Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 55

with conventional preparations at the same phospholipid content. in addition to the
enhanced relaxivity, the pEg polymer attached on liposomal or micellar carriers can
help in avoiding the contrast agent (both for gamma-imaging and mri) uptake in the
site of injection by resident phagocytic cells.
Nanocarriers loaded with 111 in via the membrane-incorporated pAp demon-
strated significantly higher labeling efficiency than nanocarriers loaded with 111 in
via the monomeric dTpA-pE (fig. 3.2, panel B). This technique allowed to increase
the number of bound reporter metal atoms per vesicle and to decrease the dosage
of an administered total liposomal lipid without compromising the image signal
intensity [46].

3.2.5 aqueous phase Loading of preformed Nanocarrier

several methods have been developed for loading the radioisotope into the aqueous
phase of preformed nanocarriers. This approach generally uses lipophilic chelator
capable of carrying the radioisotope through the lipid membrane into the aqueous
phase, where the isotope is rechelated into a more firm complex with an entrapped
compound and remains inside the nanocarrier. The success of this method depends
mainly on the high affinity of the radioisotope for the agent entrapped in the aqueous
phase of the nanocarrier. otherwise, the radioisotope will shuttle back and forth
across the lipid membrane. This method has shown high labeling efficiency (more
than 90%). moreover, it is likely to have the greatest in vivo stability, because of the
protected location of the radioisotope inside the nanocarrier [26].
initially, the approach was demonstrated with 67 ga transported through the lipo-
somal bilayer as the lipophilic 67 ga-oxine complex and then irreversibly trapped
inside nanocarriers via the presence of aqueous interior-loaded hydrophilic chelator
in preformed nanocarriers [47]. The same procedure was suggested for labeling
nanocarriers with 111 in as well [48]. in the last decade, two reproducible methods of
labeling postmanufactured nanocarriers with 99m Tc have been reported. in the first
method, 99m Tc is chelated into the lipophilic carrier hexamethylpropyleneamine
oxime (HmpAo) [49]. The 99m Tc-HmpAo complex is then added to nanocarriers
with encapsulated glutathione (gsH) and incubated with the gsH-containing nano-
carriers for 30 min, during which the 99m Tc-HmpAo migrates across the lipid mem-
brane inside nanocarriers, where it is converted to a hydrophilic complex by reductive
partial decomposition via the interaction with gsH. The hydrophilic 99m Tc-HmpAo
complex remains trapped within the nanocarrier. This method proved reliable, yield-
ing in vivo stable radiolabeled nanocarriers with high labeling efficiency (~85%).
in a similar way, suresh et al . proposed the use of the hepatobiliary imaging agent
99m Tc-diisopropyl iminodiacetic acid ( 99m Tc-disidA) to label preformed nanocarri-
ers with encapsulated gsH [50]. As in the previously mentioned study, the 99m Tc-
disidA complex undergoes the reductive decomposition to more hydrophilic
species via the reaction with encapsulated gsH, yielding the incorporation of the
99m Tc-disidA into the nanocarriers with 90% efficiency. The labeled nanocarriers
were stable in saline and 90% fBs for up to 24 h. Biodistribution studies in mice