Augmentation de l’absorption intestinale à l’aide de promédicaments se liant aux gangliosides GM1
In order to increase the bioavailability of poorly permeable drugs, a biomimetic approach was investigated. This approach replicated the internalisation of the cholera toxin using GM1 ganglioside receptor on the intestinal cells. The proposed technology was to synthesize a prodrug consisting of a low permeability therapeutic molecule and a GM1-binding peptide. The hypothesis of this work was that the peptide part of the prodrug will enhance the intestinal absorption of the therapeutic molecule and that the complex will be metabolised rapidly after absorption. Prodrugs were synthesized and stability, affinity and permeability tests were developed and performed.  The results of this study demonstrated the possibility of synthesizing prodrugs from a GM1-binding peptide and a drug demonstrating poor bioavailability. Stability, affinity and permeability tests were successfully optimized and implemented. The initial in vitro study highlighted promising binding properties of the peptide and one of the prodrugs. However, stability tests showed partial metabolism of the prodrugs in plasma and instability of the stock solutions. Moreover, results of permeability tests were inconclusive. Future studies will involve the preparation of other prodrugs using the same approach and the investigation of the peptide's internalisation mechanism.
Ganglioside GM1 Absorption Endocytose Prodrug Cholera toxin GM1 ganglioside Affinity Stability Intestinal permeability Bioavailability Endocytosis