Volume 7, Issue 3, March – 2022 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

Anti-Cancer Liposomes
1
Mahira Amirova, 1-2Ellada Huseynova,2Gulnara Vahabova, 3Rena Rahimova, 3Gulnara Dashdamirova
1, 2, 3
Azerbaijan Medical University, Faculty of Public Health, Biochemistry Department, Baku, Azerbaijan
GulnaraVahabova, PhD, Assoc.Prof.,
Ellada Huseynova, PhD, Ass.Teacher,
Rena Rahimova, PhD, Ass.Teacher
Gulnara Dashdamirova, PhD, SeniorTeacher,

Abstract:- Tumor is one of the most wide-spread diseases efficacy. The chemotherapy in tumor is also limited by the
across the planet, and along with this - the first in a row inability to reach required drug concentration in target tissue.
of the working-age population death causes. The However, the application of nanotechnology has led to the
pathogenesis of uncontrolled tissue growth and development of efficient drug delivery systems known as
malignancy is still unexplored, making the tumor one of liposomes. In 1965, it was first demonstrated that
the most difficult, if not curable, diseases to treat. Tumor spontaneously liquid-filled spheres of lecithin allow pass
treatment today is carried out by extremely undesirable monovalent cations and anions; the process occurs similar to
methods, the leading role among which belongs to chemo- the diffusion of ions through a biological membrane
and radiation therapy, the result of which is always [Bangham et al., 1965]. Then Gregoriadis et al. demonstrated
inevitable - death. In this regard, there is an urgent need the possibility of liposomes using for the selective delivery of
to find medicines that can save the lives hundreds of antitumor and antimicrobial drugs to tissues [Gregoriadis,
thousands of people without causing tangible harm to the 1976a]. Liposomes, initially known as spherules, are drug
body. Such drugs can be liposomes, which have long delivery containers presented as vesicles filled with
attracted the attention of scientists in the framework of hydrophobic or hydrophilic reagents coated with
the neoplasia treatment, but still remain at the research phospholipid bilayers. Liposomes are used to deliver unstable
stage due to the high cost and complexity of industrial antimicrobials, anticancer drugs protecting them from
production.Using the data, accumulated to date on degradation. The content of the liposomes is protected from
liposomes and their invasiveness in tumor tissue, we oxidation and degradation with phospholipid shield. Since
propose our own version of liposome production, which, they have low toxicity and are biocompatible, as well as
due to its relatively low toxicity and ease of manufacture, biodegradable, they attract the attention of scientists around
has more chances of being introduced into widespread the world as potential anticancer agents.
medical practice: these are liposomes based on the liquid
phase from Chaga fungus and the lipid phase with Many therapeutic agents are effective only in certain
natural peptides relatively easily extracted from plants concentration. For this reason, liposomal encapsulation, by
and microorganisms. reducing the clearance of drug, increases the time of its
exposure to tumor. Тhe phospholipid barrier protects the
Keywords:- liposome, natural peptides, neoplasia. inner layer of the liposome until the contents of the liposome
are delivered to the destination cell. This allows increase the
I. INTRODUCTION therapeutic effect of the active substance without increasing
the bouquet of side effects. Liposomes make it possible to
An abnormally rapid growth of an abnormal cells vary the selectivity to certain cells of the body, provide a
population is called a tumor. A tumor can be benign or gradual release of the drug, the solubility of hydrophobic
malignant. Cancer is a malignant neoplasm with loss of drugs, and reduce the toxicity of drugs in relation to normal
normal cell morphology. According to the type of cells tissues. İmportant requirements for liposomes are their
affected by the process, carcinoma, sarcoma, lymphoma, biocompatibility, biodegradability, non-immunogenicity,
germ cell tumors and blastoma can be distinquished. non-toxicity and the ability to combine both hydrophilic and
Carcinomas are sort into basal cell carcinoma, transitional hydrophobic compounds. The appeal of liposomes lies in
cell carcinoma, adenocarcinoma, squamous cell carcinoma. their composition making them biodegradable and
Sarcomas are sort to bone sarcoma & soft tissue sarcoma. biocompatible. They are mainly used as carriers of molecules
Lymphoma, as well as myeloma belong to leukaemia types. that can be toxic to the body as a whole or are too labile and
Cancers of brain & spinal cord are in a separate category of can be destroyed by the action of blood plasma enzymes. The
tumors [Alavi M. and Hamidi M., 2019]. Cancer is the duration of their circulation is provided by a change in their
