Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 67

of lymph flowing through different elements of the lymphatics. The action of other
lymphotropic contrast media is based primarily on their active uptake by the nodal
macrophages (i.e., lymph nodes become visible only after the concentration of the
medium in the lymph node has achieved certain threshold value, which usually
requires prolonged periods of time). similar experiments with pEg-pE mixed
micelles with a core-incorporated amphiphilic 111 in- or gd-loaded pAp have also
demonstrated fast and efficient gamma and mr visualization of different compart-
ments of the lymphatic system. micelles mostly stay within lymph fluid rather than
accumulate in the nodal macrophages (because of protective effect of surface pEg
fragments) and rapidly move via the lymphatic pathway. They can serve as fast and
efficient lymphangiographic agents for scintigraphy or mri.
Blood pool imaging is of special interest for the evaluation of the current state of
blood flow and for the discovery of irregularities caused by atherosclerotic lesions,
thrombi, or tumors. Blood pool imaging requires prolonged circulation of contrast
agents and is usually based on the utilization of sterically protected polymer-modified
microparticulates with contrast properties.
CT represents an imaging modality with high spatial and temporal resolution.
The diagnostic value of CT might be further significantly increased when contrast
agents (i.e., substances containing X-ray absorbing heavy elements, such as iodine)
are used to attenuate tissues and organs of interest. since, as was already told,
providing diagnostically acceptable imaging requires the iodine concentration on the
order of millimoles per milliliter of tissue [139], large doses of low-molecular-weight
CT contrast agent, such as iodine-containing organic molecules, are normally admin-
istered to patients. in order to more specifically target contrast agents, attempts have
been made to use contrast agent-loaded microparticulate carriers for CT imaging [57,
140]. However, currently suggested particulate contrast agents possess relatively
large particle size (between 0.25 and 3.5 µm) and are actively cleared by phagocy-
tosis. Thus, in order to prepare a material whose distribution is limited to the blood
pool, certain simple properties seem necessary to be met: a size larger than fenes-
trated capillaries (>10 nm), resistance to phagocytosis, and the radiopaque moiety
structurally incorporated within the particulate.
Amphiphilic polymers which are able to spontaneously form stable and long-cir-
culating 10-80 nm micelles in an aqueous media seem to be carriers of choice that
meet all the aforementioned requirements [141]. The synthesis and in vivo properties
of a block copolymer of methoxy-poly(ethylene glycol) (mpEg) and iodine-substi-
tuted poly-l-lysine have been described [142, 143]. This copolymer easily micellizes
in the solution forming stable and heavily iodine-loaded particles (up to 35% of
iodine by weight) with a size well below 100 nm. The iodine content in these micelles
is about 30-35% of total weight. other amphiphilic polymeric micelles formed by
block copolymers have sizes around 10-50 nm [144, 145]. The slightly increased
particle size of mpEg-iodolysine micelles may be explained by noncovalent binding
of triiodobenzoic acid to the core of the micelle.
In vivo , the iodine-containing polymeric micelles demonstrated prolonged
circulation time [138], where iV injections into rats and rabbits and the X-ray signal
were monitored from several organs using a CT scanner. A significant enhancement