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Liposomes Notes NT

The review article discusses liposomes as a drug delivery system, highlighting their structure, classification, preparation methods, and applications. Liposomes, which are spherical vesicles made of phospholipid bilayers, are effective in encapsulating both hydrophilic and hydrophobic drugs, thereby enhancing targeted drug delivery while minimizing side effects. Despite their potential, challenges remain in their production and development due to complex and costly processes, necessitating further research in the field.

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0% found this document useful (0 votes)
42 views10 pages

Liposomes Notes NT

The review article discusses liposomes as a drug delivery system, highlighting their structure, classification, preparation methods, and applications. Liposomes, which are spherical vesicles made of phospholipid bilayers, are effective in encapsulating both hydrophilic and hydrophobic drugs, thereby enhancing targeted drug delivery while minimizing side effects. Despite their potential, challenges remain in their production and development due to complex and costly processes, necessitating further research in the field.

Uploaded by

mary latha
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd

Farooque et al Journal of Drug Delivery & Therapeutics.

2021; 11(5-S):149-158

Available online on 15.10.2021 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics


Open Access to Pharmaceutical and Medical Research
Copyright © 2021 The Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0
which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided
the original author and source are credited

Open Access Full Text Article Review Article

Liposomes as Drug Delivery System: An Updated Review


Faisal Farooque 1*, Mohd Wasi 2, Mohd Muaz Mughees 1
1 Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India-202002
2 Department of Botany, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India-202002

Article Info: Abstract


_________________________________________ ______________________________________________________________________________________________________
Article History: The liposomes were the first Nano medicine to be accepted for clinical use. They are the
Received 09 August 2021 spherical vesicles that possess mid empty aqueous space, which is encircled by a
Reviewed 19 September 2021 phospholipids bilayer. Liposomes have immense capability to prevent the degradation of
Accepted 21 September 2021 drugs, reduce side effects and are thus increasingly used for targeted drug delivery. The
Published 15 October 2021 drugs can either be incorporated inside the aqueous space (hydrophilic drugs) or inside the
_________________________________________ phospholipids bilayer (hydrophobic drugs) of liposomes for the targeted drug delivery.
Cite this article as: Considering the importance of liposomes as a drug delivery system, the present review paper
tries to look into its details. The entire paper is classified into six parts. The first part is
Farooque F, Wasi M, Mughees MM, Liposomes as introductory. The second part discusses the classification of liposomes. In the third segment,
Drug Delivery System: An Updated Review, Journal
the structural components of liposomes are detailed. The fourth portion of the paper talks
of Drug Delivery and Therapeutics. 2021; 11(5-S):
149-158 about methods of preparation of liposomes. In the fifth segment, the characterization of
liposomes is discussed. The sixth part discusses the application of liposomes and the last part
DOI: http://dx.doi.org/10.22270/jddt.v11i5-S.5063 is given to concluding observation. Literature shows distinct types of liposomes, categorized
_________________________________________ based on size, number of lipid layers, composition and preparation method. They are recently
used for various nanoscale drugs formulation and a piece of concrete evidence was seen
*Address for Correspondence: recently in recommended drug for black fungus i.e., Liposomal Amphotericin B. Although,
Faisal Farooque, Department of Biochemistry,
their development and application are remaining the challenge due to costly and tedious
Faculty of Life Sciences, Aligarh Muslim University, processes involved in their production and development. Therefore, further research and
Aligarh, India-202002. development are required to perform to overcomes these challenges.
ORCID ID: https://orcid.org/0000-0001-9069-2335 Keywords: Liposome, characterization, amphiphatic, controlled release, phospholipids

