Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer's disease.
Organogels can be prepared by immobilizing an organic phase into a three-dimensional 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.
Bastiat
Guillaume
G
Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada.
Plourde
François
F
Motulsky
Aude
A
Furtos
Alexandra
A
Dumont
Yvan
Y
Quirion
Rémi
R
Fuhrmann
Gregor
G
Leroux
Jean-Christophe
JC
D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002853:Chromatography, Liquid; D005782:Gels; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D048448:Phenylcarbamates / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000068836:Rivastigmine; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000737:chemistry*
D002800:Cholinesterase Inhibitors; D005782:Gels; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D014443:Tyrosine; D000068836:Rivastigmine
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