Biomedical Engineering Reference
In-Depth Information
of these systems are. The most striking advantage is their surface
multivalency. In addition, these systems are relatively monodisperse
and are of defined shape, usually globular. Geng et al. [152] studied
filomicelles (long filamentous stable diblock copolymeric micelles of
PEG-polyethylethylene or PEG-polycaprolactone) and showed that
filament structures persist in circulation after intravenous injection
considerably longer than rigid rods ( λ -phages) and flexible spheres
(“stealth” polymersomes). Filomicelles of varied length loaded with
paclitaxel shrank A549 tumors in nude mice, with greater efficacy
for longer filomicelles (up to 8 μm). They attributed this to the
nanoparticles behavior under flow; spherical and short filaments are
readily taken up by cells, while flexible long filaments are extended
by the flow and flow past the cells. Under static conditions, long
filaments are relaxed and internalized by cells. Thus the elongated
filament shape, as well as filament flexibility, makes it a better
delivery system. These in vitro experiments were conducted under
flow velocity similar to that in the spleen. It should be interesting
to conduct similar experiments under conditions resembling the
sluggish flow of tumor vasculature. This may shed more light on
physical mechanisms leading to the EPR eff ect. Saad et al. [153]
conducted a comparative efficacy study of various drug nanocarriers.
They used 30 nm linear PEG polymer, 5 nm PAMAM dendrimer, and
100 nm liposome to deliver paclitaxel to H69 and A549 lung cancer
cells and tumors on nude mice. All nanocarriers were marked
with Cy5.5 and a synthetic analog of LHRH peptide was attached
for targeting. They found that all nanocarriers showed enhanced
efficacy compared with the free drug. Without the targeting LHRH
peptide, dendrimeric nanocarrier was the least eff ective, while PEG
polymer nanocarrier was the most eff ective in suppressing tumor
growth. This result correlates well with Geng et al. [152] theorem
of better efficacy for long flexible filaments as nanocarriers. The
most surprising result of Saad et al. [153] was received when adding
targeting moieties to these nanocarriers. Targeting with LHRL
peptide significantly enhanced anti-tumor activity of all nanocarriers
and leveled down the diff erences between them. This suggests that
when using eff ective targeting, nanocarriers can be selected based
on parameters such as type of therapeutic, solubility, electric charge,
ease of preparation, etc., rather than architectural parameters such
as size and shape.
 
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