Nose to brain delivery of insulin loaded in PLGA and chitosan-coated PLGA nanoparticles: A promising approach for Alzheimer's disease therapy

Abstract

Alzheimer's disease is considered one of the most common leading causes of death worldwide. Recent evidence shows that intranasal delivery of insulin can serve as a significant pharmacological therapy for Alzheimer's disease due to a direct nose-to-brain connection. To tackle the challenges of nose-to-brain drug delivery, the current study investigated the use of PLGA nanoparticles (NPs) and mucoadhesive chitosan-coated PLGA NPs (PLGA/chit). The effect of NPs on insulin permeability on sheep nasal mucosa showed that PLGA and PLGA/chit NPs led to a 4-fold and 16-fold increase in comparison to insulin solution, respectively. Moreover, the findings showed that the formulation of NPs enhanced the area under the curve (AUC) of insulin in the brain compared to the insulin solution. The results demonstrate that the presence of a chitosan coating on the NPs resulted in a notable increase in brain concentration compared to NPs without the coating (p < 0.01). The sustained release of insulin from the NPs, particularly those coated with chitosan, led to a reduction in plasma concentration and mitigated the systemic adverse effects of insulin.

In summary, the results suggest that intranasal administration of NPs, particularly mucoadhesive NPs, has the potential to enhance the delivery of insulin to the brain.