title: Pharmacokinetic behavior and efficiency of acetylcholinesterase inhibition in rat brain after intranasal administration of galanthamine hydrobromide loaded flexible liposomes.
abstract: 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 C(max) and AUC(0→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 T(max) was greatly shortened from 1.5h for oral administration to 0.75h 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.
authors.affiliation: College of Pharmacy, Xi'an Medical University, Xi'an 710021, PR China; Institute of Drug Research and Development, Fengyuan Pharmaceutical Limited Company, Ruicheng 044600, PR China.
authors.forename: Weize
authors.initials: W
authors.lastname: Li
authors.affiliation: Center of Nanjing Hailing R&D for Chinese Traditional Medicine Pharmaceutical Technology, Nanjing 210049, PR China. Electronic address: zhouyongqiangs1@163.com.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: College of Pharmacy, Xi'an Medical University, Xi'an 710021, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.affiliation: School of Science and Life, Northwest University, Xi'an 710069, PR China.
authors.forename: Baohua
authors.initials: B
authors.lastname: Hao
authors.affiliation: College of Pharmacy, Xi'an Medical University, Xi'an 710021, PR China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Drug Research and Development, Fengyuan Pharmaceutical Limited Company, Ruicheng 044600, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Kong
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005702:Galantamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes; D008297:Male; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002800:Cholinesterase Inhibitors; D008081:Liposomes; D005702:Galantamine; D000110:Acetylcholinesterase