INTRODUCTION The ongoing researches focus more on the growth of long


circulating stealth liposomes and multi-functional liposomes
In comparison to conventional drugs, the primary purpose of with advanced in vitro properties.3
a targeted drug delivery is to efficiently distribute a drug
directly to the site of action to achieve better efficacy and to Liposomes were discovered 54 years ago by British
reduce adverse effects. Amongst numerous carrier system, hematologist Dr. Alec D Bangham that possesses the multi-
liposomes have generated an excellent interest as a result of faceted tool in medicine, biology and biochemistry
their versatility. Liposomes are a desirable delivery method nowadays. In the year 1960 liposome were used as a
because of their adaptable physicochemical and biophysical transporter in its aqueous compartment to transport a wide
characteristics, which allow for simple modification to meet range of compounds. It is possible to develop and process
a variety of delivery needs. Liposomes are bilayered vesicles liposomes varying in size, structure, charge and lamellarity.
that are concentric in shape, having a diameter of 0.01–5.0 At present anti-tumor medications and antifungal agents in
μm as it may be made from cholesterols, glycolipids, non- liposomal forms are commercially available.
harmful surfactants, long chains of fatty acids, sphingolipids  Classification of Liposomes4- 6
and even membrane protein.1 Liposomes are vesicular
structures that develop when phospholipids are spread in The Liposomes classification are based on-
water and have an inner aqueous phase enclosed by
i. Structure
phospholipid bilayer membranes. The liquid interior was
encased in a sphere-like container, which contained ii. Preparation Process
substances like peptides & protein, antibiotic, enzymes,
hormones, antimycotic & antitumor agents and even iii. Constituent and its Application
plasmids.2 Liposomes mostly consist of biocompatible and iv. Conventional liposome
biodegradable materials capable of encapsulating both
hydrophobic and hydrophilic molecules on one platform. v. Liposome specialty

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1) Based on Structure
Table 1: Diameter Size and number of lipid layers of different vesicles
Vesicle type Abbreviation Diameter Size No. of Lipid Layers
Unilamellar vesicle UV All size ranges One
Small Unilamellar vesicle SUV 20-100 nm One
Medium Unilamellar vesicle MUV More than 100 nm One
Large Unilamellar vesicle LUV More than 100 nm One
Giant Unilamellar vesicle GUV More than 1.0 μm One
Oligolamellar vesicle OLV 0.1-1.0 μm Approx. 0.5
Multilamellar vesicle MLV More than 0.5 μm 5-25
Multi vesicular vesicle MV More than 1.0 μm Multi compartmental structure

2) Based on Method of Preparation


Table 2: Different methods of preparation and the vesicles developed by those methods
Preparation Method Vesicle Type
Lamellar vesicle of a single or oligo formed by reverse phase evaporation REV
Multi lamellar vesicles formed by the method of reverse phase evaporation MLV-REV
Stable pluri lamellar vesicle SPLV
Frozen and thawed multi lamellar vesicle FATMLV
Vesicle prepared by extrusion technique VET
Dehydration-Rehydration method DRV

3) Based on Composition and Application


Table 3: Different Liposome with their Compositions
Type of Liposome Abbreviation Composition
Conventional CL Neutral or negatively charge phospholipids and cholesterol
Fusogenic RSVE Reconstituted sendai virus envelops
pH sensitive - Phospholipids such as DOPE or PER with either OA or CHEMS
Cationic - Cationic lipid with DOPE
Long circulatory LCL Neutral high temp, cholesterol, and 5-10% PEG, DSP
Immuno IL CL or LCL with monoclonal antibody linked or sequences of recognition

4) Based upon Conventional Liposome vi. Antibody directed


i. Normalize Mixtures of Natural Lecithin (PC) There are several pathways in and outside the body by
which liposomes can operate, which are as follows7:-
ii. Glycolipid-loaded liposome
i. Liposome binds to the plasma membrane and seems to
iii. Synthetic phospholipids with the same chain as natural
fuse with them, allowing the substance to be released
phospholipids
into the cell.
5) Based upon Specialty Liposome
ii. When they are absorbed by the cell, their
i. Carbohydrate coated phospholipids are linked further into plasma
membrane, allowing the medication to be released
ii. Bipolar fatty acid imprisoned inside.
iii. Lipoprotein coated iii. The liposomes are taken up in the case of phagocyte
iv. Methyl/ Methylene x- linked cells, organelles called lysosomes function on the
phospholipid walls and the active pharmaceutical
v. Multiple encapsulated ingredients are released.

