Accueil du site > Equipes > Vecteurs colloïdaux et transport tissulaire (B. Verrier) > Colloidal vectors and tissue transport (B Verrier)
Background : The use of biodegradable nanoparticulate systems to deliver therapeutic agents provides many advantages, either in terms of drug stability, protection from degradations or limitations of their side effects. However, the development of this approach faces a major obstacle : the efficiency of migration of nanoparticles through the various barriers and extracellular tissue before reaching their target cells. The difficulties to overcome this obstacle are related to both the lack of three-dimensional immuno-competent models, able to mimic in vivo conditions and the difficulty of designing "intelligent" nanoparticles able to cross the various barriers without degradation of the vectorized drug.
Also, since 2005 we are focused on the development of biodegradable nanoparticles based on poly (D, L-lactic acid) (PLA) and the targeting of mono or multilayered tissues (skin and mucosae). By analogy with a viral particle, we design multifunctional nanoparticles covered in surface with one or more viral proteins as well as immunostimulatory molecules such as ligands of Toll-like receptors (TLR) or Nods. Using the synthesis process of nanoprecipitation, we can encapsulate various hydrophobic molecules such as fluorophores (Coumarin 6, BODIPY CellTrace) or antiretrovirals (Efavirenz), and we are also able to develop micelles based on block copolymers. These properties enable us to track the fate of these nanoparticles, both in 2-D models (co-culture Caco-2 cells and M), ex vivo (intestine) or in vivo after cutaneous or transcutaneous administration in non-human primates or humans, and in a whole animal model, the zebrafish.
Objectives : Our research project builds on our expertise to dissect the mechanisms of migration of PLA nanoparticles in tissues mono and multilayered to identify correlates between the ability to migrate, therapeutic efficacy and physico-chemical properties of nanoparticles (size, charge). These observations allow us to define “intelligent” nanoparticles and micelles (colloid) able to migrate efficiently in a structured mesh and to go through a mono-or multilayered tissue. Several therapeutic applications are evaluated with the help of our collaborative networks, as FIV or HIV-1.
Themes of the laboratory :
Transport through a single- or multi- layered tissue
Transport through the extracellular matrix,
Institut de Biologie et Chimie des Protéines
FRE3310 - DyHTIT
7, passage du Vercors
69 367 Lyon cedex 07
Phone : +33(0)4 72 72 26 36
Fax : +33(0)4 72 72 26 01
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