Liposomes Notes NT
Liposomes Notes NT
2021; 11(5-S):149-158
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
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.
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
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,
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
ISSN: 2250-1177 [155] CODEN (USA): JDDTAO
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