Nanoparticle-based therapeutic formulations are being increasingly explored for the treatment of various ailments. Despite numerous advances, the success of nanoparticle-based technologies in treating brain diseases has been limited. Translational hurdles of nanoparticle therapies are attributed primarily to their limited ability to cross the blood-brain barrier (BBB), which is one of the body's most exclusive barriers. Several efforts have been focused on developing affinity-based agents and using them to increase nanoparticle accumulation at the brain endothelium. Very little is known about the role of fundamental physical parameters of nanoparticles such as size, shape, and flexibility in determining their interactions with and penetration across the BBB. Using a three-dimensional human BBB microfluidic model (μHuB), we investigate the impact of these physical parameters on nanoparticle penetration across the BBB. To gain insights into the dependence of transport on nanoparticle properties, two separate parameters were measured: the number of nanoparticles that fully cross the BBB and the number that remain associated with the endothelium. Association of nanoparticles with the brain endothelium was substantially impacted by their physical characteristics. Hard particles associate more with the endothelium compared to soft particles, as do small particles compared to large particles, and spherical particles compared to rod-shaped particles. Transport across the BBB also exhibited a dependence on nanoparticle properties. A nonmonotonic dependence on size was observed, where 200 nm particles exhibited higher BBB transport compared to 100 and 500 nm spheres. Rod-shaped particles exhibited higher BBB transport when normalized by endothelial association and soft particles exhibited comparable transport to hard particles when normalized by endothelial association. Tuning nanoparticles' physical parameters could potentially enhance their ability to cross the BBB for therapeutic applications. K E Y W O R D S

Microfluidic cellular models, commonly referred to as “organs‐on‐chips,” continue to advance the field of bioengineering via the development of accurate and higher throughput models, captivating the essence of living human organs. This class of models can mimic key in vivo features, including shear stresses and cellular architectures, in ways that cannot be realized by traditional two‐dimensional in vitro models. Despite such progress, current organ‐on‐a‐chip models are often overly complex, require highly specialized setups and equipment, and lack the ability to easily ascertain temporal and spatial differences in the transport kinetics of compounds translocating across cellular barriers. To address this challenge, we report the development of a three‐dimensional human blood brain barrier (BBB) microfluidic model (μHuB) using human cerebral microvascular endothelial cells (hCMEC/D3) and primary human astrocytes within a commercially available microfluidic platform. Within μHuB, hCMEC/D3 monolayers withstood physiologically relevant shear stresses (2.73 dyn/cm 2 ) over a period of 24 hr and formed a complete inner lumen, resembling in vivo blood capillaries. Monolayers within μHuB expressed phenotypical tight junction markers (Claudin‐5 and ZO‐1), which increased expression after the presence of hemodynamic‐like shear stress. Negligible cell injury was observed when the monolayers were cultured statically, conditioned to shear stress, and subjected to nonfluorescent dextran (70 kDa) transport studies. μHuB experienced size‐selective permeability of 10 and 70 kDa dextrans similar to other BBB models. However, with the ability to probe temporal and spatial evolution of solute distribution, μHuBs possess the ability to capture the true variability in permeability across a cellular monolayer over time and allow for evaluation of the full breadth of permeabilities that would otherwise be lost using traditional end‐point sampling techniques. Overall, the μHuB platform provides a simplified, easy‐to‐use model to further investigate the complexities of the human BBB in real‐time and can be readily adapted to incorporate additional cell types of the neurovascular unit and beyond.

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Treatment of brain-related diseases is challenging due to the presence of the blood-brain barrier (BBB), a hurdle that prevents most foreign matter from entering the brain. While macromolecules and nanoparticles represent an increasing fraction of the therapeutic landscape in general, their limited ability to cross the BBB has hindered their clinical impact in treating diseases of the central nervous system. Here the various routes for entry of macromolecular therapeutics into the brain are discussed, as well as the methods used to enhance their transport. Particular emphasis is placed on highlighting quantitative trends and mechanistic insights into how the macromolecular transport can be improved, discussing novel enhancement strategies, and identifying areas in need of more detailed investigations. Overall, this review shows several promising advances and continued progress towards a more complete understanding of how macromolecule and nanoparticle design and delivery strategy characteristics can be leveraged to improve the treatment of brain diseases.

Infrared (IR) shielding materials are commonly used for different applications, such as smart windows or optical filters. Infrared radiation is responsible for about 50% of the energy coming from the sun. During a hot summer or cold winter a lot of energy is needed to keep the optimal temperature inside buildings and means of transport. To reduce the heat transmission and save energy IR shielding materials can be used as coatings made of polymer composites. Graphene oxide (GO) and its reduced forms have interesting IR absorption properties and might be used as a filler in a polymer matrix for IR shielding applications. Graphene oxide can be reduced by different methods. Depending on the reduction method reduced graphene oxide (rGO) with a different content of oxygen can be obtained exhibiting different properties. In this work we propose new polymer nanocomposites with poly(vinyl alcohol) as the matrix and 0.1 wt.% addition of graphene materials with different oxygen content to be used for IR shielding applications. The results show that the properties of the graphene filler strongly influence the infrared shielding properties of the obtained nanocomposites. The best IR shielding properties were obtained for the composites where rGO with the lowest oxygen content was used.