Doxil — The First FDA-Approved Nano-Drug: From an Idea to a Product - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 364

liposomes with prolonged circulation time and RES avoidance were
termed by Dr. Frank Martin of LTI “Stealth ® ” liposomes and these
unique properties of liposomes were referred to as “Stealthness,”
which means unseen or unrecognized as particulates by the RES.
At the same time, I and my student Gilad Haran (now a professor
at the Weizmann Institute) were working on the development of a
remote and stable loading method for doxorubicin, which should
enable the formulation to reach sufficient level of drug to achieve
therapeutic efficacy in humans under conditions that the drug when
reaching the tumor will be bioavailable to the tumor cells (Barenholz
and Haran, 1993, 1994; Haran et al., 1993).

12.4.3 Liposomes Having Prolonged Blood Circulation

In 1987 when I came back to Jerusalem after one and a half years
of sabbatical at LTI, Alberto Gabizon just started his sabbatical
with Dimitri Papahadjopoulos at USCF. Each of us started to
work on diff erent aspects related to how to achieve an improved
liposomal doxorubicin formulation. Alberto focused his studies on
how to prolong blood circulation of liposomes while I focused on
how to achieve stable high drug loading into liposomes and nano-
liposomes. During his sabbatical, Alberto worked, with LTI support
and blessing, on liposome formulations with extended circulation
time. Terry Allen at the University of Alberta was the first one to
describe such formulations (Allen and Chonn, 1987; Allen, 1989,
US patent 4,837,028). In 1986, we, at LTI, decided to support her
research on this issue. LTI scientists looked also for long-circulating
liposomal formulations of various lipid compositions that diff ered
from those studied by Allen and Gabizon. The latter two scientists
added known (but not frequently used) lipids to the liposome
lipid composition in order to reach extended circulation time and
selective tumor localization with the focus on gangliosides (Allen) or
hydrogenated phosphatidylinositol, abbreviated as HPI (Gabizon).
LTI scientists tried and studied novel lipids that were not recognized
as known natural lipid species (Woodle et al., 1991; Woodle et al.,
1990, rev. in Woodle and Lasic, 1992; Woodle, 1993). All these
three groups (associated with LTI) worked in parallel on diff erent
formulations and all were using small unilamellar liposomes with
narrow unimodal size distribution having a mean size of ~100
nm. These nano-liposomes were prepared by medium pressure