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AuthorRassu, Giovanna
AuthorSoddu, Elena
AuthorPosadino, Anna Maria
AuthorPintus, Gianfranco
AuthorSarmento, Bruno
AuthorGiunchedi, Paolo
AuthorGavini, Elisabetta
Available date2017-03-14T08:10:55Z
Publication Date2017-04-01
Publication NameColloids and Surfaces B: Biointerfacesen_US
CitationRassu, Giovanna. Soddu, Elena. Posadino, Anna Maria. Pintus, Gianfranco. Sarmento, Bruno. Giunchedi, Paolo. Gavini, Elisabetta. "Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer’s therapy", 2017, Vol. 152, p.p. 296-301
AbstractAbstract We designed a delivery system to obtain an efficient and optimal nose-to-brain transport of BACE1 siRNA, potentially useful in the treatment of Alzheimer's disease. We selected a cell-penetrating peptide, the short peptide derived from rabies virus glycoprotein known as RVG-9R, to increase the transcellular pathway in neuronal cells. The optimal molar ratio between RVG-9R and BACE1 siRNA was elucidated. The complex between the two was then encapsulated. We propose chitosan-coated and uncoated solid lipid nanoparticles (SLNs) as a nasal delivery system capable of exploiting both olfactory and trigeminal nerve pathways. The coating process had an effect on the zeta potential, obtaining positively-charged nanoparticles, and on siRNA protection. The positive charge of the coating formulation ensured mucoadhesiveness to the particles and also prolonged residence time in the nasal cavity. We studied the cellular transport of siRNA released from the SLNs using Caco-2 as a model of epithelial-like phenotypes. We found that siRNA permeates the monolayer to a greater extent when released from any of the studied formulations than from bare siRNA, and primarily from chitosan-coated SLNs.
SubjectRVG-9R cell-penetrating peptide
SubjectNose-to-brain transport
SubjectSolid lipid nanoparticle
TitleNose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer’s therapy
Volume Number152

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