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
Fahimeh Nojoki, Bahman Ebrahimi-Hosseinzadeh, Ashrafalsadat Hatamian-Zarmi, Fariba Khodagholi, Khadijeh Khezri
Abstract
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).