Patrick Couvreur, member of the Academy of Sciences, is an Emeritus Professor of Pharmacy at Paris-Saclay University. He is an internationally recognized scientist in nanomedicine. He co-founded three start-up companies (one of them entering the stock market) and developed an anticancer nanomedicine until end of phase III clinical trial. He is also member of the Academies of Technologies, Medicine and Pharmacy in France and foreign member of two of the three US National Academies (Engineering and Medicine).
Abstract – Advanced nanomedicines and drug delivery
The clinical use and efficacy of conventional chemotherapeutics is hampered by the following limitations: (i) drug resistance at the tissue level due to physiological barriers (non-cellular based mechanisms), (ii) drug resistance at the cellular level (cellular mechanisms), and (iii) non-specific distribution, biotransformation and rapid clearance of the drugs in the body. Nanomedicines (ie., drug loaded onto nanocarriers) may overcome some of these limitations. The presentation will show that before entering into clinical trials, the discovery of advanced nanomedicines rests on four scientific pillars: chemistry, physics, cellular and molecular biology as well as, experimental pharmacology. This will be illustrated by the following nanomedicine platforms with the demonstration that interdisciplinarity is the basis for scientific and technological successes:
- The design of biodegradable doxorubicin-loaded polyalkylcyanoacrylate nanoparticles for the treatment of the multidrug resistant hepatocarcinoma (a nanomedicine with phase III clinical trials ended).
- The construction of nanoparticles made of metal oxide frameworks (NanoMOFs), a highly hyperporous material obtained by the complexation of iron oxide clusters with diacids. The nanopores of this material may be finely tuned to the molecular dimension of the drug molecule to be encapsulated.
- The “squalenoylation, a technology that takes advantage of the squalene’s dynamically folded molecular conformation, to link this natural and biocompatible lipid with anticancer drug molecules to achieve the spontaneous formation of nanoassemblies (100–300 nm) in water, without the aid of surfactants. Surprisingly, these squalene-based nanoparticles are using the circulating endogenous LDL as “indirect” carriers for targeting cancer cells with high expression of the LDL receptors. The application of the “squalenoylation” concept for the treatment of brain ischemia and spinal cord injury will be discussed, too. And it will be shown that the linkage of squalene to leu-enkephalin can confer to the targeted neuropeptide a significant anti-hyperalgesic effect, devoted of the morphine side effects (ie., addiction, tolerance and resiratory depression). The possibility to use other terpenes (natural or synthetic) than squalene to design nanoparticles for the treatment of cancer will be discussed, too.
The design of “multidrug” nanoparticles, combining in the same nanodevice chemotherapy and imaging properties (ie., “nanotheranostics”) or various drugs with complementary biological targets will be also examined.
Finally, it will be shown that the construction of nanodevices sensitive to endogenous (ie., pH, ionic strenght, enzymes etc.) or exogenous (ie., magnetic or electric field, light, ultrasounds etc.) stimuli may allow the spatio-temporal controlled delivery of drugs and overcome resistance to current treatments.