Xiaoyao Zheng1, Xiayan Shao1, Chi Zhang1, Yuanzhen Tan2, Qingfeng Liu1, Xu Wan1, Qizhi Zhang3,4, Shumei Xu2, Xinguo Jiang1. 1. Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China. 2. Department of Physiology, Tianjin Medical University, Tianjin, 300070, People's Republic of China. 3. Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, People's Republic of China. qzzhang@fudan.edu.cn. 4. Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Rd., Shanghai, 201203, People's Republic of China. qzzhang@fudan.edu.cn.
Abstract
PURPOSE: 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.
PURPOSE: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 ADrats' 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: Jyrki Lötjönen; Robin Wolz; Juha Koikkalainen; Valtteri Julkunen; Lennart Thurfjell; Roger Lundqvist; Gunhild Waldemar; Hilkka Soininen; Daniel Rueckert Journal: Neuroimage Date: 2011-01-31 Impact factor: 6.556
Authors: Gisele C Vaz; Neeru M Sharma; Hong Zheng; Matthew C Zimmerman; Robson S Santos; Frederic Frezard; Marco A P Fontes; Kaushik P Patel Journal: J Neurosci Methods Date: 2016-08-11 Impact factor: 2.390