Doxil — The First FDA-Approved Nano-Drug: From an Idea to a Product - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 337

Direct work on Doxil development was initiated in Israel and
the USA 7.5 years earlier; however, the history of Doxil goes back
to 1979, when Alberto Gabizon and I started collaborating on the
development of liposomes as a drug delivery system of cytotoxic
drugs for the treatment of cancer. This idea stems from Paul Ehrlich's
(1906) classical “magic bullet” working hypothesis that by targeting
the desired drug to the diseased tissue, the “therapeutic index” (ratio)
and “the protective ratio” of the drug (for definitions see Wikipedia)
should be significantly increased by either improving therapeutic
efficacy or lowering toxicity, and preferably by combination of both.
The overall eff ect is the improvement of drug therapeutic eff ects.
Liposomes were proposed as a good option for a drug delivery
system (DDS) by Alec Bangham already in the 1960s, soon after he
described liposomes as an excellent model system for biological
membranes in 1964 (for historical perspectives, see Barenholz,
1992; Bangham, 1993; Lasic, 1996).
However, in 1979, 15 years after liposomes' first description
by Bangham (rev. in Bangham, 1993), the use of liposomes as a
drug delivery system was still in its infancy. When, on January 4,
2011, I searched in Delphion, which covers all patents and patent
applications (granted and pending), I found that until January 1979,
mention of liposomes anywhere in the text of the patents (including
background) was only 170 times, whereas in the claims (protected),
liposomes were referred to only 33 times. Today the situation is much
diff erent. Anywhere in the patents' text (including background),
liposomes are mentioned 224,836 times and in the patents' claims
(protected), liposomes are referred to 19,210 times.
Similar diff erences exist regarding scientific publications,
comparing less than 1200 publications that involved liposomes in
January 1979, while today more than 0.1% of all scientific papers
published in life and health sciences involve liposomes. As of this
writing (April 4, 2011), Doxil has more than 171,000 Google
citations.
Despite the poor and minimal information available on liposomes
as a DDS in 1979, Gabizon and I selected liposomes as our preferred
DDS. Our decision was based on the common knowledge at that time,
which can be summarized as follows:
• Liposomes can act as a reservoir of both hydrophilic and
amphipathic low- and high-molecular-weight drugs/agents.