Intranasal thermosensitive gel for brain-targeted delivery of α-Cyperone-loaded solid lipid nanoparticles

To develop and evaluate α-Cyperone (α-Cy)-loaded solid lipid nanoparticles (SLNs) incorporated into a thermosensitive in situ gel for enhanced intranasal delivery and improved neuroprotective efficacy.

α-Cy-SLN was prepared using high-pressure homogenization followed by freeze-drying. The formulation was optimized using a Box-Behnken Design, assessing the effects of lipid-to-surfactant ratio on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency (EE). The optimized SLNs were characterized for physicochemical properties, in vitro drug release, and brain cell penetration.

The optimized α-Cy-SLNs (Run 5) exhibited a mean particle size of 279.5 ± 0.06 nm, PDI of 0.203 ± 0.24, zeta potential of -23.1 ± 2.38 mV, EE of 70.0 ± 2.21%, and product yield of 72.58 ± 1.24%. In vitro studies demonstrated a sustained release of α-Cy from the SLNs, indicating the formulation's potential for prolonged drug delivery. Incorporation into the thermosensitive in situ gel further supported controlled release and enhanced bioavailability.

The developed α-Cy-SLN in situ gel formulation offers a promising strategy for intranasal delivery, improving α-Cy bioavailability and therapeutic potential for neuroprotection in Alzheimer's disease.