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Liposomal drug delivery system - A Comprehensive Review


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The role of bilayerd vesicles as efficient carriers for drugs, vaccines, diagnostic agents and other bioactive agents have led to a rapid advancement in the liposomal drug delivery system. Moreover, the siteavoidance and site-specific drug targeting therapy could be achieved by formulating a liposomal product, so as to reduce the cytotoxicity of many potent therapeutic agents. This article is intended to provide an overview of liposomal drug delivery system. It has focused on the factors affecting the behavior of the liposomes in the biological environment. Various aspects related to mechanism of liposome formation, characterization and stability of the liposomal drug product were also discussed in the article. Liposomes can be used as a therapeutic tool in the fields like tumor targeting, genetic transfer, immunomodulation, skin and topical therapy.
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Advances in combinatorial chemistry have led to
the discovery of a wide number of new chemical
entities (NCE) that have a potential therapeutic
action on the biological systems. But most of the
NCEs being discovered provide a challenge to
the formulation scientist because of their physico-
chemical properties like poor solubility and
permeability. Even though, above problems could
be addressed, but most of the molecules fail to
show their desired therapeutic action in vivo,
which leads to lack of in vitro – in vivo correlation
A majority of anti-neoplastic agents, which are
highly cytotoxic to tumor cells in vitro, affect the
normal cells also. This is due to their low
therapeutic index (TI), i.e., the dose required to
produce anti-tumor effect is toxic to normal cells.
Such drugs have to be targeted to a specific site
(diseased site) in order to reduce their toxic
effects to normal tissues
. Hence, an efficient
drug delivery system is required to present the
maximum fraction of administered dose at the
target site. Various carriers like nanoparticles,
microparticles, polysaccharides, lectins and
liposomes can be used to target the drug to a
specific site
Liposomal drug delivery is gaining interest due to
its contribution to varied areas like drug delivery,
cosmetics, and structure of biological membrane
. Liposomes can act as a carrier for a variety of
drugs, having a potential therapeutic action.
Liposomes are colloidal carriers, having a size
range of 0.01 5.0 µm in diameter. Indeed these
are bilayered vesicles that are formed when
Copyright © 2013 By IYPF
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Open Access Contents
Int. J. Drug Dev. & Res.
| October - December 2013 | Vol. 5 | Issue 4 | ISSN 0975-9344 |
Liposomal drug delivery system - A Comprehensive Review
Department of Pharmaceutical
Technology, Shri Vishnu College of
Pharmacy, Bhimavaram, Andhra
Pradesh, India.
Corresponding Authors:
Kalepu Sandeep,
Dept. of Pharmaceutical
Technology, Shri Vishnu College of
Pharmacy, Bhimavaram-534202,
Dist: West Godavari,
Andhra Pradesh, INDIA.
The role of bilayerd vesi
cles as efficient carriers for drugs, vaccines,
diagnostic agents and other bioactive agents have led to a rapid
advancement in the liposomal drug delivery system. Moreover, the site
avoidance and site-
specific drug targeting therapy could be achieved
by f
ormulating a liposomal product, so as to reduce the cytotoxicity of
many potent therapeutic agents. This article is intended to provide an
overview of liposomal drug delivery system. It has focused on the factors
affecting the behavior of the liposomes in
Various aspects related to mechanism of liposome formation,
characterization and stability of the liposomal drug product were also
discussed in the article. Liposomes can be used as a therapeutic tool in
the fields like tumor t
argeting, genetic transfer, immunomodulation, skin
and topical therapy.
Liposomal formulation, bilayered vesicles, percent drug
encapsulation, cytotoxic.
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isher and licensee IYPF. This is an Open Access article which permits unrestricted
noncommercial use, provided the original work is properly cited.
phospholipids are hydrated in excess of aqueous
. Liposomes have got a potential
advantage of encapsulating hydrophilic as well
as hydrophobic drugs and targeting them to the
required diseased site in the body
. Fig. 1
depicts the structure of a liposome (bilayered
vesicle) and phospholipid.
