Journal
PHARMACEUTICS
Volume 14, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics14091976
Keywords
brain disorders; curcuminoids; drug delivery systems; mesoporous silica nanoparticles; neurodegenerative disorder
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Funding
- Sao Paulo Research Foundation (FAPESP, Brazil) [2014/50928-2, 2019/19228-8, 2018/25377-3]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) [001]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil) [465687/2014-8]
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This study investigated the use of curcumin-loaded mesoporous silica nanoparticles (MSN-CCM) and a thermo-responsive hydrogel for the treatment of Alzheimer's disease (AD). The results showed that the MSN-CCM and hydrogel had excellent properties and high permeation values. In vivo studies confirmed the potential of the hydrogel-MSN-CCM formulation in reverting cognitive deficits in an AD model.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment. Curcumin-loaded mesoporous silica nanoparticles (MSN-CCM) can overcome the drawbacks related to the free curcumin (CCM) clinical application, such as water insolubility and low bioavailability, besides acting over the main causes associated to AD. A thermo-responsive hydrogel is an interesting approach for facilitating the administration of the nanosystem via a nasal route, as well as for overcoming mucociliary clearance mechanisms. In light of this, MSN-CCM were dispersed in the hydrogel and evaluated through in vitro and in vivo assays. The MSNs and MSN-CCM were successfully characterized by physicochemical analysis and a high value of the CCM encapsulation efficiency (EE%, 87.70 +/- 0.05) was achieved. The designed thermo-responsive hydrogel (HG) was characterized by rheology, texture profile analysis, and ex vivo mucoadhesion, showing excellent mechanical and mucoadhesive properties. Ex vivo permeation studies of MSN-CCM and HG@MSN-CCM showed high permeation values (12.46 +/- 1.08 and 28.40 +/- 1.88 mu g cm(-2) of CCM, respectively) in porcine nasal mucosa. In vivo studies performed in a streptozotocin-induced AD model confirmed that HG@MSN-CCM reverted the cognitive deficit in mice, acting as a potential formulation in the treatment of AD.
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