NT1-O12B, an endogenous neurotransmitter-derived lipidoid (NT-lipidoid), serves as a highly efficient carrier for enhancing the transportation of various blood-brain barrier (BBB)-impermeable cargos to the brain. Incorporating NT1-O12B into BBB-impermeable lipid nanoparticles (LNPs) enables these LNPs to effectively traverse the BBB. In addition to enabling cargo passage through the BBB, NT-lipidoid formulations facilitate efficient delivery of the cargo into neuronal cells for purposes such as 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].

The process encapsulates Amphotericin B (AmB) utilizing NT1-lipidoids—specifically NT1-O12B, NT1-O14B, NT1-O16B, and NT1-O18B following a method akin to DiR encapsulation. Among these, NT1-O12B serves as an effective dopant for brain delivery, demonstrating the highest DiR fluorescence intensity compared to the others. Integrating NT1-O12B with the blood-brain barrier (BBB)-impermeable lipidoid PBA-Q76-O16B produces an AmB formulation capable of crossing the BBB. This technique significantly enhances AmB presence in brain tissue, reaching concentrations up to 300 ng/g (AmB/tissue) and achieving a delivery efficiency of approximately 0.135% of the injected dose 24 hours post intravenous administration of AmB (5 mg/kg)[1].