Fig. 1: Structure of liposome and phospholipid
Various therapeutic agents like anticancer drugs,
vaccines, antimicrobials, genetic materials,
proteins and macromolecules can be
encapsulated within the bilayered vesicles
Liposomal technology was used for the successful
encapsulation of various drug molecules like
, acyclovir
, tropicamaide
, chloroquine diphosphate
and dithranol
. Table 1
indicates the list of few liposomal products that
have been approved for human use
Table 1: List of liposomal products approved for commercial use
Drug Product Indication
Ambisome™ Amphoteracin B Fungal infection
Daunorubicin Kaposi's sarcoma
Doxil™ Doxorubicin Refractory Kaposi's sarcoma, recurrent breast cancer and ovarian cancer
Visudyne® Verteporfin Age-related macular degeneration, pathologic myopia and ocular
Myocet® Doxorubicin Recurrent breast cancer
DepoCyt® Cytarabine Neoplastic meningitis and lymphomatous meningitis
Lipoplatin® Cisplatin Epithelial malignancies
DepoDur® Morphine
sulfate Postoperative pain following major surgery
The basic part of liposome is formed by
phospholipids, which are amphiphilic molecules
(having a hydrophilic head and hydrophobic
tail). The hydrophilic part is mainly phosphoric
acid bound to a water soluble molecule,
whereas, the hydrophobic part consists of two
fatty acid chains with 10 24 carbon atoms and
0 – 6 double bonds in each chain
When these phospholipids are dispersed in
aqueous medium, they form lamellar sheets by
organizing in such a way that, the polar head
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Page 63
group faces outwards to the aqueous region
while the fatty acid groups face each other and
finally form spherical/ vesicle like structures called
as liposomes. The polar portion remains in
contact with aqueous region along with shielding
of the non-polar part (which is oriented at an
angle to the membrane surface)
When phospholipids are hydrated in water, along
with the input of energy like sonication, shaking,
heating, homogenization, etc. it is the
hydrophilic/ hydrophobic interactions between
lipid – lipid, lipid – water molecules that lead to
the formation of bilayered vesicles in order to
achieve a thermodynamic equilibrium in the
aqueous phase
. The reasons for bilayered
formation include:
The unfavorable interactions created
between hydrophilic and hydrophobic
phase can be minimized by folding into
closed concentric vesicles.
Large bilayered vesicle formation promotes
the reduction of large free energy
difference present between the hydrophilic
and hydrophobic environment.
Maximum stability to supramolecular self
assembled structure can be attained by
forming into vesicles.
Various classes of liposomes have been reported
in literature. They are classified based on their
size, number of bilayers, composition and method
of preparation. Based on the size and number of
bilayers, liposomes are classified as multilamellar
vesicles (MLV), large unilamellar vesicles (LUV)
and small unilamellar vesicles (SUV) as depicted
in Fig. 2. Based on composition, they are classified
as conventional liposomes (CL), pH-sensitive
liposomes, cationic liposomes, long circulating
liposomes (LCL) and immuno-liposomes. Based
on the method of preparation, they are classified
as reverse phase evaporation vesicles (REV),
French press vesicles (FPV) and ether injection
vesicles (EIV). In this context, the classification
based on size and number of bilayers is discusse
Fig. 2: Classification of liposomes based on size and number of bilayers
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Multilamellar vesicles (MLV)
MLV have a size greater than 0.1 µm and consist
of two or more bilayers. Their method of
preparation is simple, which includes thin – film
hydration method or hydration of lipids in excess
of organic solvent. They are mechanically stable
on long storage. Due to the large size, they are
cleared rapidly by the reticulo-endithelial system
(RES) cells and hence can be useful for targeting
the organs of RES
. MLV have a moderate
trapped volume, i.e., amount of aqueous volume
to lipid ratio. The drug entrapment into the
vesicles can be enhanced by slower rate of
hydration and gentle mixing
. Hydrating thin
films of dry lipids can also enhance encapsulation
. Subsequent lyophilization and
rehydration after mixing with the aqueous phase
(containing the drug) can yield MLV with 40%
encapsulation efficiency
Large unilamellar vesicles (LUV)
This class of liposomes consists of a single bilayer
and has a size greater than 0.1 µm. They have
higher encapsulation efficiency, since they can
hold a large volume of solution in their cavity
They have high trapped volume and can be
useful for encapsulating hydrophilic drugs.
Advantage of LUV is that less amount of lipid is
required for encapsulating large quantity of drug.
Similar to MLV, they are rapidly cleared by RES
cells, due to their larger size
. LUV can be
prepared by various methods like ether injection,
detergent dialysis and reverse phase evaporation
techniques. Apart from these methods, freeze-
thawing of liposomes
, dehydration/
rehydration of SUV
and slow swelling of lipids in
non-electrolyte solution
can also be used to
prepare LUV.
