Liposomes: A Novel
Drug Delivery System: An Overview
Nikita R. Nikam*, Priyanka R.
Patil, Mr. R. R. Vakhariya, Dr. C. S. Magdum
Rajarambapu College of
Pharmacy, Kasegaon, Tal- Walwa Dist- Sangli, Maharashtra
*Corresponding Author E-mail: nikitanikam@gmail.com
ABSTRACT:
The search for
liposomes or lipids was performed on self-generated bilayer lipid hydrations.
The liposome drug delivery system has played an important role in the formation
of powerful drugs to improve treatment. Recently, the symptoms of liposome
formulations decrease symptoms and increase conservation at the target site.
Liposomes are also used in cosmetic formulations. Liposomes are described in
terms of physical, chemical and biological parameters. New developments in this
area are the specific binding properties of agglutinating liposomes with target
cells such as tumor cells and specific molecules in the body. This review will
help researchers working in the field of lymphocytosis. Distribution this
article provides an overview of the drug delivery system in the form of
liposomes. He focused on
classification, mechanisms, types of comedic liposomes and applications on
liposome drug delivery systems.
KEYWORDS: Liposomes
formulations, lipid bilayer, Characterization, Cosmetics.
INTRODUCTION:
Antineoplastic
cytotoxic agents for the vitamins of tumor cells also affect normal cells.
Indeed, their low index of improvement (TI) means that the dosage essential to
obtain the effect of the tumor is toxic to normal cells. These drugs are
targeted at a particular site (diseased sites), so their toxic effects are
reduced to less than one tissue1. Therefore, the most effective drug delivery system
administered at the targeted site is required. The support of nanoparticles,
microparticles, polysaccharides, conferences and liposomes can be used to
monitor specific sites.2-3
When
phospholipids are extracted in water, they automatically form a closed
structure and as the membrane bilayer phospholipid in internal aqueous
environments, this system is called liposomes4. Generally, the
liposomes are fixed in the form of spherical flasks with a particle size
ranging from 30 nm to several micrometers. Liposomes are widely used as
carriers for countless molecules in the cosmetic and pharmaceutical industries.
In
addition, the agrifood industries have studied the use of liposomes
encapsulation to increase the number of delivery systems that can compensate
for volatile compounds (e.g., antimicrobials, antioxidants, flavorings, and
bioactive components) and preserve them efficiency. Liposomes can trap
hydrophobic and hydrophilic compounds avoid disturbing the detached configuration
and get stuck on specific targets.
Cosmetic is basically an active ingredient in cosmetic products that may contain medicinal benefits such as drugs or medicines5. The use of racks in products mainly works in five types: purification, decoration, care, hydration and protection that will help beautify the skin. Career technology, which includes nanoparticles such as liposomes, solid lipids, nanoparticles, niosomes, etc. The drugs help in the absorption, absorption and reduction of toxicity caused by high doses.6 The main reason for doing liposome research is that the fact that liposomes can mimic biological cells can be mainly attributed to liposomes. This means that liposomes are extremely biocompatible, i.e. enzyme, antibacterial, antiviral, antiparazine, fungicide, transdermal transporters, diagnostic tools and a subsidiary for vaccination.7
History:
After
testing and analyzing phospholipids in water under the electron microscope D.
Bungham and his colleague R. W. The first description of liposomes was
described by Thorn in 1964. They discovered that
phospholipids are automatically defined as they are called "bag-shaped”.
