European partners to develop nanocarriers for inflammatory bowel
20 April 2011
French research organisation CEA-Leti has announced a new
project to develop nano-pharmaceuticals to improve the treatment of
inflammatory bowel diseases.
The Delivering Nano-pharmaceuticals through Biological Barriers
project (BIBA), involves eight partners in France, Germany, Spain
and Switzerland. The project is coordinated by CEA-Leti as part of
its research program on organic nanocarriers and delivery systems
for clinical applications like molecular imaging and drug delivery.
The three-year study is designed to develop an anti-inflammatory
corticoid and/or an immunosuppressant encapsulated within a
biodegradable nanocarrier for improved treatment of IBD and reduced
side effects. Industry supervision of the preclinical proof of
concept will enhance quality control to guaranty a faster regulatory
application after the project.
Inflammatory bowel disease (IBD) includes Crohn’s disease (CD)
and ulcerative colitis (UC). Medical treatment of IBD is mostly
based on the use of corticosteroid to induce remission and of an
immunosuppressant to prevent relapses. But these approaches are
inefficient in more than 70% of patients with CD, and 20% of the
patients with UC who ultimately require surgery for control of the
disease. Corticosteroids like prednisolone can induce remission in a
high proportion (60-80%) of patients.
However, the required doses of steroids cannot be administered
long-time due to adverse events. BIBA will investigate local
delivery of encapsulated corticosteroids and immunosuppressants
using two types of organic biodegradable nanocarriers to prevent
side effects. Passive targeting of nano-delivery systems in inflamed
tissues exploiting the so-called enhanced permeability and retention
(EPR) effect is expected to increase the local concentration of
corticoïds in inflamed areas.
One model of corticoid, budesonide, and one model of
immunosuppressant, cyclosporine, will be separately encapsulated in
three dosage forms — oral, colonic, and intravenous — to maximise
the delivery of anti-inflammatory drugs through the gastrointestinal
tract, with two nanocarriers: lipid “baby bubbles” (Lipidots) and
poly(lactic-co-glycolic acid) (PLGA) particles. In vitro experiments
will be performed on a lab model of healthy and pathological
epithelium to screen the most relevant nano-pharmaceuticals.
Formulations will then be evaluated in vivo in appropriate rodent
colitis models. Animal models allow both the examination of
inflammatory processes (both early and late events) as well as the
evaluation of new therapeutic modalities. Non-invasive magnetic
resonance imaging (MRI) and optical fluorescence in combination with
histological analysis will be used to monitor the effect of the
therapy on the inflamed mucosa.
The BIBA study is funded by the European programme ERANET
EuroNanoMed. CEA-Leti’s partners in the project include:
- Helmholtz-Institute for Pharmaceutical Research Saarland,
- PHAST Gesellschaft für Pharmazeutische Qualitätstandards
mbH, Homburg, Germany;
- Institut Albert Bonniot, INSERM-UJF U823, Grenoble, France;
- Instituto de Investigación Sanitaria La Paz, Madrid;
- Institut Investigacions Biomèdiques August Pi i Sunyer,
- Institute of Anatomy, University of Zurich.