AmyloLipid Nanovesicles: A self-assembled lipid-modified starch hybrid system constructed for direct nose-to-brain delivery of curcumin

Abstract

AmyloLipid nanovesicles (ALNs) are new lipid-modified starch complex nanoparticles developed and presented as nanocarriers of curcumin for targeting the CNS via the intranasal route. Curcumin has been indicated as a promising active agent with a variety of pharmacological activities, including a potential ability to treat brain tumors, traumatic brain injury, and CNS disorders, such as Alzheimer's disease, as it may inhibit amyloid-β-protein (Aβ) aggregation and Aβ-induced inflammation. Although curcumin has a tremendous potential as a therapeutic agent for CNS disorders, its low bioavailability and its rapid total body clearance reduce any chance for therapeutic levels to reach the brain. By using an optimized (2% crosslinked starch) curcumin-loaded ALNs, which was fabricated from a microemulsion as a precursor, an average of 141.5 ± 55.9 ng/g brain levels and 11.9 ± 12.0 ng/ml plasma concentrations were detected, one hour following intranasal administration of 160 μg/kg dose of curcumin. In comparison, 1 h after IV administration of the same dose, no CUR was detected in the brain and the mean plasma level was approximately one half of the level monitored after intranasal ALNs, i.e., 7.25 ± 0.20 ng/ml. It has been clearly demonstrated, therefore, that a well-designed ALN formulation proved itself as a promising carrier for intranasal delivery and brain targeting of curcumin.

Keywords: Amylolipid nanovesicles; Brain targeting; Curcumin; Intranasal drug delivery; Lipid-starch hybrid; Modified starch.