Gerald Weissman, a close associate, should be called structure, called
liposomes, which they later defined as "microscopic capsules composed of
one or more lipid bilayer". This research focused on a large number of
searches. The substances used in liposomes are widely used and include the drug
delivery system for cosmetics.7
Liposomes
are designed to achieve the following optimized properties:
1. Control and control of drugs without drugs
2. Quickly overcome the clearance of
liposomes
3. Intracellular distribution of drugs
4. Ligand-targeting liposome
receptor-mediator endocytosis
5. Publication triggered
6. Nucleic acid and DNA distribution8
Classification
of Liposomes:
Figure 1: A
simplified illustration production methods of Liposomes7
Liposomes are
classified on the basis of: 4, 9
1. Structure
2. Method of
preparation
3. Composition and
Application
4. Conventional
liposome
5. Specialty
liposome
Classification Based on Structure:
Table 1: Vesicle Types with their
Size and Number of Lipid Layers
Vesicle Type |
Abbreviations |
Diameter Size |
No. of Lipid Bilayer |
Unilamellar vesicle |
UV |
All size range |
One |
Small Unilamellar vesicle |
SUV |
20-100 nm |
One |
Medium Unilamellar vesicle |
MUV |
More than 100nm |
One |
Large Unilamellar vesicle |
LUV |
More than 100nm |
One |
Giant Unilamellar vesicle |
GUV |
More than 1 micro meter |
One |
Oligolamellar vesicle |
OLV |
0.1-1 micro meter |
Approx. 5 |
Multi vesicular vesicle |
MV |
More than 1 micro meter |
Multi compartmental structure |
2. Based on Method
of Preparation
Table 2: Different
Preparation Methods and the Vesicles Formed by these Methods
Preparation Method |
Vesicle Type |
Single or oligolamellar vesicle made by reverse phase evaporation method |
REV |
Multi lamellar vesicle made by reverse phase evaporation method |
MLV-REV |
Stable plurilamellar vesicle |
SPLV |
Frozen and thawed multi lamellar vesicle |
FATMLV |
Vesicle prepared by extrusion technique |
VET |
Dehydration- Rehydration method |
DR V |
3. Based on
Composition and Application
Table 3: Different
Liposome with their Compositions
Type of Liposome |
Abbreviation |
Composition |
Conventional liposome |
CLs |
Neutral or negatively charge phospholipids and cholesterol |
Fusogenic liposome |
RSVE |
Reconstituted sendai virus envelops |
PH sensitive liposomes |
- |
Phospholipids such as PER or DOPE with either CHEMS or OA |
Cationic liposome |
- |
Cationic lipid with DOPE |
Long circulatory liposome |
LCL |
Neutral high temp., cholesterol,5-10%PEG,DSP |
Immuno liposome |
IL |
CL or LCL with attached monoclonal antibody or recognition sequences |
4. Based Upon
Conventional Liposome:
1- Stabilize
natural lecithin (PC) mixtures
2- Synthetic
identical, chain phospholipids
3- Glycolipids
containing liposome
5. Based Upon
Specialty Liposome:
1- Bipolar fatty
acid
2- Antibody
directed liposome.
3- Methyl/
Methylene x- linked liposome.
4- Lipoprotein
coated liposome.
5- Carbohydrate
coated liposome.
6- Multiple
encapsulated liposome.
Figure
2: Illustration of the basic form the lipid bilayer forms in an aqueous solution7
Mechanism
of liposome preparation:
Liposomes are at the origin of phospholipids, an amphipilic molecule (hydrophilic head and hydrophobic tail). The hydrophilic segments are mainly water-soluble phosphoric acid molecules, while there are two fatty acid chains in the hydrophobic region, where there are 10 to 24 carbon atoms and 0 to 6 double bonds in each series1, 10.
When these phospholipids are dispersed in an aquatic environment, they
form lamellar leaves so that if the polar group of the head is on the aquatic
side of the aqueous zone, the fatty acid groups face each other and are
eventually formed like structures called liposomes. The polar part remains in
contact with the aquatic region with the protection of the non-polar zone
(centered on the surface of the flag) 1, 11.
Mechanism:
There
are several methods by which liposomes act inside and outside the body, they
are:
1- The liposome connects to the cell membrane
and appears to release its contents into the cell.
2- Sometimes they pass through the cell and
their phospholipids are included in the cell membrane through which the drug
blocked inside is released.
3- In the case of phagocytic cells, the liposomes are removed, the walls of the phospholipids are administered by organs called Liposomes and active drugs are released4, 12.
Steps
involved in liposome activity during drug administration:
1.
Endoscopy: Absorption between liposomes in cell membranes causes
contact on the cell membrane.
2.
Endocytosis: Pasteurization of liposomes on the surface of the
cell and wastewater and insertion into liposomes.
3.
Fusion: The lipidyl cell fibers with lipid cell membrane and
lipid bilayer fusion with lipids interfere and the liposomal content in the
septalizem is directly distributed.
4.
Lipid exchange: Lipid transfer proteins in the cell membrane easily
identify liposomes and allow lipid exchange due to the similarity of the
liposomal lipid membrane with the phospholipids of the cell membrane.8
Method of liposome
preparation and drug loading:
The
following methods are used for the preparation of liposome:
1.
Passive loading technique
2.
Active loading technique.
Passive
loading techniques include three different methods:
1.
Mechanical dispersion method.
2.
Solvent dispersion method.
3.
Detergent removal method.13-14
Mechanical
dispersion method:
Sonication:
Sonication
is probably the most widely used method for creating an SUV. Here, MLV,
Sonication is performed without a bath-type sounder or probe sounder in an
inactive environment. The main drawbacks of this process are the presence of a
very low internal volume / disability efficiency, the possibility of compiling
phospholipids and compounds, the elimination of large molecules, probe scores,
and metal pollution MLV with SUV13.
There
are two Sonication techniques:
A)
Probe Sonication:
The
note of the sonicator is direct indirect dispersion in the liposomes. The
energy input into the lipid dispersion is much higher in this method. The
energy connection at the tip generates local heat; therefore, the texture must
be mixed with water / ice during plowing. Up to 1H, up to 5% of lipids can be
de-activated. In addition, with the sonicator probe, Titanium will be released
and the solution polluted.