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STRUCTURAL COMPONENTS OF LIPOSOMES chains creating defects in the cell membrane like packaging.
During packaging those liposome’s leak the encapsulated
The major constituents of liposome includes drug. One or two bilayer stabilizers are also used in most
 Phospholipids liposome formulation in order to avoid such leakage. The
additives more widely used are cholesterol and alpha-
 Cholesterol tocopherol. Liposome encapsulation quality varies with
variations in the composition of the phospholipid bilayer.
Phospholipids
Cholesterol is indeed an absolutely vital component of
The fundamental building blocks of bio membranes are natural lipid bilayers and its presence in bilayer liposomes
phospholipids. Phosphatidylcholine (PC) is perhaps the most induces drastic alteration in their characteristics.
often utilised phospholipid in liposome composition.8 Cholesterol by itself doesn't develop bilayer complexes, but
Phosphatidylcholines derived from natural origins or can be integrated into high concentrations of phospholipid
synthesized using semi-synthetic and synthetic techniques. membranes. Rigidity is enhanced due to compact stacking of
In terms of bilayer sheet orientation in relation to micellar the bilayers, and permeability of water-soluble molecules is
compositions, phosphatidylcholines vary significantly from reduced. By reducing bilayer permeability, cholesterol
other phospholipids. The preparation of liposomes is based enhances the durability of hydrophilic drugs. Cholesterol
on a number of natural and semi-synthetic phospholipids. reduces the fluidity above the phase transition temperature
(Tc) to make the bilayer more ordered.11 The tricyclic ring is
The molecules of phosphatidylcholine are not miscible in wedged among the first few carbons of the fatty acyl chains,
water. They develop a planar bilayer configuration in and the hydroxyl group is exposed to the liquid phase, the
aqueous environments to decrease undesirable interactions cholesterol molecule fits in with the phospholipid molecules
between the bulk aqueous environments as well as in non- and orients itself among them. At very significant
esterified fatty acid. The sheets are then folded into enclosed concentrations, cholesterol to phospholipids ratios of up to
capsules.9,10 1:1 or even 2:1 can be incorporated into the cellular
Cholesterol membrane.12 Albumin, macroglobulin, and m-transferrin are
blood proteins that interact more easily and frequently with
Typically, liposomes prepared by using only phospholipids cholesterol-free liposomes enabling the vesicle to become
are not sufficiently rigid primarily because of low phase unstable as a result its usage as a therapeutic delivery
transition temperature and/or unsaturation in the fatty alkyl method has declined.

The figure is showing that the drugs can either be incorporated inside the aqueous space (hydrophilic drugs) or inside the
phospholipid bilayer (hydrophobic drugs) of liposomes for the targeted drug delivery.

THE FORMATION OF VESICLES METHODS OF PREPARATION


To synthesize lipid vesicles, thin layer lipid films must be Basically, all the liposome preparation strategies have four
properly hydrated and inflated. During agitation, large MLVs basic steps.
are formed when hydrated lipid sheets split, stopping water
I. Drying down lipid from organic solvent
from interfering with the bilayer's hydrocarbon core at the
margins. After the particles are produced, they have been II. Dispersing the lipid in aqueous media
sonicated or extruded to decrease their size.11
III. The purification of the resulting liposome
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IV. Examination of final products high velocity at the right angle together. Micro emulsion
can be developed for biological applications by regulating
The three distinct liposome preparation methods are as
rotation speeds from 20 to 200.18
follows:
 Sonication
1) Passive loading technique
This technique decreases the size of the vesicles and
a) Mechanical Dispersion
provides energy to lipid mixture. This can be
i. Lipid film hydration method (Hand shaking/Non-hand accomplished by irradiating the MLV with ultrasonic
shaking) waves. Sonication can be done in two different ways (i)
using bath sonicator (ii) using probe sonicator. The probe
ii. Micro emulsification sonicator is often used for suspensions that demand a lot
iii. Sonication of energy in a little amount of volume.19-21. For
substantial volumes of dilute lipids, the bath sonicator is
iv. French pressure cell used. The primary disadvantages of this technique are its
v. Membrane extrusion poor internal encapsulation efficacy, phospholipid
disintegration, elimination of particularly huge
vi. Dried reconstituted vesicles molecules, metal impurities from the probe tip, and the
coexistence of MLV and SUV.22,23
vii. Freeze-thawed liposomes
 French Pressure Cell Method
b) Solvent dispersion
MLV is extruded via a tiny hole at 20,000 pressure and 4°C
i. Ethanol injection method
during the process. In comparison to sonication
ii. Ether injection method techniques, the method offers numerous advantages. The
approach is simple, quick, and repeatable, yet it entails
iii. Double emulsion carrying hazardous materials with care. Liposomes
iv. Reverse-Phase evaporation produced as a result are considerably bigger than those
produced by sonicated SUVs. The drawbacks comprise
c) Detergent Removal difficulties in attaining temperature and the working
i. Detergent removal from mixed micelles vesicle by volumes are comparatively smaller (a maximum of 50
Dialysis dilution mL).24

