Doxil — The First FDA-Approved Nano-Drug: From an Idea to a Product - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 362

that the development of liposomal doxorubicin is feasible. Therefore
we decided to look for an alternative liposomal doxorubicin
formulation that can overcome all the above deficiencies and will be
able to reach most metastatic solid tumors and will not be limited to
liver-residing tumors.
We decided that in order for the liposomes to become an
approved anticancer drug, the liposomes should be characterized by
the following features:
• They should be at the nano scale (nano-liposomes) so they
will be able to take advantage of the EPR eff ect and extravasate
from the blood vessels at the tumor into the tumor tissue.
• In order to be efficacious, the liposomes should reach the
tumors loaded with a therapeutically high enough drug level.
• The drug PK and BD should be controlled by the liposomes,
with the liposomal drug demonstrating a highly prolonged
plasma circulation time to give it the time needed to achieve
drug tumor accumulation.
• Drug should be available to tumor cells either by drug release
at the tumor site or by the drug loaded nano-liposomes being
internalized by the tumor cells.

12.4.2 Requirements to Achieve Therapeutically

Efficacious Passively Targeted Drug Loaded
Liposomes and Means to Fulfill Them

Table 12.2 summarizes the requirements to achieve therapeutically
efficacious passively targeted drug loaded liposomes and means to
fulfill them (based on Barenholz, 2007).

Table 12.2 Requirements to achieve therapeutically efficacious passively
targeted drug loaded liposomes and means to fulfill them

Requirements Solutions

1. Extended circulation time
in intact form in the human
plasma

Development of sterically stabilized
liposomes (SSL) composed of
high T m lipids, cholesterol, and a
lipopolymer such as 2000 PEG-DSPE