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.

Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer's therapy / Rassu, Giovanna; Soddu, Elena; Posadino, Anna Maria; Pintus, Gianfranco; Sarmento, Bruno; Giunchedi, Paolo; Gavini, Elisabetta. - In: COLLOIDS AND SURFACES. B, BIOINTERFACES. - ISSN 0927-7765. - 152:(2017), pp. 296-301. [10.1016/j.colsurfb.2017.01.031]

Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer's therapy

RASSU, Giovanna;SODDU, Elena;POSADINO, Anna Maria;PINTUS, Gianfranco;GIUNCHEDI, Paolo;GAVINI, Elisabetta
2017-01-01

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.
2017
Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer's therapy / Rassu, Giovanna; Soddu, Elena; Posadino, Anna Maria; Pintus, Gianfranco; Sarmento, Bruno; Giunchedi, Paolo; Gavini, Elisabetta. - In: COLLOIDS AND SURFACES. B, BIOINTERFACES. - ISSN 0927-7765. - 152:(2017), pp. 296-301. [10.1016/j.colsurfb.2017.01.031]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/173725
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 182
  • ???jsp.display-item.citation.isi??? 158
social impact