Design and development of chitosan-insulin-transfersomes (Transfersulin) as effective intranasal nanovesicles for the treatment of Alzheimer’s disease: In vitro, in vivo, and ex vivo evaluations

This study aimed to prepare and characterize chitosan-Transfersulin (CTI) as an effective intranasal drug delivery
system (IDDS) for the treatment of memory disorders by mediating insulin (INS) transport into the brain. Tween
80 was used as an edge activator and chitosan (CS) to increase the elasticity of CTI. CTI nanovesicles were
prepared by the film hydration method and characterized after optimization. Optimal values of particle size,
polydispersity index, zeta potential, encapsulation efficiency, and drug loading were found to be 137.9 ± 28.2
nm, 0.20, + 23.4 mV, 65.1 ± 0.9 %, and 9.1 ± 0.4 %, respectively. The TEM image supported these findings.
FTIR and TGA also demonstrated suitable entrapment of INS in CTI without any chemical interaction. The circular
dichroism and fluorescence spectroscopy results confirmed INS’s stability and structural integrity released
from the CTI. The nasal uptake of INS loaded into CTI was confirmed by optical fluorescence imaging. Histological
inspections of the hippocampus also confirmed the results of the behavioral tests. In conclusion, these
nanoformulations exhibited greater neuroprotective effects on rats via increased intracellular drug uptake and
sustained retention, and it appears to be a promising and effective IDDS for treating Alzheimer’s disease (AD).