2) Active loading technique  Membrane extrusion

a) Proliposome lyophilization A heterogeneous liposomal suspension is processed via a


polymer sieve with a web like fabrication that develops a
1. Technique of passive loading 13- 15 tortuous-path capillary pore, an interconnected network
having not less than 100 micron thick membrane. The
a) Mechanical dispersion
liposomes that were treated had a small distribution of size
 Lipid Hydration Method and a chosen mean size of less than about 0.4 microns.25 Both
LUVs and MLVs can be processed using this approach.
This is perhaps the most well-known and widely utilized
approach to make MLVs. The round bottomed flask can be  Dried reconstituted vesicles
utilised for its formulation. The procedure entails forming a
In this approach, liposomes are combined with lyophilized
thin coating by dehydrating the lipophilic mixture and on
protein or introduced to an aqueous solution containing
hydrating the membrane by introducing an aqueous buffer
pharmaceutical and after that dehydrated.26
as well as thoroughly mixed the dispersion. The hydration
stage is performed at a temperature higher than the gel–  Freeze-Thaw Method
liquid-crystalline (Lβ→Lα) transition temperatures of the
lipid or just above the transition temperature of the lipid In this procedure, SUVs are rapidly frozen then gradually
mixture's maximal melting part. The pharmaceuticals thawed. Aggregated compounds are dispersed to LUV by
somehow been enclosed are introduced to an aqueous buffer sonication. The formation of unilamellar vesicles in the
or into an organic solvent comprising lipids solvents freezing and thawing processes is a result of SUV17. This
depending on their solubilites. The method's drawbacks form of fusion is highly hindered by enhancing the medium's
include low internal volume, lower efficiency of ionic strength and by enhancing the amount of
encapsulation and differing size. Diethyl ether overcomes the phospholipids. This technique was used to achieve
poor encapsulation ability of lipids by hydrating them in the entrapment efficiency of about 20 to 30%.27
presence of immiscible organic solvents like petroleum b) Solvent dispersion
ether. After that, sonication is used to emulsify the mixture.
By removing organic layer by passing nitrogen, MLVs are  Ethanol Injection Method
developed.16 This is simple technique. In this approach, an ethanol lipid
 Micro emulsification solution is quickly incorporated directly through a fine
needle into an excess of saline or other aqueous media.28 In
This technique is used in commercial scales to prepare small water, ethanol is dissolved and phospholipid molecules are
lipid vesicles. For the preparation of tiny vesicles uniformly distributed through the medium. The main
somewhat from concentrated lipid suspension, disadvantage of this approach is that the particles can have a
an apparatus called a micro fluidizer is used. As a heterogeneous particles size (30-110 nm). Another major
suspension of large MLVs, the lipids should be taken into downside is that it is difficult to remove all ethanol, which
the fluidizer. This machine pumps the fluid into a 5μm may lead to the formation of azeotrope with water.22
panel at very high pressure.17 Then a long micro channel
is forced, which drives two fluid streams colliding at very