world's leading cause of death, claiming thousands of lives charge, size and lipid composition. Based on the size and the
each year, because the effectiveness of modern treatments for number of bilayers, liposomes can be sort into unilamellarand
various types of cancer is low. Many antitumor agents are multilamellar; the half-life of liposomes depends on the the
highly toxic, which limits their use in treatment. In addition, number of phospholipid bilayers. In unilamellar liposomes,
toxic drugs used in cancer therapy affect both cancer and the liposome has a single layer of phospholipid surrounding
normal cells. А number of cytotoxic chemotherapeutic agents an aqueous solution. In multilamellar liposomes, several
are highly hydrophobic, which contributes to their long-term phospholipid layers separate the aqueous phases from each
accumulation in the body with a subsequent harmful toxic other. Such liposomes, when colliding with the target cell,
side effects on normal organs and tissues, while the exfoliate like cabbage. Sometimes, in multilamellar
chemotherapeutic agents that have a short half-life, have low liposomes, several unilamellar vesicles are encapsulated

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Volume 7, Issue 3, March – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
within a larger liposome, forming drug-filled phospholipid In order to reduce the cost of liposomes and make them
spheres separated by layers of water. The number of bilayers available to the public, inexpensive, natural, readily available
affects the amount of drug contained in the liposomes. anti-cancer extracts should be included in their
composition.This may be the chaga extract, which has
Depending on the total charge, lipid composition and already begun to be used as an antitumor agent. We offer
size, the properties of liposomes can vary significantly. The chaga aqueous extract as an antitumor liposome filler, which
major components of liposomes are phospholipids and is highly bioavailable and easy to obtain [Yakimov P.A. et al.
cholesterol, that are the major constituents of natural 1961]. To prepare an easily accessible extract, Chaga fungus
biomembranes. The choice of lipid composition is also crushed to a diameter2-7 mm is poured with 60 ml of
critical for higher effective loading by the passive method. extractant (purified water) and extraction is carried out in a
The chemical properties of these lipids control the behavior thermostat for 5 hours at a temperature of 70°C. After that,
of liposomes. Unsaturated phosphatidylcholine forms more the aqueous extract is separated from the pulp by filtration,
permeable bilayers, while dipalmitoylphosphatidylcholine obtaining an extract from the first stage of extraction. The
forms a rigid, rather impermeable bilayer structure. Lipids remaining pulp is poured with a new portion of the
can be natural or synthetic; but mostly they are biologically extractantin the amount of 40 ml and extracted for 5 hours in
inert natural phospholipids with low immunogenic a thermostat at a temperature of 70°C. The extract is
activity.Because of the amphiphilic properties of separated from the pulp by filtration, obtaining an extract
phospholipids, liposomes are considered as a versatile drug from the second stage of extraction. The extracts obtained in
carrier container that encapsulate both hydrophobic and the first and second stages of extraction are
hydrophilic drugs. The hydrophobic regions of lipids are combined[Sbezhneva V.G. et al., 1994]. The therapeutic
assembled into spherical bilayers called lamellae. Since lipids effect of liposomes is proportional to the hydrophylic drug
are amphipathic, bilayer phospholipid membrane liposomes volume contained in the nanoparticles. For better
can transport incorporated both aqueous and lipid drugs as incorporation into liposomes, it is preferable to add maclura
target containers. Liposomes consist of one or more lipid [Saloua F. et al., 2009] extract to Chaga fungus water extract
bilayers that stepwise surround an aqueous units, & the polar to obtain negative charge inside liposomes; it should
groups are oriented to internal and external aqueous phases. facilitate the combination & interaction of inner drug layer
Drugs are distributed heterogeneously in liposomes with cationic antitumor peptides. antimicrobial peptides are
dependent on their different solubility: lipophilic drugs are now being actively introduced into medicine in order to
located in the lipid bilayer, hydrophilic drugs are in the provide treatment for intractable diseases; among them there
aqueous phase, and amphiphilic drugs are distributed are also antitumor peptides with high activity and selective
between the lipid and aqueous phases. Encapsulation of effect on the tumor, especially positively charged ones.
