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Liposomes, the vesicles of phospholipid bilayer, can encapsulate both hydrophilic and lipophilic drugs and protect them from degradation. Liposomes have been extensively studied and continue to create intense interest in research since their discovery in the mid-1960s. Since then, liposomes have been considered to be the most successful nanocarriers for drug deliver and have made their way to the market. Currently, a number of liposomal formulations are on the marker for cancer treatment and many more are in pipe line. This review discusses about the liposome components, methods of preparation, drug encapsulation mechanism and the potential therapeutic applications of liposomes in cancer therapy.
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Braz. Arch. Biol. Technol. v.59: e16150477, Jan/Dec 2016
Vol. 59: e16150477, January-December 2016
http://dx.doi.org/10.1590/1678-4324-2016150477
ISSN 1678-4324 Online Edition
BRAZILIAN ARCHIVES OF
BIOLOGY AND TECHNOLOGY
A N I N T E R N A T I O N A L J O U R N A L
Liposome and Their Applications in Cancer Therapy
Himanshu Pandey2, Radha Rani1, Vishnu Agarwal1*
1 Department of Biotechnology, Motilal Nehru National Institute of Technology (MNNIT), Allahabad, India 2
Faculty of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture Technology & Sciences, Allahabad,
India.
ABSTRACT
Liposomes, the vesicles of phospholipid bilayer, can encapsulate both hydrophilic and lipophilic drugs and protect
them from degradation. Liposomes have been extensively studied and continue to create intense interest in research
since their discovery in the mid-1960s. Since then, liposomes have been considered to be the most successful
nanocarriers for drug deliver and have made their way to the market. Currently, a number of liposomal
formulations are on the marker for cancer treatment and many more are in pipe line. This review discusses about
the liposome components, methods of preparation, drug encapsulation mechanism and the potential therapeutic
applications of liposomes in cancer therapy.
Keywords: Liposomes, Drug delivery, Cancer, Doxil, LipoDox, Myocet
*Author for correspondence: vishnua@mnnit.ac.in
Human & Animal Health
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INTRODUCTION
Cancer is the major health concern of the
century because of the leading cause of death
worldwide (Fitzmaurice et al. 2015; Torre et al.
2015). It kills millions of people very year and
its burden continues to rise at an alarming rate
globally (Stewart and Wild 2014). Cancer is the
uncontrolled growth of cells, which occurs due
to the accumulation of genetic mutations and
aberrant signaling of various pathways related to
the growth and survival of the cells (Bhardwaj et
al. 2014; Tyagi et al. 2014; Deshmukh et al.
2015; Srivastava et al. 2015a; Srivastava et al.
2015b). The complexity at genetic and
phenotypic levels in cancer cells leads to the
clinical diversity and therapeutic resistance in
cancer cells. Chemotherapy is most commonly
used treatment among a variety of approaches
currently being used for the treatment of cancer,
which, however, kpossesses several limitations
and side effects (MacDonald 2009; Ramirez et
al. 2009; Iwamoto 2013). According to an
estimate, more than 90% cancer drugs exhibit
poor bioavailability and pharmacokinetics
(Iwamoto 2013). Therefore, there is a
prerequisite to develop appropriate drug delivery
systems, which can improve the bioavailability,
pharmacokinetic properties and can deliver the
active drug molecules to the site of action,
without affecting the healthy cells.
To overcome the limitations of conventional
chemotherapy, a number of nanocarrier delivery
systems have been developed and extensively
used for drug delivery to cancer cells (Tyagi et
al. 2011; Tyagi et al. 2013; Arora et al. 2015).
Nanocarriers have larger surface area as
compared to bigger particles, which can be
easily modified to encapsulate large amount of
drug, to increase the blood circulation time and
to enhance the accumulation of drugs in solid
tumors via the enhanced permeability and
retention (EPR) effect as well as selective
targeting of tumor cells (Tyagi and Ghosh 2011;
Allen and Cullis 2013; Bozzuto and Molinari
2015).
Nanocarriers also improve the solubility,
bioavailability and pharmacokinetics properties
of chemotherapeutics (Gregoriadis and Florence
1993; Bozzuto and Molinari 2015; Pattni et al.