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 Double emulsification and reproducible. The typical methods of sizing liposomes


are sequential extrusion, gel chromatography and
In this approach, a primary emulsion is produced by mixing
sonification.40
the therapeutics in an aqueous phase (w1), which is further
emulsified to produce a primary w1/o emulsion in an organic However, these methods have the following disadvantages in
polymer solvent. The w1/o/w2 double emulsion is created the long run:
by combining the foremost emulsion with an emulsifier-
1. It's difficult to keep oxygen out, which leads to a per
containing aqueous solution (w2).23 In the aqueous
oxidation process.
continuous stage, when the solvent is removed,
microspheres are left behind that are further separated by 2. Metal particles are shed by titanium probes, resulting in
filtering/centrifuging. toxicity.
 Reverse-phase evaporation 3. They will develop aerosols that restrict them from the
use of such agents.
In an Erlenmeyer bulb the lipid mixture is taken and the
solvent is removed at decreased pressure using a rotary These issues are primarily due to the probe's sonication, but
evaporator. The lipids are disintegrated in the organic phase using the bath sonication will eliminate these problems.
once the nitrogen has been removed.29 This phase will see
the development of reverse phase vesicles. The standard CHARACTERIZATION OF LIPOSOMES 41- 46
solvents used are isopropyl ether and diethyl ether. Just after
The liposome must be characterized after preparation and
the lipids have been re-dispersed among this phase, an
before use in immunoassays. The assessment may be
aqueous phase containing the pharmaceutical to be
categorized into three broad categories: physical, chemical
encapsulated is added. The all-aqueous systems are
and biological methods. The physical methods require
sonicated till the combination generates a distinct one-phase
different criteria, such as shape, size, surface features,
dispersion and the system is preserved under nitrogen
lamellarity phase behaviors and drug release profile.
pressure at all times. The combination is further transferred
to arotovap and organic solvent removal is carried out until a Chemical characterization refers to research that have
gel is developed followed by non-encapsulated substance determined the purity and efficiency of different liposomal
removal.29,30. Reverse-phase evaporation vesicles are the components.
resulting liposomes that emerge from this process. The
method's major benefit is its extremely high encapsulation Biological characterization aids in the analysis of a
efficiency.31,32 formulation's effectiveness and viability for in vivo
pharmacological intervention.
c) Detergent removal
1. Visual Appearance
At their optimum micellar concentrations, detergents
solubilize lipids. The micelles became more enriched in The appearance of the liposomal suspension can vary from
phospholipids when the detergent was eliminated using transparent to milky depending on the particle size and
dialysis and eventually fused to create LUVs.14 High composition. If the turbidity has a bluish shade, the
reproducibility as well as the development of homogenous samples are homogeneous; non-liposomal dispersion
liposome populations are two of the positive effects of the occurs in a flat, grey color and is most usually a
detergent dialysis approach. The primary downside of the distributed inverse hexagonal phase or dispersed micro
technique is that detergent residues are retained.15 crystallites. In addition to contamination of larger
particles, an optical microscope can detect liposomes
2. Active loading technique larger than 0.3 μm.
 Proliposome 2. Determination of Liposomal Size
In this technique lipid and drug were coated onto a soluble The size distribution is of primary importance when
carrier to develop free flowing granular component in pro- liposomes are intended for inhalation or parenteral
liposome which when hydrated forms an isotonic liposomal administration, as it regulates the in vivo fate of liposomes
solution.33 The pro-liposome strategic approach will offer an along with the encapsulated drug molecules. Liposome is
incentive for large-scale, cost-effective manufacturing of usually measured by dynamic light scattering. For this
liposomes incorporating lipophilic drugs in particular.34 method, liposomes with a relatively homogeneous
distribution of size are reliable. Gel exclusion
 Lyophilization
chromatography is a direct way of detecting a completely
The separation of water from substances at highly reduced hydrodynamic radius. In the 30-300nm size range,
pressure in the frozen state is termed cryodesiccation (freeze sephacryl-S100 will separate liposomes. SUVs can be isolated
drying). The technique is extensively employed to dry from micelles by sepharose columns -4B and -2B.
thermolabile materials that can be ruined by heat-drying.
3. Determination of lamellarity
With regard to liposomal stability, this procedure serves as
an important tool for resolving long-term stability issues. The determination of lamellarity is important in defining the
During the freeze-drying and reconstitution process, leakage liposome structure and it’s in vivo efficiency. The efficacy of
of trapped materials can take place.35,36 encapsulation and the kinetics of drug release are greatly
affected by the amount of lipid bilayers in the liposome.
SIZING OF LIPOSOME Lamellarity influences the uptake of liposomes and
The size of the liposome seems to have a significant impact intercellular fate. The Liposomal lamellarity varies greatly
on their fate or the purpose for which it may be employed. depending on lipid selection and methods of preparation.
The functional viability and uniformity of phospholipids Electron microscopy or spectroscopic techniques may
bilayer are required for therapeutic uses of liposomes.37- 39. calculate the lamellarity of liposomes. The NMR liposome
Therefore, with particle size distribution within a certain size spectrum is most commonly reported with and without the
range, the liposome processing process must be predictable addition of a paramagnetic agent that changes or bleaches