B) Bath Sonication:
The dispersion of liposomes in the cylinder is placed in a sniper bath.
Controlling the temperature of the lipid dispersion is generally easy in this
process, against the Sonitake using an active tip. Ultrasound treated material
can be stored in sterile texture, under probe units or in an inert environment.15.
French
pressure cell (extrusion):
French
pressure cell involves the extrusion of MLV through a small orifice13.
An important feature of the French press vesicle method is that the proteins do
not seem to be significantly pretentious during the procedure as they are in
sonication. An interesting comment is that French press vesicle appears to
recall entrapped solutes significantly longer than SUVs do, produced by
sonication or detergent removal16.
The
method involves gentle handling of unstable materials. The method has several
advantages over sonication methods. The resulting liposomes are rather larger
than sonicated SUVs. The drawbacks of the method are that the high temperature
is difficult to attain, and the working volumes are comparatively small (about
50 mL as the maximum) 16-17.
Freeze-thawed
liposomes:
SUVs are slowly frozen and thawed gradually. Short-term sonication
disperses the collected ingredients in the LUV. Due to the fusion of SUVs in
the freezing and thawing processes, it is a question of creating Unilamellar
Vesicles. This synthesis is strongly limited by the increase in phospholipid
concentration and the increase of the ionic strength of the medium. 20 to 30%
of insusction effects were received18-19.
Solvent
dispersion method:
Ether
injection (solvent vaporization):
The soluble lipid solution in the diethyl ether or ether-methanol
mixture is gradually being injected to aqueous solution of the material filled
with temperature ranging from 55 ° C to 65 ° C or less. Liposomes are formed by
removing the ether below the vacuum. The main misuse of the technique is that
the population is uniform (70 to 200 nm) and the appearance of frozen compounds
in organic solvents in high temperatures 20-21.
Ethanol
injection:
The lipid solution of ethanol is rapidly exposed to a large buffer. Once
MLVs are created, abuse of this method is that the population. Liposomes are
very thin, it is difficult to remove all the ethanol because they are formed in
the agozotope with water and the probability of being inactivated in various
biologically active macromolecules is the slightest presence of ethanol22.
Detergent
removal method (Dialysis):
The detergents used on their severe microdel concentration (CMC) are
used to dissolve the lipids. Detergent detaches, closes in measure
phospholipids, and finally creates Eluvi. Detergent was removed by dialysis23-24.
A commercial device called Lipopoere (Dicema AG, Switzerland), which is a
version of Dialysis System, is available to remove detergents.
Dialysis bags can be widely used in detergent-free buffer (balanced dialysis)
dialysis 25.
Detergent
removal of mixed micelles (absorption):
Get detergent absorption by moving a mixed mile solution with Bead
Organic polystyrene absorbers such as XAD-2 Mani and Bio-Modes SM2. The biggest
advantage of using detergent absorbers is that they can remove low CMC
detergents, which do not completely reduce.
Liposomes:
Novel Approach in Cosmoceuticals:
Now one day people are searching for products that will provide maximum
returns Minimal effort This kind of cosmetic search is not only for females but
also for male Products are cosmetics, which are products that are designed for
the body Clean up, beautify or make changes and enhance attractive features6.
Liposomes are used in most aquatic systems. Due to fragrances, botany
and virus disinfection, lipstick, deodorants, antiperspirants, and body spray,
20-30 microspheres use polymer structures in liposomes. The loss of liposome is the loss of oxidation and deformation
or structure. This can be solved by optimizing the storage position of this
problem or using anti-oxidants in fraudulent and fraudulent cases26.
