Doxil — The First FDA-Approved Nano-Drug: From an Idea to a Product - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 357

very similar to that of free doxorubicin. Thus, although the toxicities
of free DOX and OLV-DOX diff er somewhat quantitatively, they are
qualitatively very similar.
Liver tumor
remain unlabeled
Figure 12.4 Liver scintigraphies 2 h after injection of patient with
radiolabeled 111 In-OLV or 99 Tc-colloid (Gabizon et al., 1991).
The “bottom line” conclusions of our human clinical trials
are based on the PK and BD human study in which the results of
clearance of drug and the liposomes (DOX and liposome PG) are
combined with the results of the radiolabeled 111 In-OLV human
imaging experiment. The latter clearly indicates that in humans
who retain significant liver function, the OLV accumulate in the liver
and spleen RES, but without reaching the liver tumor. What is more
problematic is that there is a fast dilution-induced drug release of
the OLV-DOX in the blood already during the i.v. infusion. This means
that in humans, the liposomes reaching the liver are almost drug free,
so our basic working hypothesis that the RES will act as a drug depot
is not valid for human treatment. Another important conclusion is
the confirmation that in humans severe liver dysfunction will have
a large eff ect on RES-directed liposomes; then more liposomes will
reach the spleen and the bone marrow, and drug leakage of the
circulating liposomes will become the main factor that determines
drug fate.