lipophilic anticancer drugs can be achieved through Antitumor properties of maclura (McClure)isoflavoneshas
hydrophobic interaction of these molecules with the bilayer been revealed, they are more pronounced in pomiferin[Ni Q.
of the liposomal lipid membrane [Allen, 1998] or by an et al., 2013]. Аctive anti-neoplastic substances from maclura,
active loading [Gubernator, 2011]; hydrophilic pomiferin that is a prenylatedisoflavone and osajin, pass into
chemotherapeutic drugs can be encapsulated by trapping tincture prepared by Sbezhneva V.G.et al.
these drugs within the aqueous phase of the liposome. method[Sbezhneva V.G. et al., 1994], they are able to stop
tumor growth. The McClure fruit is also rich in alkaloids,
All liposomes are prepared in 4 main steps: оbtaining of glucosides, lecithin, vitamin C, and flavonoid pigments
lipids from an organic solvent; dispersion of lipid in an [Saloua F.et al. 2009]. In addition to being anti-carcinogenic,
aqueous medium; purification of the resulting liposome; the Mclure extract has a radioprotectiveeffect which is
analysis of the final product. The methods of drug essential for cancer patients receiving radiation therapy. This
encapsulation into the liposomes can be sort into two will improve the active therapeutic load of liposomes.
subgroups: the passive loading, in which drug encapsulation Hydrophilic drugs, which in our case is chaga&maclura
occur during the vesicle formation process and the active extract, should be loaded into the inner core of liposomes by
loading, in which drug is entrapped after the formation of mixing with a hydrating buffer. The buffer promotes the
vesicles. Passive loading of the drug into liposomes consists formation of a thin hydrated lipid film. Eventually these
of the encapsulation drug present in the hydrophilic phase. drugs will be loaded into lipid bilayers. Chaga water extract
Passive loading methods include the mechanical dispersion molecules not used in the process of vesicle formation should
of the drug, solvent dispersion method and removal of be removed from the liposome suspension using dialysis or
unencapsulated material. Amid mechanical dispersion gel filtration chromatography. The therapeutic power of
methods that include sonication; french pressure cell: liposomes is proportional to the water volume contained in
extrusion; freeze-thawed liposomes etc., sonication is the the lipid bilayer. The efficacy of drug encapsulation depends
most extensively used method. [Akbarzadeh, A. et al., 2013]. on the type and concentration of lipids, the size of liposomes,
The size and polydispersion index of nanovesiclesmay be etc. [Pandey H. et al. 2016]. Since we are producing large
determined by dynamic light scattering, while the 100-250 nm nanoparticles, we can use passive encapsulation
morphology of nanovesicles can be assessed using scanning to reduce the cost of liposomes.
electron microscopy. The capture efficacy сan be determined
by the ratio of the amount of unencapsulatedhydrophylic Let us consider both passive and active targeting of
compounds to the initial amount of initially loaded. liposomes to tumor cells. The active liposomal targeting
means attaching specific ligands to the surface lipids of the
nanoparticle [Federman N et al., 2010]. After active

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targeting, liposomes conjugated with ligands can find their size of 88 ± 5 nm has shown significantly higher growth
target cells. As the ligands, antibodies, antibody fragments, inhibitor effect on A549 human lung epithelial cancer cells
proteins, peptides, aptamers that can specifically bind to along with a sustained drug release after a period of 48 h
various motifs on cancer cell surface may be used. These compared to the free drug. In a similar study, a 50.5%
liposomal-ligand complexes are distributed within the tumor inhibition of the growth of Hodgkin's lymphoma was
tissue via receptor-mediated endocytosis. Some targeting observed with passive delivery of curcumin using liposomes.
