This study is about fine tuning the targeting capacity of peptide-decorated nanoparticles to discriminate between cells that express different integrin make-ups. Using microfluidic-assisted nanoprecipitation, we have prepared poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles with a PEGylated surface decorated with two different arginine-glycine-aspartic acid (RGD) peptides: one is cyclic (RGDFC) and has specific affinity towards α_vβ₃ integrin heterodimers; the other is linear (RGDSP) and is reported to bind equally α_vβ₃ and α₅β₁. We have then evaluated the nanoparticle internalization in two cell lines with a markedly different integrin fingerprint: ovarian carcinoma A2780 (almost no α_vβ₃, moderate in α₅β₁) and glioma U87MG (very high in α_vβ₃, moderate/high in α₅β₁). As expected, particles with cyclic RGD were heavily internalized by U87MG (proportional to the peptide content and abrogated by anti-α_vβ₃) but not by A2780 (same as PEGylated particles). The linear peptide, on the other hand, did not differentiate between the cell lines, and the uptake increase vs. control particles was never higher than 50%, indicating a possible low and unselective affinity for various integrins. The strong preference of U87MG for cyclic (vs. linear) peptide-decorated nanoparticles was shown in 2D culture and further demonstrated in spheroids. Our results demonstrate that targeting specific integrin make-ups is possible and may open the way to more precise treatment, but more efforts need to be devoted to a better understanding of the relation between RGD structure and their integrin-binding capacity.

Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL⁻¹ of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF) or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with M_n ranging from ~9700 to 16,000 g·mol⁻¹ and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL⁻¹ fluconazole and 1.5 mg·mL⁻¹ copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.

An experimental study of the displacement of one immiscible fluid by another was performed in microchannels with circular, square and near‐semicircular cross‐sections, with hydraulic diameters from 100 to 200 μm. Experiments were performed over a range of capillary number, Ca, from 0.02 < Ca < 80, with viscosity ratios between the two fluids ranging from 20 to 100. The liquid film left on the channel wall following the advance of the displacing fluid was obtained from visual measurements and a method for the estimation of mean film thickness was shown to be in good agreement with existing correlations. The addition of a surfactant (Sodium Dodecyl Sulfate, SDS) dissolved in the displacing fluid led to a reduction in the thickness of the residual film. © 2018 The Authors AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers AIChE J, 64: 3456–3466, 2018