2015). Currently, a variety of nanocarriers such
as liposomes, polymeric nanoparticles, micelles,
nanotubes, etc are already in the market, or
under research and evaluation for cancer
treatment (Sutradhar and Lutful 2014). This
review summarizes the types of methods used
for the preparation of liposomes, mechanism of
drug loading and potential therapeutic
applications in cancer therapy and provides
current information on the liposomal products,
which are either in clinical use, or clinical trials.
LIPOSOMES
Bangham (Bangham et al. 1965) for the first
time observed that phospholipids in aqueous
medium forms closed bilayer structures. Later,
these closed bilayer structures were termed as
liposomes by Sessa (Sessa and Weissmann
1968). The liposome comprises of an aqueous
compartment surrounded by one, or more lipid
bilayers (Gregoriadis and Florence 1993; Pattni
et al. 2015).
Initially, liposomes were used to study the
physical behavior of biological membranes like
lipids orientation in bilayer, physiochemical
characterization of lipids and ion transport
across bio membranes (Bangham 1972;
Gregoriadis and Florence 1993). However, now
liposomes are extensively used for drug delivery
as they meet all the requirements of a good
delivery vehicle. Liposomes are biodegradable,
biocompatible, and stable in colloidal solutions
(Akbarzadeh et al. 2013; Allen and Cullis 2013).
Liposomes protect the drug from degradation
and reduce drug-related nonspecific toxicity and
can be produced and formulated easily for the
target specific delivery (Bitounis et al. 2012;
Bozzuto and Molinari 2015).
TYPES OF LIPOSOMES
Liposomes can be classified on the basis of size
and the number of phospholipid membrane
layers (Akbarzadeh et al. 2013; Pattni et al.
2015) as depicted in Figure 1.
Multilamellar Vesicles (MLV): These
liposomes are composed of a number of
concentric phospholipid bilayer membrane
separated by aqueous phase. These are big in
size and may be up to 5 μm.
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Small Unilamellar Vesicles (SUV): These
liposomes are composed of aqueous
compartment enclosed by a single lipid bilayer.
The size of these liposomes may be in the range
of 20-100 nm.
Large Unilamellar Vesicle (LUV): These
liposomes are also composed of a single lipid
bilayer surrounding aqueous compartment. The
size of these liposomes is in the range of 100-
250 nm.
Figure 1- Classification of liposomes based on the lamellarity: (A) Multilamellar Vesicles (MLV) is composed of
many lipid bilayers and ranges from 1-5 µm in size. (B) Large Unilamellar Vesicle (LUV) is in the size range of
100-250 nm with single lipid bilayer. (C) Small Unilamellar Vesicles (SUV) consists of a single phospholipid
bilayer surrounding the aqueous phase with size range 20-100 nm.
COMPONENTS OF LIPOSOMES
The major components of liposomes are
phospholipids and cholesterol, major
constituents of natural bio membranes. The
chemical properties of these lipids control the
behavior of liposomes.
Phospholipids
The most common phospholipids used for the
preparation of liposomes are natural (egg, or
soy) phosphatidylcholine, or synthetic
phosphatidylcholine (PC). The natural
phospholipids such as egg, or soyabean
phospholipids contain substantial levels of
polyunsaturated fatty acids making them less
stable than the synthetic equivalents (Jing Li et
al. 2015). The molar percentage of
phospholipids varies from 55 to 100% of total
liposomal components (Bozzuto and Molinari
2015; Jing Li et al. 2015). The most common
phospholipid component of liposomes is 2-
distearoyl-sn-glycerophosphocholine (DSPC).
The chemical structure of DSPC is presented in
Figure 2A. This molecule is composed of a polar
phosphate head group and the hydrophobic
portion composed of hydrocarbon chains. The
hydrocarbon chains form the interior and the
polar head forms the exterior of liposomes
bilayer. The head portion can be modified by
attaching a functional group. The 1,2-distearoyl-
sn-glycero-3-phosphoethanolamine (DSPE) is
an example of a functional phospholipid used to
conjugate other polymers like polyethylene
glycol (PEG) (Laouini et al. 2012; Marques-
Gallego and de Kroon 2014; Jing Li et al. 2015)
(Figure 2B). The type, molar percentage and
packing orientation of phospholipids determine
the ultimate shape and size of the liposomes
(Farge and Devaux 1992; Jing Li et al. 2015).
