Antioxidative NAC-Loaded Silk Nanoparticles with Opening Mucosal Tight Junctions for Nasal Drug Delivery: An In Vitro and In Vivo Study

Abstract

Using nasal routes to deliver drugs to the brain using multifunctional nanoparticles (NPs) to bypass the blood–brain barrier (BBB) might enhance the delivery efficacy. Anti-oxidative N-Acetyl-L-cysteine (NAC)-loaded silk fibroin (SF/NAC) NPs are produced, characterized and studied as a potential delivery vehicle for NAC delivered to the brain via nasal for both in vitro and in vivo studies. The NPs are not cytotoxic to RPMI 2650 cells, mucosal model cells, at a concentration of 6000 μg/mL. The anti-oxidative activities of SF/NAC NPs are demonstrated by high H2O2 scavenge capacities of the NPs and shown by mitochondrial superoxide (MitoSOX) immunostaining of human mesenchymal stem cells. Tight junctions in RPMI 2650 cells are opened after 30 min of incubation with SF/NAC NPs, which are demonstrated by measuring the decrease in trans-epithelial electrical resistance (TEER) values and discreteness in ZO-1 stains. The cellular uptake of SF/NAC NPs by RPMI 2650 cells is significantly greater than that for SF NPs and increased with increasing incubation time. In an in vivo imaging study (IVIS) using rats shows that the amount of NAC that is delivered to the brain by SF/NAC NPs increased by 1.40–2.60 times and NAC is retained longer in the nasal cavity than NAC solutions in a 2-h study.

Progress in silk and silk fiber-inspired polymeric nanomaterials for drug delivery

“…Frontiers in Chemical Engineering frontiersin.org organic solvent desolvation (Hasanzadeh et al, 2020;Rezaei et al, 2020;Zahedi et al, 2021), salting out (Song et al, 2019), and microfluidic devices (Shimanovich et al, 2017;Matthew et al, 2020;Vargas Montoya et al, 2020;Matthew et al, 2022;Tomeh et al, 2022) (Table 1). Control of particle size and material properties to enhance cell material interaction (Xiao et al, 2022) and to optimize non-systemic delivery routes has been established (Takeuchi et al, 2019;Yang et al, 2019;Chung et al, 2022;Mitra et al, 2022).…”

Ag- but Not ZnO-Nanoparticles Disturb the Airway Epithelial Barrier at Subtoxic Concentrations

“…This mechanism of so-called nose-to-brain delivery is used for intranasal drug administration. It allows bypassing the blood-brain barrier, which, in the case of medical treatment, leads to a desired potent and targeted accumulation of the drug in the nervous system [22]. For inhaled NP, the same fate would likely be problematic.…”