ligands used in liposomal nanoparticles to achieve active Passive delivery of temozolomidewith liposomes to
targeting in malignancies are listed below. Inclusion of the glioblastoma and melanoma cells results in higher inhibition
holotransferrin on the surface of the liposome ensures its of proliferation and lower cytotoxicity than without
binding with transferrin receptor on the surface of liposomes. Passive uptake of liposomes predominantly by the
hepatocellular carcinoma, small cell lung cancer, gastric tumor is provided taking into account the characteristics of
cancer cells. Anti-MT1-MMP ligand may bind to MT1- feeding the tumor vascular system. The fact is that the pores
matrix metalloproteinase and can deliver the drug to in the vessels adjacent to the tumor tissue differ significantly
fibrosarcoma cells. Asn-Gly- Arg peptide, also termed NGR from the endothelial pores of normal healthy endothelium.
peptide attaches to another matrix metalloproteinase, namely Overexpression of certain angiogenesis factors by tumor,
aminopeptidase N in malignant cells of such as vascular endothelial growth factor (VEGF), results in
neuroblastoma&Kaposi sarcoma. IgG1 antihuman TfRscFv increased vascular permeability, resulting in increased
ligand binds to head and neck cancer cells, is attached by penetration and retention, due to which there is an effect of
liver, lung, breast & prostate cancer cells [Yingchoncharoen, increased permeability and retention in the tumor sites. That
P. et al., 2016]. Folate receptor of lung multi-drug resistant means significantly less fluid return to the lymphatic system,
carcinoma variant, oral carcinoma or squamous cell oral due to which liposomes up to 400 nm in size can effectively
carcinoma, folate receptor expressing lymphoma, lung accumulate in tumor foci. Particles larger than 400 nm are
carcinoma, and mouse lymphoma cells can be attached to characterized by difficult penetration into the vessels
incorporated onto surface of liposomes folate [Tyagi N and [BaruaS. &Mitragotri, S., 2014] and for this reason, it will be
Ghosh PC, 2011]. The CD44 receptor of Lewis lung difficult to achieve an increase in their concentration in the
carcinoma, adenocarcinoma, colon carcinoma, melanoma, intercellular substance surrounding the tumor, and treatment
leukemic cells can be a target for liposomes carrying in this case will be ineffective, no matter how active the
hyaluronic acid on their surfaces İn breast cancer, substance included in the liposome is. Maeda H. states that
glioblastoma are selected liposomes with Anti-EGFR- high molecular weight drugs accumulate in large quantities
antibody that can attach to Anti-EGFR.HER2 of EGFR preferably in tumors. He coined the term "enhanced
family is a target for Anti-HER2 scFvantibodes on surface of permeability and retention” effect [Maeda H., 2012]. Like the
liposomes aimed lymphoma, gastric & breast carcinoma. tumors they nourish, tumor vasculature is also immature &
VCAM-1 on the surface of ovarian cancer and multiple disorganized, and chaotic. In solid tumors, the capillary bed
myeloma cells can bind to anti-VCAM monoclonal is built with a set of branching structures adjacent to vessels
antibodies. Innovations in the production of liposomes start of disorganized size composed of loosely attached
with the use of aptamers in the production of ligands. Thus, endothelial cells lacking pericyte support. Tumor vessels
Sgc8 aptameris used as ligand to tyrosine kinase 7 present on have large endothelial fenestrations ranging from 100 to 600
the surface of ill T-cells in acute T-cell lymphoblastic nm, which is why the permeability of tumor capillaries
leukemia & shows early onset of tumor inhibition. In liver increase. There are reports, that the new tumor vessels
cancer, siRNA targeting VEGF and/or siRNA targeting developed during angiogenesis are irregularly shaped with
kinesin spindle protein binds to VEGF. αvβ3 integrin is a discontinuous epithelium and range in size from 200 to 2000
target for Arg-Gly-Asp ((RGD peptide ) peptide in liposomal nm [Pethe A. et al., 2018]. This in turn, leads to effusion of
treatment ofmelanoma. [Yingchoncharoen, P. et al., 2016]. plasma proteins into the tumor and increased pressure in the
intercellular matrix of tumor tissue. Using the "enhanced
Of course, the targeted delivery of liposomes with permeability and retention” effect, high molecular weight
ligands implanted in them seems more attractive, but let's not liposomes can be designed to preferentially penetrate tumors.
