Design and Development of Theranostic Nanomedicines - Nanotechnology for Biomedical Imaging and Diagnostics - page 437

strategies in nanoemulsion-based theranostics, the targeting agent is attached to the
droplet surface by covalent conjugation to the surfactant molecule. For example, pFC
nanoemulsions targeted to α v β 3 integrins for atherosclerosis imaging have been
developed [131]. in an earlier study, lanza et al . reported the targeted delivery of
antiproliferative drugs to smooth muscle cells using perfluorooctyl bromide (pFoB)
nanoemulsions [132]. The pFoB nanoemulsion lipid outer layer incorporated bioti-
nylated phosphatidylethanolamine and tissue factor-specific antibody attached to the
surface by using avidin. The hydrophobic drugs DoX and taxol were introduced to
the formulation by adding them to the surfactant comixture prior emulsification.
nanoemulsions are prepared by high-pressure homogenization, high energy
processing (e.g., microfluidization and sonication), and low energy emulsification
methods, such as phase inversion temperature (piT) and concentration (piC)
methods [133]. Typical nanoemulsions are oil-in-water emulsions (o/W) with one or
two surfactants to stabilize the dispersed phase. recently, our group reported novel
triphasic nanoemulsions (fluorocarbon/hydrocarbon/water, F/h/W), which contain
two immiscible oils (F and h) as the dispersed phase stabilized by surfactants [3, 134].
nanoemulsions show remarkable kinetic stability as demonstrated recently by
combination of static and dynamic neutron scattering analyses [135]. Due to their
small droplet size, nanoemulsions are translucent and typically resistant to cream-
ing and sedimentation. They do not require high amounts of surfactant and can be
stabilized by steric effects [106]. The most common degradation mechanism in
nanoemulsions is ostwald ripening, a gradual growth of the larger particles at the
expense of smaller ones by molecular diffusion. nanoemulsions can be produced
using microfluidization or high-pressure homogenization on larger industrial scale
reproducibly [136]. This last feature makes nanoemulsions very attractive systems
for theranostic nanomedicine development. They offer high carrying capacity for
imaging and therapeutic agents while being manufacturing friendly. For theranostic
formulations, nanoemulsions are typically prepared using high energy methods,
sonication, and microfluidization. sonication is an attractive method for small-scale
production in the laboratory due to its simplicity and ease of operation. however,
microfluidization shows superior performance in droplet size reduction, small poly-
dispersity, and potential for increased scale production. Therefore, microfluidization
in our view is the preferred method for nanoemulsification.
There are two ways of preparing drug-loaded imaging-capable nanoemulsions:
(1) direct entrapment and (2) conjugation. patel et al . recently demonstrated that
lipophilic drugs can be easily introduced into pFC nanoemulsion by dissolving them
into a hydrocarbon-solubilizing oil first, mixing with pFC, and emulsifying the mix-
ture by microfluidization [3]. earlier studies by Wickline et al . added drugs to lipid
surfactant commixture before the water phase was added and nanoemulsion was
subsequently produced by sonication or microfluidization [123]. There are also reports
of nonfluorinated theranostic nanoemulsions. in a recent study, o/W nanoemulsion
loaded with iron oxide nanocrystals for Mri, the fluorescent dye Cy7 for nirF
imaging, and the hydrophobic glucocorticoid prednisolone acetate valerate (pav) was
evaluated in a mouse tumor model. The nanoemulsion surface was decorated with
α v β 3 -specific rgD peptides for angiogenesis targeting. in the study, both imaging