Small unilamellar vesicles (SUV)
SUV are smaller in size (less than 0.1 µm) when
compared to MLV and LUV, and have a single
bilayer. They have a low entrapped aqueous
volume to lipid ratio and characterized by having
long circulation half life. SUV can be prepared by
using solvent injection method (ethanol or ether
injection methods)
or alternatively by reducing
the size of MLV or LUV using sonication or
extrusion process under an inert atmosphere like
nitrogen or Argon. The sonication can be
performed using either a bath or probe type
sonicator. SUV can also be achieved by passing
MLV through a narrow orifice under high pressure.
These SUV are susceptible to aggregation and
fusion at lower or negligible/ no charge
The conventional methods for preparing
liposomes include solubilizing the lipids in organic
solvent, drying down the lipids from organic
solution, dispersion of lipids in aqueous media,
purification of resultant liposomes and analysis of
the final product
Of all the methods used for preparing liposomes,
thin-film hydration method is the most simple and
widely used one. MLV are produced by this
method within a size range of 1 – 5 µm. If the drug
is hydrophilic it is included in the aqueous buffer
and if the drug is hydrophobic, it can be included
in the lipid film. But the drawback of this method
is poor encapsulation efficiency (5 – 15% only) for
hydrophobic drugs. By hydrating the lipids in
presence of organic solvent, the encapsulation
efficiency of the MLV can be increased
can be prepared by solvent injection, detergent
dialysis, calcium induced fusion and revese
phase evaporation techniques. SUV can be
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Page 65
prepared by the extrusion or sonication of MLV or
All these preparation methods involve the usage
of organic solvents or detergents whose
presence even in minute quantities can lead to
toxicity. In order to avoid this, other methods like
polyol dilution
, bubble method
and heating
have been developed without using
any organic solvents or detergents. Detailed
procedures for liposome preparation, can be
obtained from literature
Liposomes produced by different methods have
varying physicochemical characteristics, which
leads to differences in their in vitro (sterilization
and shelf life) and in vivo (disposition)
. Rapid, precise and
reproducible quality control tests are required for
characterizing the liposomes after their
formulation and upon storage for a predictable
in vitro and in vivo behavior of the liposomal drug
. A liposomal drug product can be
characterized for some of the parameters that
are discussed below.
Size and size distribution
When liposomes are intended for inhalation or
parenteral administration, the size distribution is of
primary consideration, since it influences the in
vivo fate of liposomes along with the
encapsulated drug molecules
. Various
techniques of determing the size of the vesicles
include microscopy (optical microscopy
negative stain transmission electron microscopy
, cryo-transmission electron microscopy
freeze fracture electron microscopy and
scanning electron microscopy
), diffraction
and scattering techniques (laser light scattering
and photon correlation spectroscopy)
hydrodynamic techniques (field flow
, gel permeation
Percent drug encapsulation
The amount of drug encapsulated/ entrapped in
liposome vesicle is given by percent drug
encapsulation. Column chromatography can be
used to estimate the percent drug encapsulation
of liposomes
. The formulation consists of both
free (unencapsulated) and encapsulated drug.
So as to know the exact amount of drug
encapsulated, the free drug is separated from
the encapsulated one. Then the fraction of
liposomes containing the encapsulated drug is
treated with a detergent, so as to attain lysis,
which leads to the discharge of the drug from the
vesicles into the surrounding medium. This
exposed drug is assayed by a suitable technique
which gives the percent drug encapsulated from
which encapsulation efficiency can be
Trapped volume per lipid weight can also give
the percent drug encapsulated in a liposome
vesicle. It is generally expressed as aqueous
volume entrapped per unit quantity of lipid,
µl/µmol or µg/mg of total lipid
. Inorder to
determine the trapped volume, various materials
like radioactive markers, fluorescent markers and
spectroscopically inert fluid
can be used.
Radioactive method is mostly used for
determining trapped volume
. It is determined
by dispersing lipid in an aqueous medium
containing a non-permeable radioactive solute
like [
Na] or [
C] inulin
. Alternatively, water
soluble markers like 6-carboxyfluorescein,
C or
H-glucose or sucrose can be used to determine
the trapped volume
. A novel method of
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determining intravesicular volume by salt
entrapment was also reported in literature
Surface charge
Since the charge on the liposome surface plays a
key role in the in vivo disposition, it is essential to
know the surface charge on the vesicle surface.
