Detection and Description of Tissue Disease: Advances in the Use of Nanomedicine for Medical Imaging - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 247

glycol (PEG), which also reduces interactions with the RES and is
chemically well defined, as well as being much less expensive than
GM1. While PEG does reduce opsonization, there is evidence that
PEG-coated liposomes still induce a complement-based immune
response [9].
A range of sizes of PEG has been evaluated. With higher MW PEGs
(e.g., 5 kDa) there is steric hindrance of the ability of ligands attached
to the liposome to bind to their targets [10], while for lower MW PEGs
(e.g., 750 Da) the circulation time is shorter [11], leading to use of
PEGs in 2 kDa range. Alternatively, the targeting ligand, which could
be an antibody, peptide, or other targeting molecule, can be attached
to the PEG so that it is held outside the PEG coating, reducing steric
hindrance while simultaneously increasing circulation time [12].
Current methods of encapsulating small-molecule, water-soluble,
iodinated compounds in the liposome core still leave a significant
amount of contrast agent in the bulk formulation medium resulting
in uptake of the non-encapsulated material in the kidney shortly
after injection. This can confound quantitative studies as it suggests
a triphasic clearance of the nanoparticle or a faster initial clearance
phase than is actually the case. However, the presence of this excess
material in the bulk formulation solution has the advantage of
reducing the rate of loss of the contrast agent from the core of the
nanoparticle in vitro , which results in a longer shelf life and more
consistent imaging results [13]. This problem arises because the
rate of loss of the iodinated contrast agent from the liposome core
is related to the concentration diff erence across the lipid bilayer
and also to the osmotic pressure diff erence. This can be avoided by
using the iodinated-polymer method where the iodine is covalently
bound to the lipid itself, eff ectively precluding loss of the iodine
from the liposome. Another approach to avoiding this problem was
discussed by Wei et al [14] who developed a multilamellar (rather
than unilamellar) liposomal construct. This had the advantage of
entrapping high concentrations of iodohexol (50 mg/ml) within
the liposomal core while reducing the loss of the iodine by diff usion
through the bilayer. A further development of this approach was
reported by Kweon et al . [15], who used a mixture of water-soluble
and oil-based iodinated compounds. The water-soluble material
is trapped in the hydrophilic core while the oil-based material is
trapped in the hydrophobic bilayer, resulting in a significant increase
in radioopacity in the target organ. Encapsulating iopamidol, a