Pharmacokinetic behavior and efficiency of acetylcholinesterase inhibition in rat brain after intranasal administration of galanthamine hydrobromide loaded flexible liposomes

Galanthamine hydrobromide (GH) has been approved for symptomatic treatment of Alzheimer's disease (AD) and vascular dementia. Hence, the effects of intranasal administration of GH loaded flexible liposomes have been investigated for the first time on the efficiency of acetylcholinesterase inhibition, as well as the pharmacokinetic behavior of GH in rat brain. The GH loaded flexible liposomes were characterized for shape, entrapment capacity, size distribution and zeta potential by transmission electron microscopy (TEM), ultracentrifugation and dynamic light scattering (DLS), respectively. The inhibition of acetylcholinesterase was investigated using rat brain homogenates as an enzyme resource and microdialysis was used to determine the pharmacokinetic behavior of GH in rats brain. The rat pheochromocytoma PC-12 cell line was used to evaluate the cytotoxicity of GH loaded flexible liposomes. The results revealed that: (i) the efficiency of acetylcholinesterase inhibition of GH was greatly enhanced by intranasal administration compared with oral administration, especially GH loaded in flexible liposomes; (ii) the Cmax and AUC0→10 for intranasal administration of GH loaded flexible liposomes were 3.52 and 3.36 times higher than those of orally administered GH, moreover, the Tmax was greatly shortened from 1.5 h for oral administration to 0.75 h for intranasal administration of GH loaded flexible liposomes; and (iii) PC-12 cells viability tests showed that the flexible liposome carrier is not toxic to the cultured cells and the cytotoxicity of GH to cells was clearly decreased by loading in flexible liposomes. These results indicate that intranasal administration of GH loaded flexible liposomes could readily transport GH into brain tissues, suggesting some promise for this approach in successful brain–drug targeting in AD treatment.

► Effect of galanthamine hydrobromide was enhanced by intranasal administration, especially loaded in flexible liposomes.
► Intranasal administration of galanthamine hydrobromide could readily transport it through the blood–brain barriers.
► Intranasal administration is may be a promising technology for AD treatment.