Chitosan nanoparticles to enhance nasal absorption and brain targeting of sitagliptin to treat Alzheimer's disease

Alzheimer's disease (AD), a highly complex, irreversible, progressive, challenging as well as fatal neurodegenerative disease of the brain, affects 35 million people around the world. It is estimated that 100 million people are expected to suffer from the disorder by 2050. It was found that sitagliptin (SIT), a dipeptidyl peptidase-4 (DPP-4) inhibitor, produced symptomatic relief of AD. Sitagliptin loaded chitosan nanoparticles (SIT-CS-NPs) were prepared and evaluated for their potential to target sitagliptin into the brain following intranasal (IN) administration. The SIT-CS-NPs were formulated by ionic gelation method. The mean size and zeta potential was 188.4 ± 48.1 nm and 20.8 mV respectively. In vitro SIT release in pH 6.4 phosphate buffer ranged between 49.55 ± 2.62 %w/w and 73.77 ± 2.12 %w/w for 24 h. Animal studies revealed that SIT-CS-NPs increased SIT levels in the brain by 5.07 fold in comparison with free SIT after IN administration.