Microfluidic directed self-assembly of liposome-hydrogel hybrid nanoparticles.
We present a microfluidic method to direct the self-assembly of temperature-sensitive liposome-hydrogel hybrid nanoparticles. Our approach yields nanoparticles with structural properties and highly monodisperse size distributions 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 a photopolymerizable N-isopropylacrylamide mixture in aqueous buffer) to form nanoscale lipid vesicles with encapsulated hydrogel precursors. These precursor nanoparticles were collected off-chip and were irradiated with ultraviolet (UV) light in bulk to polymerize the nanoparticle interiors into hydrogel cores. Multiangle laser light scattering in conjunction with asymmetric flow field-flow fractionation was used to characterize nanoparticle size distributions, which spanned the approximately 150 to approximately 300 nm diameter range as controlled by microfluidic mixing conditions, with a polydispersity of approximately 3% to approximately 5% (relative standard deviation). Transmission electron microscopy was then used to confirm the spherical shape and core-shell composition of the hybrid nanoparticles. This method may be extended to the directed self-assembly of other similar cross-linked hybrid nanoparticle systems with engineered size/structure-function relationships for practical use in healthcare and life science applications.
Hong
Jennifer S
JS
Semiconductor Electronics Division, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA. Jennifer.hong@nist.gov
Stavis
Samuel M
SM
DePaoli Lacerda
Silvia H
SH
Locascio
Laurie E
LE
Raghavan
Srinivasa R
SR
Gaitan
Michael
M
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008027:Light; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D044085:Microfluidics; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D012542:Scattering, Radiation
D008081:Liposomes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate