Biomedical Engineering Reference
In-Depth Information
world that were “fed” by the same available scientific information
were working in parallel to us on the development of similar systems
(see below).
As described above, the 1980s were problematic for the field of
liposome medical applications. Nevertheless, it was an exciting time
for the development of liposomal drugs as three startup companies
were founded in the United States alone, Vestar at Pasadena, CA,
The Liposome Company (TLC) at Princeton, NJ, and Liposome
Technology Inc. (LTI) at Menlo Park, CA; none of them survived.
Although support money was short, these companies succeeded to
initiate, and later in the 1990s, when money became more available,
to develop most of the FDA-approved liposomal drugs. Interestingly,
all three companies selected and had diff erent intellectual property
(I.P.) on liposomal anthracyclines as one of their leading products
[Doxil
®
of LTI (now sold by Johnson & Johnson, DaunoXome of
Vestar (now sold by Diatos), and Myocet
of TLC (now sold by Zenous
Pharma Sopherion Therapeutics)]. This clearly demonstrates that
these three leading (at that time) startup companies worked along
similar lines of thought.
12.2
First-Generation Liposomal Doxorubicin —
Liver-Directed Liposomal Doxorubicin
12.2.1 Background
The common knowledge available in 1980 on liposomes as drug
carriers (see above) suggests that liposomes should be mainly
useful to treat diseases that are localized at RES organs, which are
enriched with MPS activities. Therefore, we selected liver hepato-
cellular carcinoma as the tumor target of choice. This tumor type,
although not a major disease in the Western world, is the most
abundant tumor in Japan and a very common one in China. Our idea
was that the liposomes loaded with the drug will be cleared fast from
the circulation by the RES system and will be taken up efficiently
by the phagocytic cells, mainly in the liver. There the liposomes
were expected to reach and be processed at the phagosomes and
endosomes, followed by drug release to the cytoplasm. From there,
it can be further released to the circulation and become available
and kill the cancer cells that reside in the liver in proximity to the
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