Two methods namely, free-flow electrophoresis
and zeta potential measurement can be used to
estimate the surface charge of the vesicle. The
surface charge can be calculated by estimating
the mobility of the liposomal dispersion in a
suitable buffer (determined using Helmholtz–
Smolochowski equation)
Vesicle shape and lamellarity
Various electron microscopic techniques can be
used to assess the shape of the vesicles. The
number of bilayers present in the liposome, i.e.,
lamellarity can be determined using freeze-
fracture electron microscopy
magnetic resonance analysis
. Apart from
knowing the shape and lamellarity, the surface
morphology of liposomes can be assessed using
freeze-fracture and freeze-etch electron
Phospholipid identification and assay
The chemical components of liposomes must be
analyzed prior to and after the preparation
Barlett assay
, Stewart assay
and thin layer
can be used to estimate the
phospholipid concentration in the liposomal
formulation. A spectrophotometric method to
quantify total phosphorous in a sample was given
in literature, which measure the intensity of blue
color developed at 825 nm against water
Cholesterol oxidase assay or ferric perchlorate
and Gas liquid chromatography
techniques can be used to determine the
cholesterol concentration
During the development of liposomal drug
products, the stability of the developed
formulation is of major consideration. The
therapeutic activity of the drug is governed by
the stability of the liposomes right from the
manufacturing steps to storage to delivery. A
stable dosage forms is the one which maintains
the physical stability and chemical integrity of the
active molecule during its developmental
procedure and storage. A well designed stability
study includes the evaluation of its physical,
chemical and microbial parameters along with
the assurance of product’s integrity throughout its
storage period. Hence a stability protocol is
essential to study the physical and chemical
integrity of the drug product in its storage.
Physical stability
Liposomes are bilayered vesicles that are formed
when phospholipids are hydrated in water. The
vesicles obtained during this process are of
different sizes. During its storage, the vesicles tend
to aggregate and increase in size to attain
thermodynamically favorable state. During
storage, drug leakage from the vesicles can
occur due to fusion and breaking of vesicles,
which deteriorates the physical stability of the
liposomal drug product. Hence morphology, size
and size distribution of the vesicles are important
parameters to assess the physical stability
. In
order to monitor this, a variety of techniques like
light scattering and electron microscopy
be used to estimate the visual appearance
(morphology) and size of the vesicles.
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Page 67
Chemical stability
Phospholipids are chemically unsaturated fatty
acids that are prone to oxidation and hydrolysis,
which may alter the stability of the drug product.
Along with this, pH, ionic strength, solvent system
and buffered species also play a major role in
maintaining a liposomal formulation. Indeed
chemical reaction can be induced even by light,
oxygen, temperature and heavy metal ions.
Oxidation deterioration involves the formation of
cyclic peroxides and hydroxyperoxidases due to
the result of free radical generation in the
oxidation process. Liposomes can be prevented
from oxidative degradation by protecting them
from light, by adding anti-oxidants such as alpha
tocopherol or butylated hydroxyl toluene (BHT),
producing the product in an inert environment
(presence of nitrogen or Argon) or by adding
EDTA to remove trace heavy metals
Hydrolysis of the ester bond at carbon position of
the glycerol moiety of phospholipids leads to the
formation of lyso-phosphatidylcholine (lysoPC),
which enhances the permeability of the
liposomal contents. Hence, it becomes necessary
to control the limit of lysoPC within the liposomal
drug product. This can be achieved by
formulating liposomes with phosphatidylcholine
free from lysoPC
During the optimization of liposomal formulation,
various physico-chemical parameters are altered
in order to achieve a desired bio-distribution and
cellular uptake of drugs. Those parameters which
affect the in vivo (biological) performance of
liposomes are described below
Liposome size
The size of the vesicle governs the in vivo fate of
liposomes, because it determines the fraction
cleared by RES
. The rate of uptake of liposome
by RES increases with the vesicle size. Liposomes
larger than 0.1 µm are taken up (opsonized) more
rapidly by RES, when compared to liposomes
smaller than 0.1 µm.
