We present a microfluidic method to direct the self-assembly of liposome-hydrogel hybrid nanoparticles. Our approach yields nanoparticle size distributions that are highly monodisperse and precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. We used microfluidic hydrodynamic focusing to control the convective-diffusive mixing of two miscible nanoparticle precursor solutions (a DPPC:Cholesterol:DCP phospholipid formulation in isopropanol, and an N-Isopropylacrylamide mixture in aqueous buffer) to form nanoscale lipid vesicles with encapsulated hydrogel precursors. Following on-chip synthesis, we UV-irradiated these precursor nanoparticles off-chip to polymerize the nanoparticle interiors into hydrogel cores. To characterize the resulting hybrid nanoparticle system, we first used asymmetric flow field-flow fractionation in conjunction with multi-angle laser light scattering to determine nanoparticle size distributions, which spanned the ≈150 to ≈300 nm diameter range as controlled by microfluidic mixing conditions, with a polydispersity of ≈3 % to ≈5 % (relative standard deviation). We then used transmission electron microscopy to qualitatively characterize the shape and composition of the hybrid nanoparticles. We believe that our method may be extended to the directed self-assembly of other soft matter hybrid nanoparticle systems of current interest.
Pub Type: Journals
liposome, hydrogel, nanoparticle, microfluidic, self-assembly, hybrid