Department of Pharmaceutical Technology

Nanomedicine an Original Concept to Treat Severe Diseases

Nucleoside analogues display significant anticancer or antiviral activity by interfering with DNA synthesis. However, there are some serious restrictions to their use, including their relatively poor intracellular diffusion, rapid metabolism and the induction of resistance. We have discovered that the linkage of nucleoside analogues to squalene, leads to amphiphilic molecules which self-organize in water as nanoassemblies of 100-300nm, irrespective of the nucleoside analogue used. The squalenoyl gemcitabine exhibited superior anticancer activity In vitro in human cancer cells and gemcitabine-resistant murine leukemia cells, and In vivo in experimental leukemia both after intravenous and oral administration. The squalenoylation of other antiretroviral nucleosides also led to more potent drugs when tested in primary cultures of HIV-infected lymphocytes. Thus the squalenoylation is an original technology platform to generate more potent anticancer and antiviral nanomedicines.

patrick.couvreur@u-psud.fr

Department of Toxicology

Preclinical and Clinical Safety Evaluation of the Biotherapeutics

The aim of this presentation is to provide an overview of how the safety of biotherapeutics such as monoclonal antibodies or cytokines is evaluated at the preclinical level. Extrapolation of results from animals to humans will be addressed using examples from clinical situation such as the Tegenero accident.

marc.pallardy@u-psud.fr

Department of Microbiology

Clostridium Difficile, a Major Enteropathogen, Virulence Factors and Therapeutics Strategies

anne.collignon@u-psud.fr

Department of Pharmaceutical Technology

Modifying Surface Properties can Turn a Foreign Body into a Smart Nanoparticle

When injected intravenously, particles smaller than 5 µm are able to circulate, but rapidly taken up by macrophages. Materials are foreign bodies and isolated from living tissues by non-specific protection mechanisms. These are initiated by proteins adsorption and changes of conformation, resulting in activation of the complement system and uptake by phagocytes. Interactions between nanoparticles and biological systems are surface-dependent phenomenons. Oligo- and polysaccharides are involved in masking, recognition and signalization phenomenons of bacteria and viruses. A biomimetic strategy can be covering the surface of nanoparticles with bound polysaccharides. Complement activation, adsorption of blood proteins and circulation time in the bloodstream strongly depend on the type, structure and length of the polysaccharidic coating.

denis.labarre@u-psud.fr
christine.vauthier@u-psud.fr

Department of Pharmaceutical Technology

The Use of Colloidial Drug Delivery Systems to Improve the Therapeutic Index of Drugs

Drug carriers are designed to modify drug distribution within the organism. Colloidal drug carriers, which include liposomes and nanoparticles, are small enough to be administered by a general route and to carry an active product to its site of action. Two systems developed in our laboratory will be described:
1. Long-circulating nanocapsules to provide circulating reservoirs of a drug in the blood and to convey a drug to accessible site outside the vasculature, in particular when the endothelial barrier is leaky as in the case of infection, inflammation and in the vasculature supplying solid tumours.
2. Lipid-based colloids to reduce the toxicity and to improve the efficacy of Amphotericin B (AMB), a broad-spectrum antifungal and antiparasitic agent.

gillian.barratt@u-psud.fr

Department of Pharmaceutical Technology

Nanotechnologies for Nucleic Acid Delivery

elias.fattal@u-psud.fr