The size of the vesicle also determines the
extravasation of liposomes. Tumor capillaries are
more permeable than normal capillaries. Due to
such leaky vasculature, fluids along with small
sized liposomes can pass through the gaps
leading to increased accumulation of drug
loaded liposomes in the tumor tissue. The
difference between intravascular hydrostatic and
interstitial pressure acts as a driving force for the
extrvasation of small sized liposomes
Surface charge
The lipid – cell interaction can be governed by
the nature and density of charge on the
liposome surface. Charging the lipid composition
can alter the nature and charge on the
liposome. Lack of charge in the SUV liposomes
can lead to their aggregation and thereby
reducing the stability of the liposome; whereas,
the interaction of neutrally charged liposome
with the cell is almost negligible
. High
electrostatic surface charge on the liposome
may provide useful results in promoting lipid – cell
interaction. Negatively charged density
influences the extent of lipid – cell interactions
and increase the intracellular uptake of
liposomes by target cells
. But positively
charged liposomes are cleared more rapidly
after systemic administration. Unlike negatively
charged liposomes, cationic liposomes deliver
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his is an Open Access article which permits unrestricted
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the contents to cells by fusion with cell
Surface hydration
Liposomes with hydrophilic surface coatings are
less prone to opsonization, hence reducing its
uptake by RES cells. This can be attributed to the
hydrophilic surface coating, which reduces the
interaction of liposomes with cell and blood
. These sterically stabilized
liposomes are more stable in the biological
environment and exhibit high circulation half
lives, when compared to liposomes coated with
hydrophobic coatings. Monogangliosides,
hydrogenated phosphotidyl inositol, polyethylene
glycol are some of the hydrophilic groups
responsible for steric stabilization of liposomes
Bilayer fluidity
Lipid exists in different physical states above and
below the phase transition temperature (Tc). They
are rigid and well ordered below Tc but are in
fluid like liquid – crystalline state above Tc. Table 2
inidcates the phase transition temperatures of
various phospholipids
. Liposomes with low Tc
(less than 37°C) are fluid like and are prone to
leakage of the drug content at physiological
temperature. But, the liposomes with high Tc
(greater than 37°C) are rigid and less leaky at
physiological temperature.
The phase transition temperature also governs
the liposomal cell interaction. Liposomes with low
Tc lipids have high extent of uptake by RES when
compared to those with high Tc lipids
Incorporation of cholesterol in the bilayer can
decrease the membrane fluidity at a
temperature greater than phase transition
temperature, which gives stability to liposomes.
Table 2: Phase transition temperatures of various
Name of the phospholipid Molecular
677.94 23
Dioleoyl PC (DOPC) 786.12 -22
Distearoyl PC (DSPC) 790.15 55
691.97 67
Dipalmitoyl PC (DPPC) 734.05 41
744.96 41
When a conventional dosage form fails to
provide a desired therapeutic effect, then new
drug delivery systems are developed. Liposomes
are among such systems which provide a superior
therapeutic efficacy and safety in comparison to
existing formulations. Some of the major
therapeutic applications of liposomes in drug
delivery include:
Site-avoidance delivery
The cytotoxicity of anti-cancer drugs to normal
tissues can be attributed to their narrow
therapeutic index (TI). Under such circumstances,
the TI can be improved by minimizing the delivery
of drug to normal cells by encapsulating in
liposomes. Free doxorubicin has a severe side
effect of cardiac toxicity, but when formulated as
liposomes, the toxicity was reduced without any
change in the therapeutic activity
Site specific targeting
Delivery of larger fraction of drug to the desired
(diseased) site, by reducing the drug’s exposure
to normal tissues can be achieved by site specific
targeting. Encapsulating the drug in liposomes
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Page 69
can be used for both active and passive
targeting of drugs in order to achieve a safer and
efficacious therapy
. On systemic
administration, long circulating immunoliposomes
are able to recognize and bind to target cells
with greater specificity
. In patients with
recurrent osteosarcoma, there was an enhanced
tumoricidal activity of monocytes, when muramyl
peptide derivatives were formulated as liposomes
and administered systemically
Intracellular drug delivery
Increased delivery of potent drugs to the cytosol
(in which drug’s receptors are present), can be
accomplished using liposomal drug delivery
. N-(phosphonacetyl)-L-aspartate (PALA)
is normally poorly taken up into cells. Such drugs
when encapsulated within liposomes, showed
greater activity against ovarian tumor cell lines in
comparison to free drug
Sustained release drug delivery
Liposomes can be used to provide a sustained
release of drugs, which require a prolonged
plasma concentration at therapeutic levels to
achieve the optimum therapeutic efficacy
Drugs like cytosine Arabinoside can be
encapsulated in liposomes for sustained release
and optimized drug release rate in vivo
IntraperitoneaI administration
Tumors that develop in the intra-peritoneal (i.p.)
cavity can be treated by administering the drug
to i.p. cavity. But the rapid clearance of the
drugs from the i.p. cavity results in minimized
concentration of drug at the diseased site.