Benefits of using
liposome in cosmetics:
The
main benefits of using liposomes are they are able to nourish the skin Collagen
production also helps to improve the flexibility of the skin. The use of
liposomes gives benefits in many ways by increasing the stability, Action
Restore, Biodegradability, Biocompatibility and Extended and Skinny Skin
Releases. The uniformity of the structure with its small size and skin makes it
easy to access fixing skin on the outer layer of the skin also helps in the
skin's substrate Epidermal skin of skin and frozen drug in the skin layer. At
the same time, the problems rapid expulsion of medicines can also solve flammable
sunlight products Liposome-enveloped UV filters are water-resistant.27
Characterization: 28-37
A. Biological
Characterization:
Table 3: Biological
Characterization Parameters and Instruments used for analysis
Characterization Parameter |
Instrument for Analysis |
Sterility |
Aerobic/anaerobic Culture |
Pyrogenicity |
Rabbit fever response |
Animal Toxicity |
Monitoring survival rats |
B. Chemical Characterization:
Table 4: Chemical Characterization
Parameters and Instruments used for analysis
Characterization Parameter |
Instrument for Analysis |
Phospholipids concentration |
HPLC/Barrlet assay |
Cholesterol concentration |
HPLC / cholesterol oxide assay |
Drug concentration |
Assay method |
Phospholipids per oxidation |
UV observance |
Phospholipids hydrolysis |
HPLC/ TLC |
Cholesterol auto-oxidation |
HPLC/ TLC |
Anti-oxidant degradation |
HPLC/ TLC |
PH |
PH meter |
C. Physical
Characterization:
Table 5: Physical Characterization
Parameters and Instruments used for analysis
Characterization parameter |
Instrument for analysis |
Vesicle shape, and surface morphology |
TEM and SEM |
Vesicle size and size distribution |
Dynamic light scattering, TEM |
Surface charge |
Free flow electrophoresis |
Phase behavior |
DSC, freeze fracture electron microscopy |
Percent capture |
Mini column centrifugation, gel exclusion |
Drug release |
Diffuse cell/ dialysis |
APPLICATIONS:
Site-avoidance delivery:
Corticobacterial
cytotoxicity may be considered as a general remedial index (TI) in normal
tissues. In such cases, TI may be modified by encapsulating liposomes to normal
cells by reducing drug delivery. Free doxaryribicin has a severe adverse effect
on heart disease, but when it is prepared as liposomes, reduces the poisoning
without any change in therapeutic activities.1, 38-39.
Site specific targeting:
The
distribution of large quantities of medicines to the desired (diseased) site
can be achieved by site specific targeting by reducing the normal tissue
medication. In order to obtain safe and effective therapy, the drug's active
and inactive targets can both be used to enforce the drug in liposomes.39.
Intracellular drug delivery:
Cytosol
(which drugs are present in the receptors) strengthens the drug, can be used by
the liposomal drug delivery system. N- (Phosphonacetel) -L-Aspartate (Pala)
usually worsens in the cell. After overlapping liposomes, such medicines show
more activity than ovarian tumor cell lines, rather than free medicines. 40.
Sustained release drug
delivery:
Liposomes
can be used to provide medication continuously, which requires long-term plasma
concentration on therapeutic levels to get the optimum therapeutic effects.
Drugs such as cytosine arbinides can be stored in continuous liposomes and
increase the amount of drug free withdrawal in the Vivo.41.
Intraperitoneal
administration:
Intra-peritoneal (IP) can be administered by administering
developed tumor medicines through the IP and treated cavity. From there, there
is a relatively low density of medicines in the disease that results from
accelerated cavity of medicines. However, compared to free medicines, liposomal
incontinence medicines have a lower clearance rate and can be provided with
maximum amounts of medicines for prolonged on target site.42-43.
Immunological adjuvant in
vaccines:
Liposomes
can be enhanced by an antipsure to increase the depression response. Depending
on the antibiotic lipophilic, the liposome may insert antibiotics in the water
bowl or include it in the billiards. Liposomes have been used as the first
immunological agents to increase the immunity response to diphtheria toxide 44.
Pulmonary
Application:
The distribution of
liposomes has been explored as a target selection option for systemic
administration of astrophatic and antigenic compounds and targeted antibiotics
lung infections.
Liposomes are useful tools for the distribution of the lungs because of
the density of their waste; the waste products are more viable for airwaves.
Their biodegradability Long-term lung home stays in danger from allergies or
other side effects 45-46.
Cancer Therapy:
Cytotoxic
medicines can generally be distributed throughout the body, normal and
hazardous cells can die, which can lead to various toxic side effects. The use of these drugs in liposomes increased the life
of the symposiums, the increase in the number of infected tissues, the
protection of medicinal metabolism, the replacement of the drug tissue, and in
mononuclear phagocyte cells (increased liver, spleen and bone-enhancing
organisms increased in the medulla) and decreased kidney, myocardium and brain
To fall To target the tumor, liposomes must be able to release the blood and
enter the tumor45.
CONCLUSION:
Many
drug peddlers who are highly effective and have low heritable signs so keep
targets on the diseased sites using the liposomal drug delivery system.
Medicines containing liposomes can be significant altered pharmacokinetics in
the encapsulated. The effectiveness of liposomal formulation depends on its
ability to distribute phosphorus on prolonged targeted sites and simultaneously
reduce its toxic effects. These events will
hopefully protect against future overlapping and unrealistic ideas and
assurances, and liposomes will move forward in another high productive and
innovative phase of research. From this article, we've completed or understood
all the information about liposomal drug delivery systems, classification,
methods of preparation and their applications.
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Received on 27.01.2020 Modified on 18.02.2020
Accepted on 28.02.2020 ©Asian Pharma Press All
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Asian J. Pharm. Res. 2020; 10(1):23-28.
DOI: 10.5958/2231-5691.2020.00005.2