Optimization of artemether-loaded NLC for intranasal delivery using central composite design

Area of Science:

• Nanotechnology
• Pharmaceutics
• Drug Delivery

Background:

• Artemether is a crucial antimalarial drug.
• Intranasal delivery offers a potential route for direct nose-to-brain drug transport.
• Optimizing drug carriers is essential for effective intranasal drug delivery.

Purpose of the Study:

• To optimize artemether-loaded nanostructured lipid carriers (ARM-NLC) for enhanced intranasal delivery.
• To evaluate the safety and efficacy of ARM-NLC for nose-to-brain transport.
• To compare the brain targeting efficiency of ARM-NLC with conventional drug solutions.

Main Methods:

• Formulation of ARM-NLC using a microemulsion method and central composite design.
• Characterization of ARM-NLC particle size, zeta potential, and drug's physical state (DSC, XRD).
• In vitro cytotoxicity, in vitro release, ex vivo diffusion, pharmacokinetic, and brain uptake studies in animal models.

Main Results:

• Optimized ARM-NLC exhibited a particle size of 123.4 nm and zeta potential of -34.4 mV.
• Formulations were found to be non-toxic and safe for nasal administration.
• ARM-NLC demonstrated sustained release up to 96 hours and significantly higher brain drug concentrations compared to drug solutions.
• Brain-to-blood ratios indicated superior nose-to-brain transport for ARM-NLC, with high drug targeting efficiency (278.16%) and transport percentage (64.02%).

Conclusions:

• Optimized ARM-NLC are a safe and effective system for intranasal delivery of artemether.
• The nanostructured lipid carrier formulation significantly enhances direct nose-to-brain drug delivery.
• ARM-NLC presents a promising strategy for improving artemether's therapeutic efficacy via the intranasal route.