Intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions improves cognitive impairments in a mouse model of Alzheimer's disease.

Autor: Zuglianello C; Laboratório de Farmacotécnica, Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis 88040-370, Santa Catarina, Brazil., França AP; Laboratório Experimental de Doenças Neurodegenerativas, Centro de Ciências Biológicas, Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Santa Catarina, Brazil., de Souza BS; Laboratório Experimental de Doenças Neurodegenerativas, Centro de Ciências Biológicas, Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Santa Catarina, Brazil., Agnes JP; Laboratório de Farmacologia e Bioquímica do Câncer, Centro de Ciências Biológicas, Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil., Prediger RD; Laboratório Experimental de Doenças Neurodegenerativas, Centro de Ciências Biológicas, Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Santa Catarina, Brazil., Lemos-Senna E; Laboratório de Farmacotécnica, Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis 88040-370, Santa Catarina, Brazil. Electronic address: lemos.senna@ufsc.br.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Nov; Vol. 281 (Pt 1), pp. 136158. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1016/j.ijbiomac.2024.136158
Abstrakt: Nasal delivery has emerged as a non-invasive route to administer drugs for brain delivery. In particular, polyelectrolyte complexes-based nanocarriers have been demonstrated to be advantageous for nasal delivery of peptide drugs and vaccines. Pramlintide (Pram) is a peptide that emerges as a novel neuroprotective strategy to modify the pathogenesis of Alzheimer's disease (AD). In this study, we examined the effects of the intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions (PEC-NE DexS/Pram ) in an experimental model of AD induced by intracerebroventricular (i.c.v.) infusion of amyloid-beta (Aβ 1 - 42 ) peptide in mice. PEC-NE DexS/Pram displayed droplet size lower than 200 nm and a negatively charged surface. The locomotor activity of the animals was not affected by the i.c.v. Aβ 1 - 42 injection or Pram treatment. On the other hand, the intranasal administration of PEC-NE DexS/Pram at a dose of 100 μg/day for 14 consecutive days restored the impairment induced by Aβ 1 - 42 injection in the discriminative learning and the short-term spatial reference memory of mice. However, Pram treatment did not alter the Aβ 1 - 42 -induced anhedonic behavior, oxidative stress parameters, or the pre-synaptic SNAP-25 and post-synaptic PSD-95 levels in the hippocampus and prefrontal cortex. These findings indicate cognitive-enhancing properties of intranasal Pram administration in an animal model of AD.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elenara Lemos-Senna reports a relationship with National Council for Scientific and Technological Development that includes:. Carine Zuglianello reports a relationship with Coordination of Higher Education Personnel Improvement that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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