However, liposomal encapsulated drugs have
lower clearance rate, when compared to free
drug and can provide maximum fraction of drug
in a prolonged manner to the target site
Immunological adjuvants in vaccines
Immune response can be enhanced by
delivering antigens encapsulated within
liposomes. Depending on the lipophilicity of
antigens, the liposome can accommodate
antigens in the aqueous cavity or incorporate
within the bilayers
. In order to enhance the
immune response to diphtheria toxoid, liposomes
were first used as immunological adjuvants
A number of drug candidates which are highly
potent and have low therapeutic indication can
be targeted to the required diseased site using
the liposomal drug delivery system. Drugs
encapsulated in liposomes can have a
significantly altered pharmacokinetics. The
efficacy of the liposomal formulation depends on
its ability to deliver the drug molecule to the
targeted site over a prolonged period of time,
simultaneously reducing its (drug’s) toxic effects.
The drugs are encapsulated within the
phospholipid bilayers and are expected to diffuse
out from the bilayer slowly. Various factors like
drug concentration, drug to lipid ratio,
encapsulation efficiency and in vivo drug release
must be considered during the formulation of
liposomal drug delivery systems. The
development of deformable liposomes and
ethosomes along with the administration of drug
loaded liposomes through inhalation and ocular
route are some of the advances in the
technology. Thus liposomal approach can be
successfully utilized to improve the
pharmacokinetics and therapeutic efficacy,
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Article History: ------------------------
Date of Submission: 29-08-2013
Date of Acceptance: 17-09-2013
Conflict of Interest: NIL
Source of Support: NONE
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... Structure of liposome and lipid bilayer. [9] Ganesh Shankar Sawant Liposome are also defined as artificial microscopic vesicles consisting of aqueous compartment and surrounded by one or more concentric layer of phospholipid. The sphere like encapsulated a liquid interior contain more substance like peptides, protein, hormones, enzymes, antibiotic, antifungal and anticancer agents. ...
... Table indicates phase transition temperature of various phospholipids. [9,10,11] History of liposome- ...
... Classification of liposome based on size and number of bilayer.[9] ...
Liposome is a spherical sac phospholipid molecule. It encloses a water droplet especially as form artificially to carry drug into tissue membrane. It is spherical sac vesicle it consists at least one lipid bilayer. Liposomes are mainly development for drug delivery size and size distribution. The process of sonication (extrusion) is required to obtain small size and narrow size distribution of liposome. The main significant role in formulating of potent drug, improve therapeutic effect. Liposome formulation is mainly design in increasing accumulation at the target site, and then resulting effect is targeted to reduce toxicity. There is various method for liposome formulation depending upon lipid drug interaction liposome disposition mechanism- parameters particle size, charge and surface hydration. Liposome is a nanoparticle (size-100nm). Nanoscale drug delivery system using liposome as well as nanoparticle. This technology is for "Rational delivery of chemotherapeutic" drug treatment of cancer. Liposome is use as to study the cell membrane and cell organelles. The advantages of liposome formation using microfluidic approach for bulk-mixing approaches are discussed. Keywords: liposome, lipid bilayer, sonication, nanoparticles, particle size, toxicity.
... Liposomes are bilayer vesicles with 0.01-5.0 μm size that are shaped when phospholipids are hydrated in an aqueous medium, providing them the capability to deliver both hydrophilic and hydrophobic drugs (Kalepu, Sunilkumar, & Betha, 2013). Besides their ability to deliver hydrophilic and lipophilic drugs, liposomes are biocompatible vesicles with self-assembly capacity and modifiable biophysical and physicochemical properties (Guimarães, Cavaco-Paulo, & Nogueira, 2021). ...
