INSERM U1008: Advanced Drug Delivery Systems

Numerous drug candidates fail to show in vivo efficacy. This can be attributed to their physicochemical properties and/or pharmacokinetics/pharmacodynamics, in particular poor aqueous solubility, poor permeability across biological barriers, rapid drug elimination out of the living body and/or narrow therapeutic windows. Even if the substance exhibits an ideal chemical structure allowing for optimal therapeutic effects, the therapy fails if the drug cannot reach its site of action in the human body.

Our aim is to overcome these restrictions and to develop novel types of advanced drug delivery systems and biomaterials allowing for an accurate control of the resulting drug release kinetics during periods ranging from a few minutes up to several years. Thus, the drug can effectively be protected in the human body and potentially administered directly at its site of action. We work on different types of systems, in particular :

  • Coated pellets which are orally administered and allow for site specific drug delivery to the colon. This is of major benefit for the treatment of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis
  • Biodegradable microparticles for parenteral administration, especially for the treatment of brain diseases (e.g., cancer and neurodegenerative disorders)
  • Lipid implants for the controlled delivery of fragile protein drugs (e.g., growth factors)
  • Drug eluting stents with improved biocompatibility
  • Implants releasing antibiotics and anesthetics in a time controlled manner for dental surgery
  • Scaffolds releasing incorporated drugs at a pre-determined rate for bone substitution in facial surgery.

We prepare the different types of advanced drug delivery systems and biomaterials using a broad range of techniques, for instance via direct compression of drug-polymer blends, fluidized bed coating, extrusion, and freeze drying. The devices are thoroughly characterized in vitro with a large variety of physicochemical and biological methods (e.g., in vitro drug release measurements, differential scanning calorimetry, size exclusion chromatography, mechanical analysis, cell culture tests, biocompatibility and bioerosion studies). Furthermore, the pharmacokinetics and pharmacodynamics of the drugs are determined in vivo (animal models and clinical trials).

Based on these experimental results, novel mathematical theories are developed allowing for the elucidation of the underlying drug release mechanisms and for the quantitative prediction of the effects of formulation and processing parameters on the resulting drug release kinetics. Thus, the optimization of the novel drug delivery systems and biomaterials can be facilitated. Furthermore, we establish in vitro – in vivo correlations, in particular with respect to the drug release kinetics. This allows to reduce the number of required animal studies and to improve the safety of the novel pharmaco-therapies.

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