forget that today a tumor is one of the most common To do this, liposomes must have an optimal diameter that
diseases, and we are obliged to treat both socially well-off allows them to overcome the vascular endothelial barrier and
and low-income patients. The main disadvantage of penetrate into the tumor interstitium. From this point of view,
liposomes active targeting is the lack of cheap manufacturing the size of liposomes is of great importance. We should keep
methods leading to the high cost. Therefore, the choice of a in mind that fenestrated capillaries are found wherever active
method of passive drug delivery to target cells, based on the filtration or absorption occurs: small intestine, endocrine
characteristics of malignantly modified tissues, seems more glands, kidney. The vessel fenestration found in muscles,
appropriate. In this work, we consider a method for skin, lungs, connective tissue and these endothelial cells
manufacturing the cheapest liposomes using a medicinal contain pores between cells 50-60 nm & are more permeable
substance obtained from a cheap available natural than other normal vessels. Discontinuous endothelial cells
compounds. found in the spleen and liver have pores up to 100 nm wide.
This means that liposomes with less than 100 nm wide can
The strategy for creating cheapest liposomes is based on cumulate in normal tissues, while those that are too large
their passive absorption by the tumor tissue. There are (>250 nm) will not be able to pass through the all desired
several reports of passive targeting by liposomes. For fenestrations of tumor endothelial cells. Additionally,
example, sclareol-loaded liposomes with an average particle

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liposomes that are too small (10 nm) will be quickly filtered Ohsaki Y. et al., 1992]. The mechanism of action of some of
out by the kidneys, there are also some reports about them is based on the activation of immune cells in order to
effective extravasation of vesicles with less than 200nm destroy tumor cells [Zhang, L.et al., 2019]; on the other hand,
diameter. Considering all mentioned above factors we state they destroy tumor cells by inducing necrosis or apoptosis in
that when creating liposomes, the diameter may be larger them [Kim JY et al., 2018]. Magainin also inhibits
than 100 nm but not exceed 250 nm. This will facilitate the angiogenesis, prevents the formation of a vascular network
penetration and retention of dosage forms in the tumor tissue, that nourishes tumor tissue, and prevents metastasis [Al-
while ensuring minimal invasiveness in healthy tissues. Benna S. et al., 2011]. Another important mechanism of
action of antineoplastic peptide magainin is based on the fact
When considering the utilization of liposomes by tumor that it disrupts these processes by interfering with gene
tissue, it should be taken into account that liposomes interact transcription and translation in the tumor cell [Huan, Y. et al.,
with cells mainly in the following ways: formation of 2020].
electrostatic bonds and hydrophobic bonds with cell
membrane motifs; endocytosis by cells of the Antimicrobial peptides directed against the tumor and
reticuloendothelial system, namely neutrophils and naturally produced in organisms are distinguished by a high
macrophages; fusion of the lipid bilayer of the liposome with positive charge, provided by the additional arginine and
the plasma membrane. Due to this, the fate of liposomes lysine residues in them. Butarginine & lysine may cause
largely depends on the charge of its surface. Z- potential hemolysis and, additionally, a large number of cationic
determines the total surface charge of liposomes, i.e., liposomes can lead to an inflammatory tissue response
whether the liposome is cationic, anionic, or neutral in because highly charged liposomes, either positively or
nature, since depending on the component used, liposomes negatively charged, can fix complement proteins [Federman
can be neutral, negatively or positively charged. Charge is N. & Denny C., 2010]. He et al. state that even when absolute
also important in the design of the tumor-targeting liposomes, zeta potential values were identical in nanoparticles,
because it can affect their circulation time and the potential macrophages phagocytized a higher percentage of positively
for enhanced permeability. Anionic liposomes have the charged nanoparticles compared to the negatively charged
advantage of reducing self-aggregation in suspension and [He et al. (2013]. Therefore, to prolong the action of the
increasing non-specific cellular uptake. But this is true when liposomes on the body, it is also advisable to use
it comes to cells without neoplasia. It has been established, antimicrobial peptides with the introduced into them
that the tumor cell carries an additional negative charge on its histidine, since it has a variable polarity and the ability to
surface due to an excess of phosphatidylserine.Normally, rearrange the charge depending on the charge of the
phosphatidylserine is located on the inner surface of the molecules it interacts with. Currently, developments are also
plasma membrane facing the cytoplasm [Schutters K. underway to obtain artificial antimicrobial peptides with the
&Reutelingsperger C., 2010]. After the neoplastic process inclusion of histidine, which does not cause hemolysis, can
starts, this selectivity is lost [De M. et al., 2018], De M. acquire a positive charge interacting with cell membranes,
etal.report that a phosphatidylcholine-stearylamine (PC-SA), has buffer properties at physiological pH, providing
induced apoptosis in majority of cancer cell lines. The amphiphilicity and, therefore, a sufficiently high toxicity at
change in charge on cancer cell surface allows the low hemolytic properties of peptides, in which it is included.