The orientation of phospholipids in liposome
bilayer depends upon the length of lipid
molecules and the size of head groups (Laouini
et al. 2012; Jing Li et al. 2015).
The phase transition temperature (Tc) of
phospholipids is also an important criterion to
choose phospholipid for the preparation of
liposomes (Laouini et al. 2012; Bozzuto and
Molinari 2015; Jing Li et al. 2015). The phase
transition temperature is defined as the
temperature at which the lipid physical state
converts from an ordered gel phase to a
disordered liquid crystalline phase. The
conversion of phases depends on hydrocarbon
chain length, degree of saturation, charge, and
head group species (Bitounis et al. 2012;
Laouini et al. 2012; Bozzuto and Molinari
2015).
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The use of phospholipids with higher phase
transition temperatures generates bilayers, which
are more stable (Ellens et al. 1986). This
decreases the possibility for premature leakage
of encapsulated components; however,
considerations must be made to ensure that
encapsulated drugs can still escape the
liposomes once they reach the target site of
action. On the other hand, if the phase transition
temperature of the selected phospholipids is too
high, denaturation of the encapsulated drugs
may occur during the sizing, or loading
processes (Bitounis et al. 2012; Laouini et al.
2012; Jing Li et al. 2015). Therefore, a good
balance must be met to guarantee that the
selected lipids have phase transition
temperatures that prevent premature leakage of
components but enable processing to occur at
temperatures that are harmless to all liposomal
components.
Figure 2- Chemical structures of common liposomal components: (A) 1, 2-distearoyl-sn-glycerophosphocholine
(DSPC) (B) Cholesterol and (C) 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol (DSPE-
PEG).
Cholesterol
The rotational freedom because of flip-flop
movements in phospholipids generates
liposomes of leaky properties. Cholesterol is the
main component added in the liposomal
formulations to stabilize the bilayer of liposomes
(Laouini et al. 2012; Magarkar et al. 2014).
Depending upon the rigidity and fluidity of
bilayer, the molar percentage of cholesterol
varies from 30-45% of total liposomes
components ( Kirby and Gregoriadis 1980;
Laouini et al. 2012) as it provides membrane
fluidity, elasticity, permeability and stability to
liposomes (Kirby and Gregoriadis 1980;
Magarkar et al. 2014). The chemical structure of
cholesterol is presented in Figure 2C.
The polar head of cholesterol is aligned with the
polar head of the phospholipids of lipid bilayer.
Due to hydrophobic properties of cholesterol, it
resides in the interior portion of lipid bilayers
and serves to fill the gap created because of
imperfect packing of phospholipid molecules.
The packing of cholesterol within phospholipid
bilayers prevents the flip-flop of membrane
components and the movement across the
membranes (Kirby and Gregoriadis 1980; Farge
and Devaux 1992).
Cholesterol also provides the rigidity to
liposomes as it prevents the phase transition of
lipid bilayers, and thus reduces the leakage of
encapsulated drugs (Manes and Martinez 2004).
Therefore, the percentage of cholesterol used for
the preparation of liposomes also affects the
ultimate phase transition temperature of the
bilayer. Some studies have suggested that the
cholesterol also helps in protecting the lipid
bilayer from hydrolytic degradation (Simon et
al. 1982). Depending on the final application of
liposomes, many other components in addition
to phospholipid and cholesterol have been used.
Depending upon the component used, liposomes
can be neutral, negative, or positively charged.
The charge on the surface of liposomes plays an
important role in deciding the fate and
application of the liposomes (Miller et al. 1998;
Tyagi et al. 2011). PEG is the other commonly
used liposome component typically incorporated
to increase the blood circulation times because
of its stealth properties and has shown broad
applications (Miller et al. 1998; Immordino et al.
