NT1-O12B, an endogenous chemical and a neurotransmitter-derived lipidoid (NT-lipidoid), is an effective carrier for enhanced brain delivery of several blood-brain barrier (BBB)-impermeable cargos. Doping NT1-O12B into BBB-impermeable lipid nanoparticles (LNPs) gives the LNPs the ability to cross the BBB. NT-lipidoids formulation not only facilitate cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination[1].
NT1-O12B indicates a lipidoid containing a tryptamine head group and a hydrophobic tail group containing 12 carbon atoms[1].
It encapsulates AmB in pure NT1-lipidoids (namely NT1-O12B, NT1-O14B, NT1-O16B, and NT1-O18B) using a procedure similar to the DiR encapsulation. NT1-O12B is the dopant for enhanced brain delivery because it shows the highest DiR fluorescence intensity among all NT-lipidoids. Doping NT1-O12B to the BBB-impermeable lipidoid PBA-Q76-O16B resulted in an AmB formulation that could cross BBB. Using this approach, the AmB concentration in the brain tissue reached as high as 300 ng/g (AmB/tissue) with a delivery efficiency of about 0.135% of injected dose after 24 hours of intravenous injection with AmB (5 mg/kg)[1].
[1]. Ma F, et al. Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection. Sci Adv. 2020;6(30):eabb4429. Published 2020 Jul 24.