components of innate immunity, the antimicrobial peptides, To reduce the high cost of liposomes, it is recommended to
to recognize tumor-modified cells. Such natural-derived include highly specific and cheap antimicrobial peptides into
antimicrobial peptides can replace expensive ligands and liposomes. In the case of tumor therapy, cationic liposomes
provide additional retention of drug-laden liposomes in the will be better absorbed, however, small cationic liposomes
site of neoplasia.To neutralize negatively charged Maclura can be excreted by the kidneys, which have the ability to
vinegar extract in the core of liposomes we need cationic filter positively charged particles. А significantly large size
compounds, which would significantly increase of liposomes can solve this problem and prevent drug loss
encapsulation efficiency due to enhanced active interaction through the kidneys. Neutrally charged liposomes have the
between agents. The introduction of cationic antimicrobial longest circulation time but tend to aggregation, which may
peptides with antineoplastic properties, such as magainin2, limit their penetration into the tumor vasculature. This
should facilitate the formation of liposomes, enhance the problem may be easily solved by incorporation histidine-
therapeutic effect, and increase the affinity to the tumor containing antimicrobial peptides into the shell of liposomes.
[Boohaker R. J.. et al., 2012].It is possible to load the drug
into liposomes using the active loading method, but this will The binding of charged liposomes to oppositely charged
increase the cost of the drug and accordingly, reduce the cell molecules can be controlled by changing the zeta
scope of its application. Magaininantimicrobial peptides drug potential of the liposomes [Smith MC et al., 2017].
development was founded by Magainin Pharmaceuticals Polyethylene glycol is another widely used liposome
(later called Genaera). Single magainin 2 was found to form component, because it increases circulation time due to its
pores ~2.8 nm in diameter in B. megaterium and translocated stealth properties. But polyethylene glycol significantly
into the cytosol. The peptide significantly disrupted the cell affects the zeta potential of liposomes: it is –43 mV in
membrane, allowing the penetration of a large molecule into liposomes without polyethylene glycol, but decreases with an
the cytosol, which was accompanied by membrane budding increase in the content of this polymer, and can drop to –5
and lipid turnover, mainly accumulating in mitochondria and mV. In this regard, it is appropriate to recall the effect of
nuclei [Imura Y. et al., 2008]. Such antineoplastic peptides as cholesterol on the zeta potential. JovanovićА.еt al. in 2017
magainin inhibit the growth of tumor tissue in various ways [ studied the effect of different cholesterol content (0-50

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mol.%) on membrane fluidity, vesicle size, and zeta potential movement of phospholipids in membranes.The rigidity of
of liposomes. They declare thatthe z-potential was negative membraneimparted to liposomes by сholesterol reduces the
in all cholesterol-incorporated liposome samples, and the leakage of encapsulated drugs.The percentage of cholesterol
highest absolute moduli were achieved at 50 mol % also affects the final phase transition temperature of the
cholesterol in the sample. But Aramaki K. et al declare bilayer. Some studies have shown that cholesterol helps to
cationic liposomes can be prepared by mixing cationic protect the lipid bilayer from hydrolytic degradation. Sterols
surfactants with phospholipid liposomes, but their such as ergosterol, stigmasterol, lanosterol, β-sitosterol and
cytotoxicity will be high enough. Aramaki K. et al. claim that cholesterol have been added to liposomes both to reduce
mixing quaternary ammonium monoalkyl and dialkyl membrane fluidity and increase the stability of the
chlorides or cholesterol with cationic liposomes increased the phospholipid bilayer and to reduce leakage of encapsulated
zeta potential of the liposomes from negative to positive active compounds.Аs a result of the interaction of cholesterol
values (more than +50 mV). Cholesterol also shifts the with membrane phospholipids, membrane adhesion
negative-positive transition point of the cationic fraction increases, passive permeability for small molecules
