Alzheimer's disease (AD) is the most common cause of dementia worldwide, 50 million people today are affected by this disease globally. Alzheimer's disease has had a tremendous impact on the affected individual, caregiver, and society, in both developed and developing nations. There are many causes of Alzheimer's disease, but the main hypotheses are cholinergic and amyloid hypotheses. In addition, several factors such as head injury, infection, increased age, vascular disease, and genetic factors play a vital role in the disease incident. Donepezil is a reversible choline esterase inhibitor, approved by the FDA in 1996 to relieve disease symptoms, but not for a cure and prevent disease. This drug's main problem and difficulty is a high protein bind, and only 15.7% of the drug can cross the blood-brain barrier (BBB), which is very low. So here, in this study, the donepezil hydrochloride drug tried to bind with gold nanocomposite to enhance the penetration of the drug into the brain and increase its efficiency. So, firstly the gold nanoparticle drug delivery system of donepezil hydrochloride was prepared by using chitosan as a stabilizing agent. Donepezil-gold nanocomposite was prepared by co-precipitation technique and characterized for particle size, loading efficiency, and zeta potential by using Minitab- placket -Burmars design. The results were obtained by using different levels of chitosan and gold NPs, and the drug's higher-level loading efficiency is about 69.2, and a lower level is about 10.5, while the concentration of gold is the same in both experiments, but the concentration of the drug differs. This confirms that the drug has a significant effect on loading efficiency. The smallest particle size obtained by trials is about 48 nm. And for the zeta potential, it ranges between (18.5 and 30.4) mV. The FTIR analysis were conducted to ensure that the drug has been intercalated on gold nanoparticles or not, the result revealed that shifted into two peaks of donepezil hydrochloride drug when bind in gold nanoparticles. The XRD pattern of Done-gold nanocomposites shown the existence of chitosan peak at 2? = 19.4° as well as those of gold nanoparticles at 2?= 38.2°, 43.8° and 64.5° that can be due to the 111, 200 and 220 planes, respectively. These three peaks confirmed that the Au nanoparticles exist in the sample. The release of the drug from nanocomposites were performed as PH=7.4 and 40% of the drug was released after 50 minutes and the maximum release of 75% reached after 1440 minutes. Using UV-Vis spectroscopy, gold nanoparticle produces a high absorbance band in the visible region (517 nm). Finally, the optimum formula with the highest loading efficiency, smallest particle size, and optimum zeta potential, the following are needed, (1.5) g of chitosan, (39.1975) mg of the drug, and finally, (24.6) mg of gold. to produce a formula with (42.7183%) loading efficiency, (102.4918) mg of particle size, and (26.3060) nm of zeta potential.

Gold Nanoparticles Loaded with Chitosan Encapsulate Donepezil as a Novel Nanocomposite for Alzheimer’s Disease Therapy