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Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients

Background: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer’s Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn). Methods: We...

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Detalles Bibliográficos
Autores principales: Gagliardi, Stella, Truffi, Marta, Tinelli, Veronica, Garofalo, Maria, Pandini, Cecilia, Cotta Ramusino, Matteo, Perini, Giulia, Costa, Alfredo, Negri, Sara, Mazzucchelli, Serena, Bonizzi, Arianna, Sitia, Leopoldo, Busacca, Maria, Sevieri, Marta, Mocchi, Michela, Ricciardi, Alessandra, Prosperi, Davide, Corsi, Fabio, Cereda, Cristina, Morasso, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409287/
https://www.ncbi.nlm.nih.gov/pubmed/36012501
http://dx.doi.org/10.3390/ijms23169237
Descripción
Sumario:Background: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer’s Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn). Methods: We tested the BDC-HFn solubility, stability, and ability to cross a blood–brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq. Results: We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model. Conclusions: Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.