[Aramaki K. et al., 2016]. Optimum stability and fluidity decreases, which ensures the preservation of the drug inside
were also achieved with 50 mole % cholesterol in the lipid the liposome until the moment of interaction with the
phase. components of the tumor tissue, since cholesterol decrease
the permeability of the bilayer for both non-electrolytic and
Increasing of cholesterol in the liposome membrane can dielectrolytic solvents. There is also a direct relationship
increase the size of liposomes. Cholesterol provides between the cholesterol content of liposomes and the value of
membrane fluidity, elasticity, permeability and stability to the gel-to-liquid transition temperature. It was reported, that
liposomes. JovanovićА.Et al. (2017) found that an increase in when sterols are added, the Tm of the crystalline phase,
the cholesterol content in liposomes also reduced their which characterizes the transformation of the gel into a
fluidity and increased rigidity. Аt the highest cholesterol liquid, decreases. Сholesterol as a non-ionic molecule
content (50 mol.%) significantly larger liposomes were increases the highest zeta potential of cationic liposomes.
obtained. Cholesterol can reduce the interaction of liposomes
with certain proteins, making them less susceptible to II. CONCLUSION
phospholipase. This reduces the loss of phospholipids from
liposomes and high density lipoproteins, and inhibits their  The optimal liposome size for tumor targeting is 100-250;
digestion by macrophages. The cholesterol incorporation into  Chaga and Maclura extracts mixed with cationic
liposomes inhibits their uptake by reticuloendothelial cells, antimicrobial peptides can promote the emergence of stable
and also reduces their interaction with certain proteins, liposomes with active electrostatic interactions in the
affecting the uptake of liposomes by tissues. Freedom of liposome core;
rotation due to flipping motions in phospholipids creates  Passive binding of liposomes requires the presence of a
liposomes with leaky properties. Cholesterol is the main negative charge on its surface, and the inclusion of
component stabilizing the phospholipid bilayer of liposomes cholesterol in a ratio of 50 Mol%of all lipid compounds is
& preventing liposomes aggregation. Depending on the the most appropriate.
cholesterol content, the rigidity and fluidity of the
phospholipid bilayer change as follows. When the mole  Authors' Contribution:
fraction of sterol is 30-45% of the total liposome All authors have accepted responsibility for the entire
components, this provides optimal membrane fluidity and content of the submitted manuscript and have approved it.
rigidity, along with good elasticity and permeability of the
liposomes. However, it is too early to say that the optimal  Research funding: none.
concentration of cholesterol has already been clarified. The Honorarium: none.
maximum amount of cholesterol that can be introduced into
the bilayers is nearly 50 mol%. Depending upon the rigidity  Competing interests:
and fluidity of bilayer, the molar percentage of cholesterol No funding agencies played any role in the design of the
varies from 30-45% of total liposomes components study; in collecting, analyzing and interpreting data; when
[Magarkar, A. et al., 2014]. By the way, the concentration of writing a report; or in a decision to submit a report for
cholesterol in the normal cell membrane is about 30–50 publication.
mol% of all lipid compounds. The most commonly used ratio
 Acknowledgements.
of phospholipids to cholesterol is 2:1, or 1:1 ratio. When
The authors sincerely thank Miss Emily Margaret,
assembling liposomes, the only polar group of cholesterol (-
“Meetings International” Program Manager, for her
OH group) is immersed in the polar head layer of the
support and active assistance in the publication of the
phospholipids in lipid bilayer. The rest cholesterol structure
article, skillful coordination and communication with the
is the hydrophobic fused ring of
journal.
cyclopentaneperhydrophenanthrene immersed in the interior
of the lipid bilayers. The sterol carbohydrate tail at position
C17 is also mixed with hydrophobic fatty acyl chains.
Cholesterol makes the bilayer structure more compact and
serves to fill the gap created by the imperfect packing of
phospholipid molecules. The incorporation of cholesterol into
phospholipid bilayers reduces the flip-flop and lateral

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