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Silymarin, a milk thistle extract, has anti-inflammatory, immunomodulatory, anti-lipid peroxidative, anti-fibrotic, anti-oxidative, and anti-proliferative properties. Silymarin exhibits not only anti-cancer functions through modulating various hallmarks of cancer, including cell cycle, metastasis, angiogenesis, apoptosis, and autophagy, by targeting a plethora of molecules, but also plays protective roles against chemotherapy-induced toxicity, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, and neurotoxicity. One of the problems of silymarin in (pre)clinical studies is its poor water solubility, leading to low intestinal absorption and, therefore, low bioavailability. To address these challenges, silymarin nanoformulations have emerged with added benefits, including excellent drug loading, sustained release, improved cellular uptake, and targeting tumor cells. Besides the chemical and biological properties, here we summarized the anti-cancer functions and the mechanism of action of silymarin in both free form and nanoformulations and its protective roles against chemotherapy-induced toxicity.
... The "melting" of a bilayer refers to the solid (gel) to liquid transition, and not the melting of the lipid components themselves. This also depends on the lipid composition; longer chain lipids typically have a higher phase transition temperature [239,240]. ...
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The origin of life on Earth required myriads of chemical and physical processes. These include the formation of the planet and its geological structures, the formation of the first primitive chemicals, reaction, and assembly of these primitive chemicals to form more complex or functional products and assemblies, and finally the formation of the first cells (or protocells) on early Earth, which eventually evolved into modern cells. Each of these processes presumably occurred within specific prebiotic reaction environments, which could have been diverse in physical and chemical properties. While there are resources that describe prebiotically plausible environments or nutrient availability, here, we attempt to aggregate the literature for the various physicochemical properties of different prebiotic reaction microenvironments on early Earth. We introduce a handful of properties that can be quantified through physical or chemical techniques. The values for these physicochemical properties, if they are known, are then presented for each reaction environment, giving the reader a sense of the environmental variability of such properties. Such a resource may be useful for prebiotic chemists to understand the range of conditions in each reaction environment, or to select the medium most applicable for their targeted reaction of interest for exploratory studies.
... The computerized combinatorial chemistry has led to discovering new drug entities by potential therapeutic action on the target cell. These poor solubilities and permeability can lead to low bioavailability [3,4]. The anticancer or chemotherapeutic agents are highly cytotoxic to the malignant cell, equally damaging the normal cells. ...
... A positive zeta-potential can target the complex to a negatively charged cell membrane, resulting in effective uptake of the complex [15]. The shapes and sizes of aggregates significantly vary: they can be small unilamellar vesicles of 20-200 nm in size, larger vesicles of 200 nm to 1 µm in size, and giant unilamellar vesicles of more than 1 µm in size [16]. The latter can also exist as multilayer vesicles consisting of numerous lipid bilayers. ...
... The main chemical constituent of liposomes are phospholipids. Phospholipids are amphiphilic molecules characterized by a hydrophilic head that consists of a charged phosphate moiety and hydrophobic tails corresponding to two acyl chains of fatty acids which can be saturated or unsaturated (Kalepu and Betha 2013;Mozafari 2010). In aqueous media, phospholipid molecules self-assemble into a bilayered structure. ...
Liposomes are lipoid vesicles that are closely studied as carriers of drugs to facilitate the delivery of therapeutic agents. Owing to novel liposome technology advances, many liposome-based drug formulations have now been clinically tested, and few of them have recently been licensed for medical application. Reformulation has allowed the therapeutic indices of different agents to be enhanced, mainly by altering their biodistribution. This analysis discusses the possible uses of liposomes in medical administration with examples of clinically accepted formulations and the issues associated with the continued use of this drug delivery system. This chapter focuses primarily on methods that are strictly scalable and also on limitations on the industrial applicability of liposomal medicinal products and regulatory criteria on the basis of US Food and Drug Administration (FDA) and European Medicines Agency (EMA) documents.KeywordsLiposomeDrug deliveryTherapeutic agents
The purpose of this study is to prepare stimuli-responsive chimeric liposomes (i.e. hybrid polymer-lipid liposomes) containing functional copolymers and conduct aqueous solution studies in order to determine their properties and potential as drug-delivery nanocarriers. Two random copolymers, composed of the hydrophilic, pH and thermo-responsive 2-(dimethyl amino) ethyl methacrylate (DMAEMA) monomer and the hydrophobic stearyl methacrylate (SMA) monomer, were synthesized via free-radical polymerization and molecularly characterized using SEC, FTIR, and 1H-NMR. The synthesis was followed by aqueous solution studies, utilising dynamic light scattering (DLS) in order to determine their stimuli responsive self-assembly properties. The preparation of chimeric liposomes was mediated by thin film deposition and hydration, followed by aqueous solution studies via DLS, ζ-potential and fluorescence spectroscopy. The drug-loading studies include curcumin loading via a thin film deposition and hydration technique, while aqueous solution properties of the drug-loaded chimeric liposomes were determined utilizing DLS, and UV-Vis spectroscopy.
