لخّصلي

APPLICATIONS OF LIPOSOMES IN
CANCER
Liposomes have been successfully used in
cancer therapy. Although, the application of
liposomes in the field of cancer therapeutics has
been extensively studied and deserves a broad
assessment but this is outside the scope of this
review. However, the most successful
applications of liposomes in cancer therapeutics
are discussed here. A number of different
liposomal formulations of anti-cancer agents
have been shown to deliver the drug at the site
of solid tumors with minimum toxicity as
compared to free drug (Allen and Cullis 2013;
Sutradhar and Lutful 2014).
Currently, there are a many products in the
market and in clinical development for use as
anti-cancer drug delivery vehicle (Allen and
Cullis 2013) (Table 1). Doxil, a PEGylated
liposomal formulation, is the first liposomal
product that was approved by the FDA for the
treatment of kaposi’s sarcoma in AIDS patients
(James et al. 1994; Barenholz 2012). Doxil
(US), or Caelyx (outside-US) is a PEGylated
liposomal formulation encapsulating anticancer
drug doxorubicin commercialized by Johnson &
Johnson. In 2011, an imbalance between the
demand and supply of Doxil was observed as the
manufacturing unit was shut down temporarily
due to some quality control issues (Berger et al.
2014; Chou et al. 2015). To address the Doxil
shortage in USA, FDA allowed temporary
importation of LipoDox. LipoDox is the same
liposomal formulation as Doxil in USA and
made in India by Sun Pharma and in 2013, FDA
approved the first generic version of Doxil,
made by Sun Pharma (Berger et al. 2014; Chou
et al. 2015).
In a study, it was observed that Doxil was also
active against refractory ovarian cancer, and
later approved by the FDA for the treatment of
recurrent ovarian cancer also (Muggia 1997;
Barenholz 2012). Recently, it has been approved
for the treatment of breast cancer (Barenholz
2012) in USA and for the treatment of multiple
myeloma in combination with velcade in Europe
and Canada (Blade et al. 2011; Barenholz 2012).
DaunoXome, the registered trademark of Galen,
is the liposomal formulation of daunorubicin
approved by the FDA for the treatment of AIDS
related kaposi’s sarcoma (Cooley et al. 2007;
Petre and Dittmer 2007). Myocet, the registered
trade mark of Cephalon, is a non-PEGylated
liposomal formulation of doxorubicin. Myocet
in combination with cyclophosphamide was
approved for the treatment of metastatic breast
cancer in Europe but was not yet approved by
the FDA for use in the United States (Batist et
al. 2001).
The Sopherion Therapeutics in the United States
and Canada is conducting a pivotal phase III
global registrational trial of Myocet in
combination with Herceptin (trastuzumab) and
Taxol (paclitaxel) for the treatment of highly
aggressive HER2-positive metastatic breast
cancer (Baselga et al. 2014). The liposomal
formulation of vincristine made by Talon was
registered under trade name of Marqibo.
Marqibo was approved in 2012 by the FDA for
the treatment of acute lymphoblastic leukemia
(Sarris et al. 2000; Rodriguez et al. 2009).
Celator Pharmaceuticals Inc developed CPX351, a liposomal formulation of cytarabine and
daunorubicin. The CPX-351 showed promising
results in phase III clinical trial on the patients
with secondary acute myeloid leukemia (AML)
by improving the induction response over 40%
(Riviere et al. 2011; Cortes et al. 2015).
Previously in phase II trial, CPX-351 had
already showed a survival benefits and the data
on over survival could be expected in the first
quarter of 2016 (Lancet et al. 2014). Another
liposomal formulation of Celator contains
irinotecan Hcl and floxuridine and registered as
CPX-1. The CPX-1 completed phase II clinical
trial on the patients with advanced colorectal
cancer (Batist et al. 2009). MM-398 is a
liposomal sphere encapsulating irinotecan
developed by Merrimack pharma. MM-398 is
being evaluated in the clinical trials for its
ability to treat various cancers, which are
resistant to chemotherapy such as pancreatic,
colorectal, lung and glioma (Ko et al. 2013; Roy
et al. 2013; Saif 2014). Another liposomal
formulation developed by Merrimack pharma is
MM-302, which encapsulates doxorubicin. MM302 is designed for selective uptake of drug into
tumor cells while sparing off healthy tissues.
MM-302 contains a novel antibody-drug
conjugated on the surface that specifically
targets cancer cells overexpressing the HER2
receptor. Currently, MM-302 is being evaluated
in phase I clinical trials for its ability to treat
advanced metastatic HER2-positive breast
cancer (Geretti et al. 2015). MBP-426 is
transferrin receptor targeted liposomal
formulation of oxaliplatin designed by
Mebiopharm. MBP-426 is being evaluated in
phase II clinical trial for the treatment of patients
with gastric cancer (Suzuki et al. 2008;
Goldberg et al. 2013).
Lipoplatin is the liposomal formulation of
cisplatin designed by Regulon Inc. and
currently, it is being evaluated in phase III
clinical trial for the patients with non-small cell
lung cancer (Fantini et al. 2011). Another
liposomal formulation Stimuvax is designed as
anti-MUC1 cancer vaccine by Oncothyreon to
treat non-small cell lung cancer and presently is
in phase III clinical trial (Bradbury and
Shepherd 2008; Fantini et al. 2011; Broglio et al.
2014). The thermo sensitive liposomal
formulation of doxorubicin, called ThermoDox
(Celsion) is under phase III clinical trial to treat
the patients with primary hepatocellular
carcinoma, in phase II for refractory chest wall
breast cancer and colorectal liver metastasis
(Poon and Borys 2011; Staruch et al. 2011).