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Polymer nanoparticles (NPs), due to their small size and surface functionalization potential have demonstrated effective drug transport across the blood–brain–barrier (BBB). Currently, the lack of in vitro BBB models that closely recapitulate complex human brain microenvironments contributes to high failure rates of neuropharmaceutical clinical trials. In this work, a previously established microfluidic 3D in vitro human BBB model, formed by the self‐assembly of human‐induced pluripotent stem cell‐derived endothelial cells, primary brain pericytes, and astrocytes in triculture within a 3D fibrin hydrogel is exploited to quantify polymer NP permeability, as a function of size and surface chemistry. Microvasculature are perfused with commercially available 100–400 nm fluorescent polystyrene (PS) NPs, and newly synthesized 100 nm rhodamine‐labeled polyurethane (PU) NPs. Confocal images are taken at different timepoints and computationally analyzed to quantify fluorescence intensity inside/outside the microvasculature, to determine NP spatial distribution and permeability in 3D. Results show similar permeability of PS and PU NPs, which increases after surface‐functionalization with brain‐associated ligand holo‐transferrin. Compared to conventional transwell models, the method enables rapid analysis of NP permeability in a physiologically relevant human BBB set‐up. Therefore, this work demonstrates a new methodology to preclinically assess NP ability to cross the human BBB.

Nature's inspiration is a promising tool to design new biomaterials especially for frontier technological areas such as tissue engineering and nanomedicine.

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In the past, tripolyphosphate (TPP)‐crosslinked chitosan (CS) nanoparticles (CSNPs) have been widely applied for the delivery of biomacromolecules, because of their mild preparation conditions. However, poor uniformity and burst release limit their application to some extent. In this study, we investigated the effect of pH on the formation and on protein encapsulation efficiency (EE) of CSNPs. Results revealed that smaller particles are formed at lower pH and that the size distribution is conjointly influenced by pH and CS/TPP mass ratio. EE of bovine serum albumin (BSA) increased significantly with pH value. The influence of the pH of the crosslinker (TPP) solution was also studied, showing that CSNPs prepared with basic TPP solution (pH 9.5) had larger size, higher yield, and BSA EE compared with those obtained with acidic TPP solution (pH 5.5). Characterization by Fourier transform infrared‐attenuated total Reflectance (FTIR‐ATR) spectroscopy and SEM as well as the in vitro BSA release analysis revealed that the pH of the TPP solution might influence CSNPs' properties, by changing the conformation of polymer chains. This study analyzes the formation of CSNPs and protein encapsulation mechanisms at different pH values of both the polymer and the crosslinker solutions, suggesting strategies to overcome some of the major drawbacks of CSNPs as protein nanocarriers for therapeutic applications. POLYM. COMPOS., 34:1538–1545, 2013. © 2013 Society of Plastics Engineers