Therapeutic effects of anti-amyloid β antibody after intravenous injection and efficient nose-to-brain delivery in Alzheimer's disease mouse model.
Administration route
Alzheimer’s disease
Amyloid β
Antibody drug
Nose-to-brain delivery
Journal
Drug delivery and translational research
ISSN: 2190-3948
Titre abrégé: Drug Deliv Transl Res
Pays: United States
ID NLM: 101540061
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
accepted:
04
01
2022
pubmed:
12
1
2022
medline:
28
9
2022
entrez:
11
1
2022
Statut:
ppublish
Résumé
Antibody drugs that target amyloid β (Aβ) are considered possible treatments for Alzheimer's disease; however, most have been dropped from clinical trials. We hypothesized that administration route for antiAβ antibody (AntiAβ) might affect its therapeutic potential and thus compared delivery of antibodies to the brain and their effect on cognitive dysfunction and amyloid disposition via intravenous (i.v.) and intranasal routes with and without the cell-penetrating peptide, L-penetratin. We demonstrated that intranasal administration with L-penetratin more efficiently delivered human immunoglobulin G (IgG), a model molecule for AntiAβ, to the brain compared with i.v. injection. We found that multiple intranasal treatments with Alexa 594-labeled AntiAβ (A594-AntiAβ) with L-penetratin significantly improved learning by mice with aged amyloid precursor protein (APP) knock-in (App KI mice). Further, intranasal administration of A594-AntiAβ increased the amount of soluble Aβ (1-42) in the brain, suggesting suppression of Aβ aggregation in insoluble form and involvement of activated microglia in Aβ clearance. Thus, administration route may be critical for efficient delivery of AntiAβ to the brain, and the nose-to-brain delivery with L-penetratin can maximize its therapeutic efficacy.
Identifiants
pubmed: 35015254
doi: 10.1007/s13346-022-01117-6
pii: 10.1007/s13346-022-01117-6
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Cell-Penetrating Peptides
0
Immunoglobulin G
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2667-2677Informations de copyright
© 2022. Controlled Release Society.
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