2006; Tyagi and Ghosh 2011; Tyagi et al. 2013).
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METHODS OF PREPARATION
There are several methods for the preparation of
liposomes such as solvent removal, detergent
removal, emulsion removal and ethanol injection
(Laouini et al. 2012; Bozzuto and Molinari
2015). The type of preparation methods
influences the properties of liposomes, including
their shape, size, stability and drug loading
efficiency. Thin lipid film hydration, or solvent
removal method is the most common and first
described method for liposome preparations
(Akbarzadeh et al. 2013; Bozzuto and Molinari
2015). Briefly, the lipids are dissolved in
chloroform and/or methanol mixture. The
concentration of lipids is typically in the range
of 10-20 mgmL-1 depending on the solubility of
lipids.
The solvent is subsequently removed by a rotary
evaporator under reduced pressure to produce a
thin film of lipids. The thin film so formed is
desiccated for required time, followed by
hydration. Hydration of the dry lipid film is
accomplished by adding aqueous solution,
which has the osmolarity in physiological range.
After completion of hydration, the liposomes of
multilamellar vesicles (LMV) in the size range
of 200-1000 nm are produced (Laouini et al.
2012; Akbarzadeh et al. 2013). These MLVs are
broken down into smaller liposomes by
sonication, or extrusion.
Sonication is generally performed in water bath
type sonicators and the temperature of water is
maintained above the Tc of lipids. Sonic waves
disrupt the outer layers of gaint liposomes and
produce small unilamellar vesicles (SUV),
ranging between 20-100 nm in diameter
(Laouini et al. 2012; Akbarzadeh et al. 2013).
The final size of liposomes not only depends
upon the sonication time and energy but also
upon many factors, including lipid composition,
concentration and suspension volume.
Alternatively, the liposomes are passed through
the extrusion assembly containing a
polycarbonate membrane of definite size to
reduce the size of MLVs. This process is also
performed under high pressure and at a
temperature above the lipid Tc. The final size of
extruded liposomes tends to be close to the filter
pore size. Extrusion through filters with 100 nm
pores yields large unilamellar vesicles (LUV) of
reproducible size.
ENCAPSULATION OF DRUGS INTO
LIPOSOMES
The methods of drug encapsulation in to the
liposomes can be divided into two sub groups.
The passive loading in which drug encapsulation
occur during the vesicle formation process and
the active loading in which drug is entrapped
after the formation of vesicles.
Passive loading
Passive loading is to encapsulate the drug during
the formation of liposomes. The hydrophilic
drugs are loaded within the internal core of the
liposomes by mixing with the hydrating buffer
used to hydrate the thin lipid film during the
formation of liposomes. Lipophilic drugs are
mixed with other liposome components during
the preparation of thin dry film of lipids and
ultimately loaded into lipid bilayers. The un-
entrapped drug molecules are removed from
liposome suspension by dialysis, or gel-filtration
chromatography (Tyagi et al. 2011; Tyagi et al.
2013).
The encapsulation efficiency depends on lipid
concentration, liposome size, choice of lipids,
etc. The encapsulation efficiency of water-
soluble compounds, which do not interact with
the lipid bilayer, is relatively low if loaded by
passive method and proportional to the aqueous
volume enclosed in the liposomes (Tyagi et al.
2013). Large vesicles will have higher
encapsulation efficiency than small vesicles
(Akbarzadeh et al. 2013). While the drug that
interacts with lipid bilayer, such as lipophilic
compound, normally have better encapsulation
rate.
Therefore, several strategies have been
developed to improve the encapsulation
efficiency by linking lipophilic chain to drug
molecule to increase its lipophilicity and better
partition into the lipid bilayer (Sutradhar and
Lutful 2014; Bozzuto and Molinari 2015).
Choice of lipid composition is also critical for
better loading efficiently by this method. For
example, to load highly negatively charged
nucleotide compounds, such as antisense or
siRNA, selection of cationic lipid will greatly
improve the encapsulation efficiency due to
enhanced drug/lipid interaction.
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Active loading
Certain weakly acidic, or alkaline drug
molecules are loaded into preformed liposomes
by active loading, or remote loading method.
