posted on 2019-10-01, 20:46authored byZahraa
S. Al-Ahmady, Roberto Donno, Arianna Gennari, Eric Prestat, Roberto Marotta, Aleksandr Mironov, Leon Newman, M. Jayne Lawrence, Nicola Tirelli, Marianne Ashford, Kostas Kostarelos
Hybrids
composed of liposomes (L) and metallic nanoparticles (NPs)
hold great potential for imaging and drug delivery purposes. However,
the efficient incorporation of metallic NPs into liposomes using conventional
methodologies has so far proved to be challenging. In this study,
we report the fabrication of hybrids of liposomes and hydrophobic
gold NPs of size 2–4 nm (Au) using a microfluidic-assisted
self-assembly process. The incorporation of increasing amounts of
AuNPs into liposomes was examined using microfluidics and compared
to L–AuNP hybrids prepared by the reverse-phase evaporation
method. Our microfluidics strategy produced L–AuNP hybrids
with a homogeneous size distribution, a smaller polydispersity index,
and a threefold increase in loading efficiency when compared to those
hybrids prepared using the reverse-phase method of production. Quantification
of the loading efficiency was determined
by ultraviolet spectroscopy, inductively coupled plasma mass spectroscopy,
and centrifugal field flow fractionation, and qualitative validation
was confirmed by transmission electron microscopy. The higher loading
of gold NPs into the liposomes achieved using microfluidics produced
a slightly thicker and more rigid bilayer as determined with small-angle
neutron scattering. These observations were confirmed using fluorescent
anisotropy and atomic force microscopy. Structural characterization
of the liposomal–NP hybrids with cryo-electron microscopy revealed
the coexistence of membrane-embedded and interdigitated NP-rich domains,
suggesting AuNP incorporation through hydrophobic interactions. The
microfluidic technique that we describe in this study allows for the
automated production of monodisperse liposomal–NP hybrids with
high loading capacity, highlighting the utility of microfluidics to
improve the payload of metallic NPs within liposomes, thereby enhancing
their application for imaging and drug delivery.