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Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI 3 K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper activation of PI3K and Akt is detected in some types of cancer that posses defect in PTEN. Tracking the crosstalk between PI3K/Akt, PTEN and STAT 5A signaling pathways, in cancer could result in identifying new therapeutic agents. The current study, identified an over view on PI3K/Akt, PTEN and STAT-5A networks, in addition to their biological roles in he-patocellular carcinoma (HCC). In the current study galactomannan was extracted from Caesalpinia gilliesii seeds then loaded in liposomes. Liposomes were prepared employing phosphatidyl choline and different concentrations of cholesterol. HCC was then induced in Wistar albino rats followed by liposomal galactomannan (700 ± 100 nm) treatment. Liver enzymes as well as antioxidants were assessed and PI3K/Akt, PTEN and STAT-5A gene expression were investigated. The prepared vesicles revealed entrapment efficiencies ranging from 23.55 to 69.17%, and negative zeta potential values. The optimum formulation revealed spherical morphology as well as diffusion controlled in vitro release pattern. Liposomal galactomannan elucidated a significant reduction in liver enzymes and MDA as well as PI3K/Akt, PTEN and STAT 5A gene expression. A significant elevation in GST and GSH were deduced. In conclusion, Liposomal galactomannan revealed a promising candidate for HCC therapy.
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Evidence from the peritoneal dialysis literature suggests that the peritoneal membrane permeability of a number of hydrophilic anticancer drugs may be considerably less than plasma clearance. Pharrmacokinetic calculations indicate that such drugs administered ip in large volumes are expected to maintain a significantly greater concentration in the peritoneal space than in the plasma The concentration difference offers a potentially exploitable biochemical advantage in the treatment of patients with presumed residual ovarian cancer confined to the peritoneal cavity.
Nowadays the development of new drug delivery systems plays a major role in pharmaceutical industries. The drug delivery practice has been altered in last years and even many advanced innovations happened in recent times. Newer drug delivery technologies are largely influencing the current medical practice. Alterations of a current drug into a new drug delivery technology can positively changing the bioavailability, safety and efficacy of the drug and also it can produce improved patient compliance. At this time, a number of pharmaceutical companies are forwarded to initializing multiple drug delivery technologies for creating excellent advantages, prolonging patent and better outcome for their marketed products. One of the main challenges in newer drug delivery is, huge molecules are rapidly dissolved in the blood volume and they have a lined capacity to cross barriers. Drug delivery technologies can be performed on many available dosage forms like tablets, capsules, pills, injections, suppositories etc. Conventional drug delivery may produce problems regarding oral bioavailability. This can be improved by introducing newer drug delivery techniques like oral controlled drug delivery, site targeted delivery, rate programmed drug delivery, feedback regulated delivery, fastly disintegrating dosage form by oral route, topical and nasopulmonary drug delivery.
Adjuvants can be defined as agents which non-specifically increase immune responses to specific antigens. Some adjuvants, such as alum or Freund’s incomplete adjuvant (FICA, a water-in-oil emulsion), increase the formation of antibodies against protein antigens without the development of delayed hypersensitivity. These can be termed type A (antibody-promoting) adjuvants. Others, such as Freund’s complete adjuvant (FCA, with killed mycobacteria added to the incomplete adjuvant), promote delayed hypersensitivity as well as increasing antibody formation against protein antigens. These can be termed type C (cellmediated immunity-promoting) adjuvants. Evidence has been summarized (1) that many adjuvants exert their effects initially on macrophages and then on helper T-lymphocytes; for these the term T-adjuvants has been proposed. However, some adjuvants, such as bacterial lipopolysaccharide, appear to be able to stimulate B-lymphocytes directly without the agency of T-lympho-cytes; these can be termed B-adjuvants.