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the signal of the observed nuclei detected on the outer III. Low oxygen demand must be maintained (Nitrogen
liposome surface. purging)
4. Liposome Stability IV. Use of antioxidant or metal chelators
Stability is an essential factor to consider when using V. Formulating at neutral pH
liposomal drug delivery systems. The processing system and
VI. Usage of lyo-protectant in freeze-drying conditions
storage conditions have an impact on the physical stability
and chemical purity of a drug molecule. The liposomal APPLICATION OF LIPOSOME
stability of the drug molecules regulates their therapeutic
function. Size, size distribution, composition and drug Liposome research has progressed dramatically in the
retention are correlated with the physical integrity of previous 30 years. A large variety of liposome’s of variable
liposomes, whereas Chemical equilibrium struggles with sizes, phospholipid constituents, cholesterol constituents
phospholipid oxidation and hydrolysis, as well as drug and surface morphologies can now be developed suitable for
degradation. A safe liposomal medicinal product has a a wide range of applications.50
qualified physical, chemical and microbial stability that
The liver and spleen may be targeted using the liposome
guarantees the integrity of the products during its storage
carrier, and tomography can easily differentiate between
time. Therefore, a given stability study protocol emphasizes
malignant and non - malignant tissue. Liposome has a great
its significance in deciding the products physical and
use in the case of the transdermal drug delivery system. In
chemical integrity having a well-established methods for
the treatment of tumor cells the liposomal drug delivery
development, characterization, effectiveness and stability
mechanism contributes to a decrease in the toxic effect and
testing.
increases drug efficacy. Liposomes are targeted at the region
5. Entrapped Volume of operation by binding a fragment of amino acid to
particular cell receptors.51
This is an important parameter that regulates vesicle
morphology. The entrapped liposome volume (in μL/mg DNA vaccination and increased gene therapy success is only
phospholipids) can also be deduced from measurements of a couple of the latest liposomal treatment applications. Many
the cumulative amount of solute trapped within liposomes, sorts of drug administration implementations have been
ensuring that the concentration of solute within liposomes in suggested for the liposomal drug delivery, some of which are
the aqueous medium is the same after isolation from the mentioned below:
untrapped material. During the drying down process, water
I. Enhance drug solubilisation (Cyclosporins, Minoxidil,
from the inner compartment may be lost in two phases of
Amphotericin-B and Paclitaxels)
preparation to eliminate organic solvent.
II. Drug molecules that are sensitive are protected
This can be calculated by a given formula
(Cytosine arabinosa, Ribozymes, DNA, Anti-sense oligo-
nucleotides and RNA)
III. Enhance intracellular uptake (Anti-microbial, Anti-
tumor and anti-viral drugs)
6. Surface Charge
IV. Modification in pharmacokinetics and bio-
The nature and density of charge on the liposome surface distribution(prolonged or sustained released drugs
will regulate the lipid-cell interaction. Liposomes are with short circulatory half-life)
typically prepared by means of charge
A. Liposome for Respiratory Drug Delivery System52
imparting/constituting lipids and hence the charge on the
surface of the vesicle is examined. In general, two procedures Liposomes are typically used in many forms of respiratory
are employed to analyse the charge: free flow illnesses. It is possible to formulate liposomal aerosols to
electrophoresis and zeta potential testing. develop prolonged release, avoid local inflammation,
minimize side effects and improve stability throughout the
STABILIZATION OF LIPOSOME vast aqueous core.
Liposome safety should conform with the same quality as Numerous injectable liposome-based drugs, including
conventional drug formulations. The durability of any ambisome, Fungisome and Myocet, are now available in the
pharmaceutical substance is the potential of the delivery market. To be successful, the delivery mechanism of
mechanism to stay within specified or predefined limits over liposomal drugs to the lungs depends on lipid composition,
a fixed period in the prescribed formulation. Chemical charge, size, drug & lipid ratio and delivery techniques. The
stabilization necessitates the avoidance of ester bond emerging application of liposomes for DNA transmission to
hydrolysis in phospholipid bilayers as well as the oxidation the lungs indicating that a better knowledge of their usage in
of unsaturated lipid chain sites. Physical instability or leaking macromolecules administration by inhalation is now
of encapsulated drug from bilayers leads to vesicle developing. All of this new expertise can be used to improve
aggregation as a result of chemical instability.47 liposome-based protein formulations. The liquid or dried
Efficient formulation and lyophilization are methods that can form is utilized for liposome inhalation and the
be taken to improve liposomal stability. Generally, liposomes pharmaceutical is released during nebulization. Milling or
can cause stability problems during the storage period. sprays drying have been used to develop drug powder
Certain factors need typically be addressed in order to liposomes.
ensure effective formulation of a stable liposomal drug B. Liposome in Eye Disorders
component: 48,49
Liposomes have long been utilised to treat both the anterior
I. Processing with fresh, purified lipids and solvents and posterior regions of the eye. Dryness, keratitis,
II. Elevated temperature avoidance and excessive shear proliferative vitreoretinopathy, endopthelmitis, and corneal
forces graft rejection are all eye diseases. In developing nations,