This process is driven by an electrochemical
potential created by the pH, or ion gradients
established across the lipid bilayer of the
liposomes (Akbarzadeh et al. 2013; Bozzuto and
Molinari 2015). The pH, or ion gradients are
created during the liposomes preparation by
using a buffer of specified pH and ion
concentration. The external pH of liposomes is
then exchanged with another buffer of different
pH, or ion concentration through dialysis, or size
exclusion chromatography. After creating the
pH gradient across the liposomes membranes,
drug is loaded by mixing with liposomes
typically at a temperature above the phase
transition temperature of the lipids to ensure the
fluidity and efficient transport across the bilayer.
The drug molecules interact with the ions within
liposomes and get charged. The charged drug
molecules are not capable to come out and
remain entrapped within liposome core.
Doxil™, liposomal doxorubicin, is the ideal
example of the active loading by pH gradient
method (Lasic et al. 1992; Haran et al. 1993).
The active loading of doxorubicin by pH
gradient method is shown in Figure 3. As shown
in the figure, when the gradient of citrate buffer
liposome is more than 1000 times to the citrate
buffer of medium then a pH gradient is created.
Doxorubicin, a weak base, is in equilibrium
between an ionized state and a non-ionized state.
The latter can cross the lipid bilayer, become
ionized in the high proton intraliposome
environment and leads to high efficient
accumulation of doxorubicin inside the
liposome. The another example of pH-gradient
method is the loading of chloroquine
diphosphate into liposomes (Qiu et al. 2008). In
another study, oxymatrine- major active alkaloid
constituent extracted from the traditional
Chinese herb medicine Sophora flavescens, used
for treating hepatitis B in clinical therapy in
China, was also loaded into liposomes by pH
gradient method (Du and Deng 2006).
Figure 3- Active loading of drugs into liposomes: Liposomes were prepared by hydrating in citrate buffer ( ) and
then external phase was exchanged with Na2CO3 ( ) to create a pH gradient. (C) The neutral form of the externally
added drug ( ) can cross the bilayer and is protonated ( ) and trapped inside the vesicles.
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
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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 CPX-
351, 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. MM-
302 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).
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CONCLUSION
Liposomes have revolutionized cancer
therapy by their broad clinical applications.
Liposomes overcome the limitations of
conventional chemotherapy by improving the
bioavailability and stability of the drug
molecules and minimizing side effects by site-
specific targeted delivery of the drugs.
Liposomes were the first nanotechnology-based
drug delivery systems approved for the clinical
applications because of their biocompatibility
and biodegradability like features. Some
liposome-based drug delivery systems are
already in the market and many more are
undergoing research and clinical trials. So far,
liposomes have established themselves in
nanocarriers-based drug delivery systems as
evident by the successful clinical applications of
liposomal formulations in anti-cancer therapy.
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Received: 24-Aug - 2015
Accepted: 08-Oct-2015
... This change in the structure of liposomes increases their cellular uptake activity. The effects of ionizable liposomes in the therapy of various diseases are still poorly understood, but there is a growing body of experimental data suggesting that their use provides significant advantages over other types of therapeutic methods [21][22][23]. ...
... One is the passive targeting through the well-known enhanced permeability and retention (EPR) effect [13,14], and the other is the active targeting which uses certain functional groups to combine with the receptor on the tumor sites, so-called receptor-mediated endocytosis [13,15,16]. In recent years, a lot of SDDSs materials have been well-developed, like liposome [17], dendrimer [18], and polymer micelle [19]. ...
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... 74 Liposomes, due to their biocompatible, biodegradable, and stable characteristics in colloidal solutions, are a viable option for targeted drug delivery, particularly in the context of cancer therapy. According to Exelead 74 and Pandey et al., 75 liposomes serve the purpose of safeguarding drugs from enzymatic degradation and diminishing drug-associated non-specific toxicity. ❖ Encapsulation of drugs within liposomes provides protection against detection by the host's immune system, as the liposome structure mimics biological membranes, allowing for sufficient time for the drug to reach its intended target. ...
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