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Tyrosine-based rivastigmine-loaded organogels in the treatmant of Alzheimer's disease
Article [Accepted Manuscript]
Is part ofBiomaterials ; vol. 31, no 23
- Université de Montréal. Faculté de pharmacie
Organogels can be prepared by immobilizing an organic phase into a threedimensional network coming from the self-assembly of a low molecular weight gelator molecule. In this work, an injectable subcutaneous organogel system based on safflower oil and a modified-tyrosine organogelator was evaluated in vivo for the delivery of rivastigmine, an acetylcholinesterase (AChE) inhibitor used in the treatment of Alzheimer’s disease. Different implant formulations were injected and the plasmatic drug concentration was assayed for up to 35 days. In parallel, the inhibition of AChE in different brain sections and the biocompatibility of the implants were monitored. The pharmacokinetic profiles were found to be influenced by the gel composition, injected dose and volume of the implant. The sustained delivery of rivastigmine was accompanied by a significant prolonged inhibition of AChE in the hippocampus, a brain structure involved in memory. The implant induced only a minimal to mild chronic inflammation and fibrosis, which was comparable to poly(D,L-lactide-co-glycolide) in situ-forming implants. These findings suggest that tyrosine-based organogels could represent an alternative approach to current formulations for the sustained delivery of cholinesterase inhibitors.
Guillaume Bastiat, François Plourde, Aude Motulsky, Alexandra Furtos, Yvan Dumont, Rémi Quirion, Gregor Fuhrmann, Jean-Christophe Leroux, Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease, Biomaterials, Volume 31, No 23, Août 2010, Pages 6031-6038.