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

Area of Science:

• Nanotechnology
• Pharmaceutics
• Neuroscience

Background:

• Alzheimer's disease (AD) poses a significant challenge, necessitating novel drug delivery systems for effective neuroprotection.
• Intranasal delivery offers a direct route to the brain, bypassing the blood-brain barrier.
• Alpha-Cyperone (α-Cy) has shown potential neuroprotective properties, but its delivery is limited.

Purpose of the Study:

• To develop and evaluate α-Cyperone (α-Cy)-loaded solid lipid nanoparticles (SLNs).
• To incorporate the optimized SLNs into a thermosensitive in situ gel for enhanced intranasal delivery.
• To assess the neuroprotective efficacy of the developed formulation.

Main Methods:

• α-Cy-SLNs were prepared using high-pressure homogenization and freeze-drying.
• Formulation optimization was performed using Box-Behnken Design, evaluating key parameters like particle size, PDI, zeta potential, and entrapment efficiency (EE).
• Physicochemical properties, in vitro drug release, and brain cell penetration were characterized.

Main Results:

• Optimized α-Cy-SLNs (Run 5) showed a particle size of 279.5 nm, PDI of 0.203, zeta potential of -23.1 mV, and EE of 70.0%.
• In vitro studies confirmed sustained α-Cy release from SLNs, indicating potential for prolonged drug delivery.
• Incorporation into the thermosensitive in situ gel further supported controlled release and enhanced bioavailability.

Conclusions:

• The developed α-Cy-SLN in situ gel formulation is a promising strategy for intranasal delivery.
• This approach enhances α-Cy bioavailability and its therapeutic potential for neuroprotection in Alzheimer's disease.