title: Intranasal H102 Peptide-Loaded Liposomes for Brain Delivery to Treat Alzheimer's Disease.
abstract: OBJECTIVE
  H102, a novel β-sheet breaker peptide, was encapsulated into liposomes to reduce its degradation and increase its brain penetration through intranasal administration for the treatment of Alzheimer's disease (AD).
  
  
  METHODS
  The H102 liposomes were prepared using a modified thin film hydration method, and their transport characteristics were tested on Calu-3 cell monolayers. The pharmacokinetics in rats' blood and brains were also investigated. Behavioral experiments were performed to evaluate the improvements on AD rats' spatial memory impairment. The neuroprotective effects were tested by detecting acetylcholinesterase (AchE), choline acetyltransferase (ChAT) and insulin degrading enzyme (IDE) activity and conducting histological assays. The safety was evaluated on rats' nasal mucosa and cilia.
  
  
  RESULTS
  The liposomes prepared could penetrate Calu-3 cell monolayers consistently. After intranasal administration, H102 could be effectively delivered to the brain, and the AUC of H102 liposomes in the hippocampus was 2.92-fold larger than that of solution group. H102 liposomes could excellently ameliorate spatial memory impairment of AD model rats, increase the activities of ChAT and IDE and inhibit plaque deposition, even in a lower dosage compared with H102 intranasal solution. H102 nasal formulations showed no toxicity on nasal mucosa.
  
  
  CONCLUSIONS
  The H102-loaded liposome prepared in this study for nasal administration is stable, effective and safe, which has great potential for AD treatment.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China.
authors.forename: Xiaoyao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China.
authors.forename: Xiayan
authors.initials: X
authors.lastname: Shao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Yuanzhen
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wan
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China. qzzhang@fudan.edu.cn.|Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Rd., Shanghai, 201203, People's Republic of China. qzzhang@fudan.edu.cn.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Shumei
authors.initials: S
authors.lastname: Xu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D008081:Liposomes; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D008081:Liposomes; D018696:Neuroprotective Agents; D010455:Peptides; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase
keywords: Alzheimer’s disease (AD); Brain delivery; H102 peptide; Intranasal administration; Liposome