé de Véronique Préat




par Mme V. PRÉAT (U.C.L.), invitée.         


Nanotechnologies are significantly impacting the development of both therapeutic and diagnostic agents.  Nanomedicines are nanometer scale complex systems consisting of at least two components one of which is the active ingredient.  The other components are lipids or polymers that are conjugated to the drug or that encapsulate the drug in liposomes or nanoparticles.  The nanomedicines can i) serve as a carrier to solubilise poorly soluble drugs or protect fragile drugs and ii) modify the pharmacokinetics of the drug to decrease its toxicity and/or increase its efficacy.

The concept of nanomedicine has evolved with time.  The first generation consisted in lipid-based liposomes. They are still marketed to decrease the side effects of the encapsulated drug (e.g. doxorubicin or amphotericin B) but do not display and optimal phamacokinectics due to high uptake by the reticuloendothelial system.  The second generation was PEGylated at the surface to provide stealthiness and to extend the drug half-life, (e.g doxyl for cancer treatment).  The nanomedicines are passively targeted to the tumor by the so called enhanced permeation retention effect (EPR) linked to the fenestration of endothelial cells in tumor vessels. The next progress was to graft at the nanoparticle surface a ligand that specifically binds to a cell or a tissue to achieve targeted drug delivery.  These systems are currently in preclinical or early clinical studies, mainly for cancer treatment.  They are actively targeted by ligands that target the tumor endothelium and/or the cancer cells.  Finally, the future nanomedicines are the theranostic nanoparticles which can be exploited both for diagnosis and treatment of a disease.  Clinical application of this fourth generation of nanoparticles is largely unexplored.  The toxicity of the nanoparticles is also a critical issue that will be discussed.