Nanostructured Lipid Carriers Loaded with Donepezil for Nose-to-Brain Targeting.

Area of Science:

• Nanotechnology
• Pharmaceutical Sciences
• Neuroscience

Background:

• Oral donepezil administration causes systemic side effects due to fluctuating concentrations.
• Developing targeted drug delivery systems is crucial for improving therapeutic efficacy and reducing toxicity.

Purpose of the Study:

• To develop and characterize nanostructured lipid carriers loaded with donepezil (donepezil-NLC) for enhanced nose-to-brain delivery.
• To evaluate the pharmacokinetic profile and brain targeting efficiency of donepezil-NLC after intranasal administration.

Main Methods:

• Characterization of donepezil-NLC: particle size, polydispersity index, zeta potential, encapsulation efficiency, microscopy, thermal analysis, and spectroscopy.
• In vitro drug release studies.
• In vivo pharmacokinetic studies in Wistar rats following intranasal administration of donepezil-NLC and intravenous injection of donepezil.

Main Results:

• Donepezil-NLC exhibited nanometric size, high encapsulation efficiency, and an amorphous lipid matrix with molecularly dispersed donepezil.
• In vitro release studies showed a biphasic pattern (initial burst followed by sustained release), fitting the Korsmeyer-Peppas model.
• Intranasal administration of donepezil-NLC resulted in a 10.5-fold higher AUC0-∞ compared to intravenous donepezil, indicating significantly improved brain bioavailability and effective nose-to-brain targeting.

Conclusions:

• Donepezil-NLC is an effective drug delivery system for direct nose-to-brain transport.
• This system holds potential for reducing systemic toxicity and adverse effects in Alzheimer's disease treatment.
• Utilizing donepezil-NLC may allow for lower therapeutic doses and improved patient outcomes.