A novel multi-target strategy for Alzheimer's disease treatment via sublingual route: Donepezil/memantine/curcumin-loaded nanofibers

Topal, Fadime; Ertaş, Büşra; Güler, Ece; Gurbuz, Fatmanur; Özcan, Gül Sinemcan; Aydemir, Oğuzhan; Böcekçi, Veysel Gökhan; Duruksu, Gökhan; Cam, Cansun Sahin; Yazır, Yusufhan; Gündüz, Oğuzhan; Çam, Muhammet Emin

doi:10.1016/j.bioadv.2022.212870

Cited by 18 publications

(3 citation statements)

References 67 publications

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“…According to the SEM results, it was proven that the nanoparticles were produced using PLGA and PEG polymers with the double emulsion solvent evaporation technique. Furthermore, an increase obtained after encapsulating CUR in the particle size were found compatible with the literature [29]. In addition, these nanoparticle sizes were determined as enough small for making them to cross from the blood-brain barrier [30].…”

Section: Discussionsupporting

confidence: 84%

The production of curcumin-loaded PLGA/PEG nanoparticle for the treatment of Alzheimer’s disease

GULER,

CAM

2023

jrp

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Alzheimer's disease (AD) is the most common type of dementia in the world. This neurodegenerative disease affects 6.5 million people's lives by leading to functional impairments such as memory loss and cognitive regression. In the treatment of AD, there is no drug for radical treatment in the worldwide. Current treatment strategies provide relief to the symptoms. Therefore, curcumin (CUR) was preferred as a promising alternative therapeutic approach in this study. By using the double emulsion solvent evaporation technique, PLGA/PEG nanoparticles were produced and CUR was loaded to these nanoparticles (CNP). After that, the chemical structures and morphologies of CNP and PNP were analyzed by using FTIR and SEM. As a result, it was proven that these nanoparticles were produced by using PLGA and PEG polymers and CUR was loaded to these nanoparticles successfully.

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Section: Discussionsupporting

confidence: 84%

The production of curcumin-loaded PLGA/PEG nanoparticle for the treatment of Alzheimer’s disease

GULER,

CAM

2023

jrp

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“…The transnasal [10], transdermal [11],inner ear [12],sublingual [13],and buccal mucosa [14] routes can provide faster and better e cacy across BBB to treat central nervous system disorders than the traditional oral route. Xu [15] designed and developed an icariin nanogel loaded self-assembled thermosensitive hydrogel system (icariin-NGSTH) for the treatment of depression through the nasal route; the icariin-NGSTH signal was detected in the brain at 5 min, reached its strongest at 30 min, and the signal lasted up to 60 h, as seen on in-vivo uorescence imaging.…”

Section: Introductionmentioning

confidence: 99%

Factors affecting the penetration in microneedles and PLGA nanoparticle-assisted drug delivery: Importance of preparation and formulation

Deng

et al. 2023

Preprint

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Purpose Oral administration of the first-line antidepressant paroxetine (PAX) has certain limitations, including difficulty in reaching the brain due to oral absorption. Although there are many invasive and non-invasive strategies available to cross the blood–brain barrier (BBB), they run counter to long-term administration and convenience for patients. Methods We herein designed a simple PAX-loaded nanoparticle-integrated dissolving microneedles system (PAX-NP-DMNs), aiming to improve the bioavailability of PAX through the synergistic permeation-enhancing effect of microneedles (MNs) and nanoparticles (NPs). Results We assessed the NPs characteristics before and after MNs preparation and confirmed the successful construction of PAX-NP-DMNs based on differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. In the mechanical strength test, the addition of NPs increased the mechanical strength of dissolving MNs by 0.43 times and prolonged the release of PAX from 1 h to 48 h; PAX-NP-DMNs has over 40 times than PAX solution in the isolated skin penetration in permeability experiments. Moreover, PAX-NP-DMNs has good biocompatibility and does not cause adverse reactions. Conclusion Loading PAX into polylactic glycolic copolymer NPs and adding them into MNs can effectively improve the bioavailability of PAX and the mechanical strength problem of dissolving MNs. PAX-NP-DMNs can easily penetrate the skin to provide rapid and painless delivery without causing adverse effects, thus offering a more convenient and effective method for the treatment of central nervous diseases.

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“…The hallmarks of AD pathology include progressive memory loss and neuropathology, which is mainly caused by extracellular amyloid-beta (Aβ) plaques, neurofibrillary tangles, neuronal loss, and neuroinflammatory responses ( Guo et al, 2020 ). Despite decades of research, the molecular mechanism of AD pathogenesis is unclear, therefore, no effective treatments, especially drugs, have been shown to slow the progression of AD ( Mangialasche et al, 2010 ; Briggs et al, 2016 ; Haass and Selkoe, 2022 ; Panza and Lozupone, 2022 ; Slomski, 2022 ; Topal et al, 2022 ; Vandendriessche et al, 2022 ). Therefore, it is urgent to explore alternative targets to uncover the pathogenesis as well as for AD diagnosis and treatment.…”

Section: Introductionmentioning

confidence: 99%

Nucleosome assembly protein 1-like 5 alleviates Alzheimer’s disease-like pathological characteristics in a cell model

Wang

Liu

Sun

2022

Front. Mol. Neurosci.

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Alzheimer’s disease (AD) remains one of the most common dementias of neurodegenerative disease-related diseases. Nucleosome assembly protein 1-like 5 (NAP1L5) belongs to the NAP1L protein family, which acts as a histone chaperone. However, the function and mechanism of NAP1L5 in AD are still unclear. Bioinformatics analysis, RT-qPCR, and Western blotting results showed that NAP1L5 was downregulated in the brain tissues of AD patients and a mouse cell model of AD. NAP1L5 overexpression alleviated (Amyloid-β precursor protein) APP metabolism and Tau phosphorylation. We further demonstrated that NAP1L5 regulated the AD-like pathological characteristics through the GSK3B/Wnt/β-Catenin signaling pathway. Moreover, we showed that the Wnt/β-Catenin signaling pathway, regulated by NAP1L5, was mediated by AQP1-mediated mechanism in N2a-APP695sw cell. In sum, these results suggested that NAP1L5 overexpression has neuroprotective effects and might act as potential biomarker and target for the diagnosis and treatment of AD.

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A novel multi-target strategy for Alzheimer's disease treatment via sublingual route: Donepezil/memantine/curcumin-loaded nanofibers

Cited by 18 publications

References 67 publications

The production of curcumin-loaded PLGA/PEG nanoparticle for the treatment of Alzheimer’s disease

The production of curcumin-loaded PLGA/PEG nanoparticle for the treatment of Alzheimer’s disease

Factors affecting the penetration in microneedles and PLGA nanoparticle-assisted drug delivery: Importance of preparation and formulation

Nucleosome assembly protein 1-like 5 alleviates Alzheimer’s disease-like pathological characteristics in a cell model

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