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retinal abnormalities constitute the single biggest cause of permeability of the membrane. Because of its non-specificity
blindness. Liposomes are employed as a genetic transfection and affinity to cholesterol in mammalian cells this substance
vector and a carrier for monoclonal antibodies. In the is hazardous. The first liposome formulation of Amphotericin
therapy of targeted tumors and neovascular artery occlusion, B has recently been performed in all clinical tests and is now
angiography, retinal and choroidal blood vessel stasis, recent commercialized fortreating various fungal diseases such as
treatment strategies such as the application of heat-activated Mucormycosis (Black Fungus), aspergillosis, blastomycosis,
liposomes in focused lasers, as well as heat-induced release candidiasis, coccidioidomycosis, and cryptococcosis.
of liposomal therapeutics and dyes for targeted delivery. To Liposomal Amphotericin B decreases renal and general
far, two patent medicines have received approval for toxicity at the usual dosage by passively targeting the liver
liposomal drug formulations, and many more are undergoing and spleen, but renal toxicity usually happens whenever
scientific testing. 'Verteporfin' is a commercially endorsed drug is delivered at a high dose due to liver and spleen
liposomal medication for ocular usage. The relevance of the macrophage saturation. By coating the vesicle using o-
liposome will be expanded in the future to include the stearoyl amylopectin, polyoxyl ethylene, or mono-
therapeutic, diagnostic, and research aspects of sialogangliocyte liposomes can also be specifically targeted
ophthalmology.53 to the lungs. The encapsulation in the lung-targeted liposome
of ant tuberculous agents such as isoniazid and rifampicin
C. Liposome as Vaccine Adjuvant 54
modulates toxicity and increases the effectiveness of these
Liposomes are a well-known immune adjuvant that enhances products.59 Varieties of formulations of amphotericin have
both cell-mediated and non-cell-mediated immunity. been approved in many clinical trials and are now being sold
Liposomal immune adjuvants work by releasing in numerous European countries.60
encapsulated antigen slowly and passively into the localized
F. Liposome in Tumor Cell Therapy
lymph node after intramuscular injection. Accumulation of
liposomes into lymphoid is accomplished by targeting Anti-cancer medicines have serious hazardous side effects
liposomes with the aid of phosphotidyl serine. It is possible when taken for a long time. The liposomal treatment for
to prepare a liposomal vaccine by immunizing bacteria, tumor cell targeting has enhanced the field of tumor
soluble antigen and deoxyribonucleic acid cytokinesis with treatment by reducing side effects to a minimum. Although
liposomes. However, it induces immunological reaction to the tiny and stable liposome are supposed to be passively
antigenic protein expression. Antigens will further combine targeted to various tumors although they can circulate for
with the liposomal membrane in a covalent manner. prolonged periods of time and can additionally vasate in
Liposomal vaccines can be kept for around 12 months in a tissues with increased vascular permeability.61,62. The intake
refrigerated state.55 of liposome macrophages by the liver and spleen has
impeded liposome growth as a drug delivery for more than
D. Liposomes for Brain Targeting
20 years. Many herbal anticancer medications have now
