WORKS BEST WITHOUT A DEVIATED SEPTUM –
Nov. 12, 2021 – The scientists began by working with GLP-2, a neuropeptide that has shown anti-depressant effects even in treatment-resistant depression. Considering many drugs entering the body lose their therapeutic effectiveness due to endosomal degradation within the cells, the scientists added a peptide-derived sequence to GLP-2, known as a penetration accelerating sequence (PAS), to help evade this degradation. They also enhanced the permeability of the drug to the respiratory epithelium by the addition of another membrane-permeability promoting peptide-derived sequence called cell penetrating peptides (CPP). They then proceeded to test this modified drug in the mouse model of depression.
Their results, detailed in the Journal of Controlled Release, showed that GLP-2 uptake into the respiratory epithelial cells were enhanced owing to the presence of the CPP. GLP-2 endosomal escape was also enhanced by PAS. This double-modification allowed the effective nose-to-brain delivery of GLP-2. Interestingly, the researchers found that the modified IDDS achieved therapeutic effectiveness in 20 minutes, similar to ICV administration. However, IV administration did not demonstrate the intended effect.
“We hope that our results can be replicated in humans in the near future,“ concluded lead author Dr Tomomi Akit. “Our study possibly paves the way for futuristic brain delivery applications like nanobiotechnology and adult genetic engineering.”
