PEGylated silicon nanowire coated silica microparticles for drug delivery across intestinal epithelium

Abstract

Composite particles made by growing nanoscopic silicon wires from the surface of monodispersed, microsized silica beads were tested in this study for their ability to affect the integrity and permeability of an epithelial cell layer. Polyethylene glycol (PEG) is known to sterically stabilize particles and prevent protein binding; as such, it is a routine way to impart in vivo longevity to drug carriers. The effect of the silica beads, both with and without silicon nanowires and PEG, on the disruption of the tight junctions in Caco-2 cells was evaluated by means of: (a) analysis of the localization of zonula occludens-1 (ZO-1), claudin-1 and f-actin; (b) measurements of trans-epithelial electrical resistance (TEER); (c) real-time quantitative RT-PCR analysis of the expression of PKC-α and PKC-z, which regulate the fluidity of cell membranes, and RhoA and Rac1, which are mainly involved in mechanotransduction processes; and (d) drug permeability experiments with fluorescein-sodium. The results have shown that Si-nanowire-coated silica microparticles added to Caco-2 cells in culture lead to alterations in tight junction permeability and the localization of ZO-1 and f-actin, as well as to decreased width of ZO-1 and claudin-1 at the tight junction and increased expression of PKC transcripts. Si-nanowire-coated silica microparticles increased the permeability of Caco-2 cell monolayers to fluorescein-sodium in proportion to their amount. Effects indicative of loosening the Caco-2 cell monolayers and increasing their permeability were less pronounced for PEGylated particles, owing to their greater supposed inertness in comparison with the non-functionalized beads and nanowires. The analyzed Si-nanowire-coated silica microparticles have thus been shown to affect membrane barrier integrity in vitro, suggesting the possibility of using nanostructured microparticles to enhance drug permeability through the intestinal epithelium in vivo.

Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse

“…For example, mucoadhesion of pharmaceutical devices to surfaces that experience constant physical stress and drug clearance on the order of seconds to minutes, such as the buccal or ocular surfaces, can markedly improve drug delivery [43]. Also, devices generally larger in size than the thickness of the mucus barrier, such as micropatches [44, 45] and large microspheres functionalized with silicon nanowires [46], may be able to interact directly with the underlying mucosa to increase residence time in the GI tract. The distinction between mucus adhesion and mucosa adhesion is very important, and size scale is one factor that determines the efficiency by which a system designed to stick to the mucosal epithelium may contact the epithelium, as opposed to becoming trapped in the mucus gel instead.…”

Multifunctional hydroxyapatite and poly(d,l-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

“…At the same time, 2 mg/cm 2 of HAp, HAp/D 3 and HAp/D 3 /PLGA were added to the cells, separately. The subsequent incubation lasted for 7 days, during which α-MEM supplemented with 50 μg/ml AA was replenished every 48 h. After the given period, one portion of cells was fixed for 15 min in 3.7 wt.% paraformaldehyde at room temperature and then stained for f-actin and nucleus using phalloidin-tetramethylrhodamine (AlexaFluor 555, Invitrogen) and 4′,6-diamidino-2-phenylindole dihydrochloride nuclear counterstain (DAPI, Invitrogen), following a previously described protocol [18]. …”

When 1 + 1 > 2: Nanostructured composites for hard tissue engineering applications

“…Bioactive glass with the SiO 2 :CaO molar ratio of 5 also slightly improved the compressive strength of PLGA scaffolds and the osteogenic response of MSCs seeded on them 121 . Compared to CAP nanoparticles typified by swift reorganization of the surface layers and the virtual impossibility of their chemical functionalization, silanol groups on the surface of silica nanoparticles offer a far greater stability and more facile functionalization with organic molecules 122 . Silicon is also present in the newly formed bone in the amount of 0.5 wt% 123 , and the biological response to implantation of Si-doped HAp was more positive than for pure HAp 124,125 .…”