Cellular transport study of RVG-9R-BACE1 siRNA complex included into uncoated (NR) and chitosan coated (C) solid lipid nanoparticles (SLN) using Caco-2 as a model of epithelial-like phenotypes. Display omitted •SLNs were proposed for an efficient and optimal nose-to-brain transport of BACE1 siRNA.•Coated and un-coated SLNs as nasal delivery system of BACE1 siRNA were designed.•RVG-9R/BACE1 siRNA complex was chosen for increasing transcellular nerve pathway.•Total encapsulation of RVG-9R/BACE1 siRNA was obtained with chitosan coating.•Chitosan coated and uncoated SLNs increase siRNA permeation through epithelial cells. 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.