Detection and Description of Tissue Disease: Advances in the Use of Nanomedicine for Medical Imaging - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 244

low cost and minimal toxicity, a third research focus is the evaluation
of radiodense elements other than iodine (e.g., barium).

8.2.1 Macromolecular Contrast Agents

To address the problem of increasing the time available for imaging,
the most straightforward approach is to increase the size of the
contrast agent to the nanoparticle range (typically 1-100 nM), which
slows its clearance from the blood (for more detailed discussion, see
Hallouard et al . [1]). If one adopts this approach, the choices that
must be made are: (1) What type of nanoparticle to use and how this
choice aff ects the particle's in vivo behavior, (2) What radiopaque
element will be used and how will it be attached to the nanoparticle,
and (3) What other steps are required for in vivo use? In terms of
which nanoparticle is optimal, there has been a progression in the
field from use of the relatively simple micelles, to more complex but
also more efficacious liposomes, to dendrimers, and finally to the
use of microcrystalline or particulate forms of radiopaque elements.
We will consider each of these in turn.

8.2.1.1 Micelles

Micelles are single-layer vesicles that form spontaneously in
surfactant solutions when the surfactant concentration exceeds
the critical micelle concentration (CMC). The CMC varies with the
surfactant, so the materials used in the manufacture of intravenously
administered micellar drugs must be chosen so that the CMC is low
enough that the micelle does not collapse when the drug is diluted
upon injection, achieving the desired goal of remaining intact in the
circulatory system for a prolonged period of time.
Micelles can be used as contrast agents in two ways: The micelle
can be used as a carrier, with the radiopaque element transported in
the hydrophobic core of the micelle, or the radiopaque element can
be covalently attached to the polymer constituents of the micelle, to
either the hydrophilic outer “head” or the hydrophobic inner “tail.”
Covalent attachment of the radiopaque element to the constituents
of the micelle is ideal as it improves retention of the element by the
micelle, increasing specificity, and also reducing toxicity.
For a micellar CT contrast agent to be eff ective, it must deliver
sufficient mass of the radiopaque element to the tissue of interest