Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 49

to various pathological tissues and into target cells in particular, via various targeting
ligands and homing moieties [16].
Analogously, micellar assemblies, including lipopolymeric micelles, represent
another promising type of pharmaceutical carriers. micelles are amphiphilic com-
pound-formed colloidal particles with hydrophobic core and hydrophilic corona with
size range between 5 and 100 nm [17], with exceptional capability to enhance the
solubility and bioavailability of poorly soluble pharmaceuticals [18]. The use of
certain amphiphilic molecules, such as polyethylene glycol (pEg)-phosphatidyleth-
anolamine (pE), as micelle-building blocks can extend the blood half-life of the
micellar carrier. in addition, the micelles could be combined with different targeting
ligands, strategically incorporated into the micelle structure to make micelles tar-
geted. There are several main micelle parameters (size, critical micelle concentration
(CmC), and loading capacity of the hydrophobic core of the micelle) essential for
successful preparation of micelle-incorporated pharmaceuticals and imaging agents
[19]. As a rule, these parameters are as follows: the size of a pharmaceutical micelle
is between 10 and 100 nm, an optimal CmC value is below micromolar concentration,
and the loading efficiency toward a hydrophobic drug is between 5 and 25 wt.%. in
the case of targeted micelles, the release of a free drug from micelles limited to the
target organ should lead to the increased efficacy of the drug, while maintaining sta-
bility of the micelles in the blood should contribute to drug solubility and toxicity
reduction due to minimal interaction with nontarget organs [14, 18].

3.2 geNeraL approaches for LoadiNg Liposomes
aNd miceLLes with coNtrast ageNts

regardless of the imaging modality to be employed, lipid-based nanoformulations,
namely, liposomes and micelles, have been long studied as vehicles for contrast
agents to facilitate sufficient accumulation of contrast agent within the required area
of interest, in order to differentiate this area from surrounding tissue. Table 3.1 shows
the reporter groups and their minimal required concentration at area of interest,
which have to be attained, for each particular case.
one can easily recognize that different chemical nature of reporter moieties uti-
lized in different imaging modalities requires different protocols to load liposomes
and micelles with a certain contrast agent. in addition, all the imaging modalities
exemplified here differ not only in their sensitivity and resolution, but for appropriate

taBLe 3.1 concentration of a contrast agent required for diagnostically
significant tissue attenuation in various imaging modalities

required tissue
concentration (m)

modality reporter group

gamma-scintigraphy radionuclide ( 111 in, 99m Tc) 10 −10

mri paramagnetic metal (gd, mn) 10 −4

CT imaging Heavy element (iodine, bromine, barium) 10 −2