Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core-Shell Silica Nanoparticles.

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C' dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C' dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C' dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.

Non-Equilibrium Block Copolymer Self-Assembly Based Porous Membrane Formation Processes Employing Multicomponent Systems.

Porous polymer-derived membranes are useful for applications ranging from filtration and separation technologies to energy storage and conversion. Combining block copolymer (BCP) self-assembly with the industrially scalable, non-equilibrium phase inversion technique (SNIPS) yields membranes comprising periodically ordered top surface structures supported by asymmetric, hierarchical substructures that together overcome performance tradeoffs typically faced by materials derived from equilibrium approaches. This review first reports on recent advances in understanding the top surface structural evolution of a model SNIPS-derived system during standard membrane formation. Subsequently, the application of SNIPS to multicomponent systems is described, enabling pore size modulation, chemical modification, and transformation to non-polymeric materials classes without compromising the structural features that define SNIPS membranes. Perspectives on future directions of both single-component and multicomponent membrane materials are provided. This points to a rich and fertile ground for the study of fundamental as well as applied problems using non-equilibrium-derived asymmetric porous materials with tunable chemistry, composition, and structure.