Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 58

evident success in the development of antibody-to-nanovesicle coupling technique
and improvements in the targeting efficacy, the majority of antibody-coupled
nanovesicles still ended in the liver, which was usually a consequence of insufficient
time for the interaction between the target and targeted nanocarrier. This is especially
true in cases when a target of choice has diminished blood supply (ischemic or
necrotic areas), and only a small number of nanovesicles passes through the target
with the blood during the time period when nanovesicles are present in the circulation.
The same lack of targeting occurs if the concentration of the target antigen is very
low and the number of “productive collisions” between target antigens and immuno-
nanocarrier is too small. in both cases, much better accumulation can be achieved if
the nanovesicles can stay in the circulation long enough. This will increase the total
quantity of immunocarrier passing through the target and the number of collisions
between the immunocarrier and target antigen [61].
different methods have been suggested to achieve long circulation, including
coating the nanocarrier lipid surface with inert, biocompatible polymers, such as
pEg, which form a protective layer over the nanocarrier surface and slow down the
nanocarrier recognition by opsonins and subsequent clearance. Long-circulating
nanocarriers are now widely used in biomedical in vitro and in vivo studies and even
found their way into clinical practice [62]. The use of pEgylated liposomes and
micelles as carriers for contrast agents also forms now an important area of research
[5, 43, 63]. Very special pharmacokinetic properties of long-circulating (usually
pEgylated) drugs and drug carriers deserve at least a short separate discussion.
3.2.7 pharmacokinetics and clearance of Long-circulating drugs
and drug carriers
The most important pathways for the clearance of long-circulating drugs and drug
carriers—extravasation, renal clearance, and uptake by cells from the blood—are
independent processes. However, namely, extravasation determines interstitial and
lymphatic transport and interstitial and lymphatic uptake of long-circulating sub-
stances. With this in mind, it was suggested to divide all long-circulating drugs/
carriers into extravasating and nonextravasating ones [64]. The main difference
between these two groups is their size, with a border zone being at about 5-10 nm.
The nonextravasating group includes cells, cell ghosts, particles, and large nanoves-
icles, while the extravasating group includes small nanovesicles, proteins and their
derivatives (including antibodies and pEg-modified enzymes), and various polymers
that are large enough (more than 40 kda) to avoid fast renal clearance [65]. in certain
pathological areas with increased endothelial permeability, the pattern can change
completely. However, such conditional division permitted to build idealized models
describing the biological behavior of long-circulating substances [64].
interactions of nonextravasating or very slowly extravasating drugs/carriers are
limited to blood components and cells exposed into the blood. usually, such sub-
stances are removed from the circulation via opsonization-mediated phagocytosis,
and surface coating with pEg or pEg-like polymers may prevent opsonization or, at
least, significantly slow it down.