Liposomes have lately gained popularity as a brain drug been incorporated into liposome to provide improved
delivery mechanism due to their biocompatibility and targeting with increased bioavailability.63
biodegradability.56 Liposomes with small (100 nm) or even
big diameters diffuse freely across the Blood Brain Barrier
ADVANCEMENTS IN LIPOSOMES
(BBB). SUVs linked to cognitive drug carriers, on the other  Ethosomes: They are effective in delivering soya
hand can be carried across the BBB by receptor-mediated or phosphatidylcholine and 30% ethanol to the skin.
absorptive-mediated transcytosis. Absorptive mediated
endocytosis of cationic liposomes occurs in cells, however it  Immuno liposomes: They were modified with
has yet to be proven that absorptive induced transcytosis antibodies.
occurs across the BBB .The mannose-coated liposomes reach  Niosomes: They are small unilamellar vesicles composed
the brain and help in drug transport across the BBB. When of surfactants that are non-ionic.64
systemically administered, the Leu-enkephalin,
mefenkephalinkyoforphin and neutropeptides do not  Stealth liposomes: These are new types of liposome
typically penetrate the blood-brain barrier. Due to the designed to enhance stability and extend their half-life in
versatility of this approach, the anti-depressant amitriptyline circulation. Coating of liposomes should be done by poly
usually penetrates the BBB. Nanoparticles (NP) have been ethylene glycol (PEG) for preparing these liposomes.8
developed from various stabilizers. The amount of
Liposome’s in biomedical research applications: An
amitriptyline was observed to be substantially increased in
Experiment
the brain when the drug was adsorbed to the NP and
wrapped or particle remained stable with polyoxyethylene The use of liposomes in healthcare has the potential to
20 sorbitan trioleate.57 provide innovative and effective therapies for a variety of
E. Liposome as Anti-Infective Agents pathological diseases. At the trial in vitro and in vivo stages
there appears to be a significant increase in lipid–based
The intracellular pathogen such as protozoa, bacteria and therapeutic carrier research. Liposomes are being used to
fungi reside in the liver and spleen and thus the therapeutic transport a broad variety of therapeutic and diagnostic
substances can be administered to such organs using components including therapeutic molecules, bioactive
liposomes as the transport system to remove these agents and gene therapy.65 Alterations in lipid content,
pathogen.58 It is possible to treat diseases such as charge and the inclusion of surface coatings and ligands are
leishmaniasis, histoplasmosis, candidiasis, erythrococosis, all being looked into to increase effectiveness, reduce RES
aspergelosis, gerardiasis, tuberculosis and malaria by clearance, and limit toxicity.65,66
integrating and targeting the medication with the liposomal
For a number of biological applications, active targeting
carrier.
methods involving the conjugation of targeting ligands to the
Amphotericin B, a polyene antibiotic is associated with surface of liposomes have been widely explored at the early
significant kidney damage when used to treat systemic stage of the research especially following parenteral
fungal infection. Amphotericin B acts by binding to sterol in injection.67- 69. Targeting ligands are utilised to enhance the
the membrane of susceptible fungi, thereby enhancing the selectivity of encapsulated cargo delivery to and retention in
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