Treating Alzheimer’s Disease via Donepezil Hydrochloride Loaded Nanoparticles: A Novel Approach for Brain Drug Delivery

Abstract Background Many neuroprotective agents (like donepezil hydrochloride) have poor permeation to brain through blood brain barrier. Thus, there is a need to develop a new drug delivery system that can improvise the release of neuroprotective agents/drugs directly into brain avoiding blood brain barrier. Method Donepezil hydrochloride loaded chitosan nanoparticles were developed by ionic gelation method and optimized using Design of Experiment (DoE) approach. Result The optimized formulation had shown mean particle size (177.8 nm), zeta potential (+ 16.6 mV), drug payload (22.2 mg/100 mg of chitosan), process yield (91.96%) and mucoadhesive strength (9.26 g). In‐vitro release and ex‐vivo diffusion of drug from nanoparticles were found be > 90% and >70% in 24 hours, respectively. The delivery of drug to rat brain was found to be three times higher with nanoparticles vis‐à‐vis its solution. Further, confocal laser scanning microscopy confirmed the grater extent of localization by nanoparticles in the brain after nasal administration. Conclusion From the above results, it was concluded that the nose to brain delivery of donepezil hydrochloride using mucoadhesive nanoparticles has better potential as compared to conventional formulation approach for brain drug delivery.