Design, Development, Optimization and Characterization of Donepezil Loaded Chitosan Nanoparticles for Brain Targeting to Treat Alzheimer's Disease

作者：Bhavna; Md Shadab; Ali Mushir; Bhatnagar Aseem; Baboota Sanjula; Sahni Jasjeet Kaur; Ali Javed^*

来源：Science of Advanced Materials, 2014, 6(4): 720-735.

DOI：10.1166/sam.2014.1761

• Alzheimer Disease
• Biodistribution
• Brain Targeting
• Chitosan
• Donepezil
• Gamma Scintigraphy
• Intranasal
• Nanoparticles
• Response Surface Methodology
• Stability Study

The purpose of the present study was to investigate the possibility of targeting an anti-Alzheimer's drug donepezil in the brain using polymeric nanoparticles. The Donepezil loaded chitosan nanoparticles were prepared by ionic gelation method to improve the bioavailability and enhance the uptake of donepezil to the brain via intranasal delivery. The formulations were optimized on the basis of response surface methodology. Donepezil loaded chitosan nanoparticles were developed and characterized for particle size, size distribution, zeta potential, entrapment efficiency, drug loading, in vitro drug release and in vivo studies using gamma scintigraphy techniques. The TEM and SEM images of the formulation suggested that particle size was within 100-200 nm and particles were spherical in shape with smooth morphology. The biodistribution studies after intranasal administered in rats showed higher percentage of radioactivity per gram in the brain for the donepezil loaded chitosan nanoparticles formulation as compared to donepezil solution (p <0.05) which are indicative of direct nose to brain transport. The higher drug transport efficiency (191.398%) and direct transport percentage (1834.480%) were found with chitosan nanoparticles as compared to donepezil solution. These results suggest that intranasally administered chitosan nanoparticles have better brain targeting efficiency and are a promising approach for treatment of Alzheimer disease.

• 出版日期2014-4