title: Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer's therapy.
abstract: 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.
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Muroni 23a, 07100, Sassari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rassu
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Muroni 23a, 07100, Sassari, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Soddu
authors.affiliation: Department of Biomedical Sciences, University of Sassari, viale San Pietro 43b, 07100, Sassari, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Posadino
authors.affiliation: Department of Biomedical Sciences, College of Health Science, Qatar University, P.O. Box 2713, Doha, Qatar.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pintus
authors.affiliation: CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116, Gandra-PRD, Portugal; INEB, Instituto de Engenharia Biomédica, Rua do Campo Alegre, 823, 4150-180, Porto, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Muroni 23a, 07100, Sassari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Muroni 23a, 07100, Sassari, Italy. Electronic address: eligav@uniss.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D018938:Caco-2 Cells; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009297:Nasal Mucosa / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D034741:RNA, Small Interfering; D048271:Chitosan; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Chitosan; Nose-to-brain transport; RVG-9R cell-penetrating peptide; Solid lipid nanoparticle; siRNA