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Pharmaceutical Research

, Volume 32, Issue 12, pp 3837–3849 | Cite as

Intranasal H102 Peptide-Loaded Liposomes for Brain Delivery to Treat Alzheimer’s Disease

  • Xiaoyao Zheng
  • Xiayan Shao
  • Chi Zhang
  • Yuanzhen Tan
  • Qingfeng Liu
  • Xu Wan
  • Qizhi ZhangEmail author
  • Shumei Xu
  • Xinguo Jiang
Research Paper

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.

KEY WORDS

H102 peptide Liposome Intranasal administration Brain delivery Alzheimer’s disease (AD) 

ABBREVIATIONS

AChE

Acetylcholinesterase

AD

Alzheimer’s disease

β-amyloid protein

BBB

Blood–brain barrier

CD

Circular dichroism

ChAT

Choline acetyltransferase

CNS

Central nervous system

CL

Cerebellum

CR

Cerebrum

EPC

Egg phosphatidylcholine

HI

Hippocampus

IDE

Insulin degrading enzyme

OB

Olfactory bulb

PEG

Poly ethylene glycol

TEER

Transendothelial electrical resistance

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by grants from the National Science and Technology Major Project 2009ZX09103-029 and The Open Project Program of Key Lab of Smart Drug Delivery (Fudan University), Ministry of Education, China.

Supplementary material

11095_2015_1744_MOESM1_ESM.docx (14 kb)
Table S1 (DOCX 13 kb)
11095_2015_1744_MOESM2_ESM.docx (15 kb)
Table S2 (DOCX 15 kb)
11095_2015_1744_MOESM3_ESM.docx (15 kb)
Table S3 (DOCX 14 kb)
11095_2015_1744_MOESM4_ESM.docx (102 kb)
Fig. S1 (DOCX 101 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Xiaoyao Zheng
    • 1
  • Xiayan Shao
    • 1
  • Chi Zhang
    • 1
  • Yuanzhen Tan
    • 2
  • Qingfeng Liu
    • 1
  • Xu Wan
    • 1
  • Qizhi Zhang
    • 1
    • 3
    Email author
  • Shumei Xu
    • 2
  • Xinguo Jiang
    • 1
  1. 1.Key Laboratory of Smart Drug DeliveryMinistry of Education (Fudan University)ShanghaiPeople’s Republic of China
  2. 2.Department of PhysiologyTianjin Medical UniversityTianjinPeople’s Republic of China
  3. 3.Department of Pharmaceutics, School of PharmacyFudan UniversityShanghaiPeople’s Republic of China

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