Permeability of Novel Chitosan-g-Poly(Methyl Methacrylate) Amphiphilic Nanoparticles in a Model of Small Intestine In Vitro.

Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropically crosslinked with sodium tripolyphosphate. In this work, we synthesized, for the first time, chitosan-g-poly(methyl methacrylate) nanoparticles thiolated by the conjugation of N-acetyl cysteine. First, we confirmed that both non-crosslinked and crosslinked nanoparticles in the 0.05⁻0.1% w/v concentration range display very good cell compatibility in two cell lines that are relevant to oral delivery, Caco-2 cells that mimic the intestinal epithelium and HT29-MTX cells that are a model of mucin-producing goblet cells. Then, we evaluated the effect of crosslinking, nanoparticle concentration, and thiolation on the permeability in vitro utilizing monolayers of (i) Caco-2 and (ii) Caco-2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco-2 monolayer was affected by the crosslinking. In addition, thiolated nanoparticles interact more strongly with mucin, resulting in a decrease of the apparent permeability coefficient (Papp) compared to the pristine nanoparticles. Moreover, for all the nanoparticles, higher concentration resulted in lower Papp, suggesting that the transport pathways can undergo saturation.

Pore and ligament size control, thermal stability and mechanical properties of nanoporous single crystals of gold.

Nanoporous gold is widely used in research and nanotechnology because of its diverse properties, including high surface area and catalytic activity. The ligament size is usually considered as one of the main parameters controlling thermal stability and mechanical properties of nanoporous gold. Recently we developed a method for creating nanoporous single crystal gold particles using eutectic decomposition of Au-Ge, followed by selective etching of Ge. Here, we used this novel method to create nanoporous gold particles with controlled ligament sizes by changing the initial sample's relative concentrations of gold and germanium. When investigated over 1-4 h at 250-400 °C the material was thermally stable up to 350 °C, which is higher than the thermal stability of "classical" nanoporous gold prepared by dealloying. Mechanical properties were examined utilizing nanoindentation of nanoporous gold before and after annealing. For smaller ligament sizes, hardness increased with annealing temperature up to 300 °C and then strongly decreased. For larger ligament sizes, hardness decreased with increasing annealing temperature. Young's modulus was unchanged up to 300 °C.