(594d) Synthesis of Biomimetic Oxygen-Carrying Compartmentalized Microparticles Using Flow Lithography

Bio-inspired polymeric particles engineered in the likeness of mammalian cells are promising vehicles for drug delivery and clinical diagnostics. Experiments have shown that biomimetic particles with controlled physical properties (i.e., size, shape, deformability and compartmentalization) can co-encapsulate incompatible actives, maneuver through biological barriers, avoid cellular capture, and even prolong circulation time or alter biodistribution patterns in vivo. Currently, a facile technique for patterning morphologically complex, compartmentalized microparticles down to the cellular length scale ( 10 microns) is still largely missing.

We report a microfluidic approach for lithographically photo-patterning compartmentalized microparticles with any 2D-extruded shape, down to the cellular length scale (~10 microns). The prepolymer solution consists of a UV crosslinkable perfluorodecalin-in-water nanoemulsion stabilized by Pluronic F-68. The nanoemulsions are generated using high-pressure homogenization and osmotically stabilized by the trapped species method. The presence of PFC droplets increases the solubility and diffusivity of oxygen in the prepolymer solution, thereby enhancing the rate of O₂ inhibition during microparticle synthesis. We develop a simple model that successfully predicts the augmented O₂ mass transport, which agrees well with experimental data. Informed by our analytical results, cell-sized composite microgels are generated by controlling the oxygen environment around the polydimethylsiloxane (PDMS) microfluidic synthesis device. These nanoemulsion composites are functionally similar to red blood cells as oxygen carriers. And importantly, in general, the ability to package hydrophobic nanodroplets within a hydrophilic gel network changes the presentation of the nanoemulsion: the physicochemical properties of the encapsulating gel may be readily tuned to introduce additional functionalities (e.g., conjugate ligands for targeted interactions) or dictate biodistribution pattern in vivo; and the kinetically arrested oil droplets can be used to encapsulate and release theranostic agents.