AN OVERVIEW ON LIPOSOMES: A NOVEL DRUG DELIVERY SYSTEM. RPA1516256015.pdf · an overview on...

79 | P a g e International Standard Serial Number (ISSN): 2319-8141

Full Text Available On www.ijupbs.com

International Journal of Universal Pharmacy and Bio Sciences 4(6): November-December 2015

INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND BIO SCIENCES

IMPACT FACTOR 2.093*** ICV 5.13*** Pharmaceutical Sciences REVIEW ARTICLE …………!!!

AN OVERVIEW ON LIPOSOMES: A NOVEL DRUG DELIVERY SYSTEM

Shewale Lankesh1*

.Gondkar S.B1, Saudagar R.B

2.

1*Department of Pharmaceutics, R.G. Sapkal college of pharmacy, Anjaneri, Nashik-422213,

Maharashtra, India. 1*

Department of Pharmaceutics, R.G. Sapkal college of pharmacy, Anjaneri, Nashik-422213,

Maharashtra, India. 2*

Department of Pharmaceutical Chemistry, R.G. Sapkal college of pharmacy, Anjaneri, Nashik-

422213, Maharashtra, India.

KEYWORDS:

Liposomes,

Phospholipids,

Classification,

Limitation,Glycolipids,

Structural Components.

For Correspondence:

Shewale Lankesh*

Address:

Department of

Pharmaceutics, R.G.

Sapkal college of

pharmacy, Anjaneri,

Nashik-422213,

Maharashtra, India.

ABSTRACT

Liposomes represent an important class of carrier vehicles other than the

polymers for drug delivery. This review provides an introduction and

general review of liposomes with emphasis on their classification, their

constituent materials, their preparation and characterization, and their

stability and biodistribution in the body. The main objective of drug

delivery system is to deliver a drug effectively, specifically to site of

action and to achive greater efficacy and to minimize the toxic effect

compared to conventional drug. Among various carrier systems, liposomes

have generated a great interest because of their versatility. Liposomes are

vesicular concentric bilayered structure, which are biocompatible,

biodegradable and nonimmunogenic. They can control the delivery of drug

by targeting the drug to the site of action or by site avoidance drug

delivery or by prolonged circulation of drug. After the formulation, the

evaluation of liposomes are checked by using physical parameters,

chemical parameters, and biologically for the establish the purity and

potency of various lipophilic constituents and establish the safety and

suitability of formulation for therapeutic application.



INTRODUCTION:

Liposomes were first described by British haematologist Dr Alec D Bhangham in 1961

(published 1964), at Babraham Institute, in Cambridge. They were discovered when

Bangham and R.W. Horne were testing the institute’s new electron microscope by adding

negative stain to dry phospholipids. Liposomes are defined as structure consisting of one or

more concentric spheres of lipid bilayers seprated by water or aqueous buffer compartment or

Liposomes are simple microscopic vesicles in which an aqueous volume is entirely enclosed

by a membrane composed of lipid bilayers. The name liposome is derived from two Greek

words: 'Lipos' meaning fat and 'Soma' meaning body. A liposome can be formed at a variety

of sizes as unillamellar or multi-lamellar construction, and its name relates to its structural

building blocks, phospholipids, and not to its size. A liposome does not necessarily have

lipophobic contents, such as water, although it usually does. Liposomes are artificially

prepared vesicles made of lipid bilayer. Liposomes can be filled with drugs, and used to

deliver drugs for cancer and other diseases. Liposomes can be prepared by disrupting

biological membranes, for example by sonication. Liposomes are micro particulate or

colloidal carriers, usually 0.05- 5.0 μm in diameter which form spontaneously when certain

lipid are hydrated in aqueous media. Liposomes are composed of relatively biocompatible

and biodegradable material, and they consist of an aqueous volume entrapped by one or more

bilayer of natural and/or synthetic lipids. Drug with widely varying lipophilicities can be

encapsulated in liposomes, either in the phospholipids bilayer, in the entrapped aqueous

volume or at the bilayer interface. The delivery of drugs onto the skin is recognized as an

effective means of therapy for local dermatologic diseases. Liposome is acceptable and

superior carrier and has ability to encapsulate hydrophilic and lipophilic drugs and protect

them from degradation. Topical drug administration is a localized drug delivery system any

where in the body through ophthalmic, rectal, vaginal and skin as topical routs. Skin is one of

the most readily accessible organs on human body for topical administration and is main

route of topical drug delivery system. Topical application of liposome vesicles has many

advantages over the conventional dosage forms. However major limitation of using

liposomes topically is the liquid nature of preparation. They can be overcome by their

incorporation in adequate vehicles where original structure of vesicles is preserved. It has

already been shown that liposomes are fairly compatible with gels made from polymers

derived from cross linked polyacrylic acid, such as carbopol resins.



Fig.1.Structure of liposome

ADVANTAGES OF LIPOSOMES[1,2,7]

1. Provide controlled drug delivery

2. Biodegradable, biocompatible,flexible

3. Non ionic

4. Can carry both water and lipid soluble drugs

5. Drug can be stabilized from oxidation

6. Improve protein stabilization

7. Provide sustain release action

8. Can be administered through various routes

9. Therapeutic index of drug is increased

10. Can act as reservoir of drug

11. Direct interaction of the drug with cell

12. Targeted drug delivery or site specific drug delivery.



DISADVANTAGES OF LIPOSOMES[1,2,7]

1. Less stability

2. Low solubility

3. Short half life

4. Phospho lipid undergoes oxidation, hydrolysis

5. Leakage and infusion

6. High production cost

7. Allergic reactions may occurs to liposomal constituents

8. Quick uptake by cells of R.E.S

9. Problem to targeting to various tissue due to their large size.

CLASSIFICATION OF LIPOSOMES [1,2,7]

Table no: 1. Based On Structure Parameter

TYPE-1 SPECIFICATION

BASED ON STRUCTURE PARAMETER

MLV

OLV

UV

SUV

MUV

LUV

GUV

MV

Multilamellar large vesicle->0.5μm

Oligolamellar vesicle-0.1-0mm

Unilamellarvesicle (all range size)

Small sized unilamellar vesicle

Medium sized unilamellar vesicle

Large unilamellar vesicle-> 100mm

Giant unilamellar vesicle- >1mm

Multivesicular vesicle >1mm



Table no:2Based On Liposomes Preparation


BASED ON LIPOSOMES

PREPARATION

REV

MLV-REV

SPLV

FATMLV

VET

DRV

Single or oligolamellar vesicle made by

reverse phase evaporation method

Multilamellar vesicle made by reverse

phase evaporation method

Stable plurilamellar vesicle

Frozen and thawed MLV

Vesicle prepared by extrutiontechnique

Dehydration rehydration method

Table no:3Based Upon Composition And Application


BASED UPON COMPOSITION AND

APPLICATION

Conventional liposome

Cationic liposome

Long circulatory liposome

pH sensitive liposome

Immuno liposome

Neutral or negatively charged Phospholipid

Cationic lipid

Neutral high Transition temperature

liposme

Phospholipid like Phosphatidyl

ethanolamine

Long circulatory liposome with attached

monoclonal antibody

STRUCTURAL COMPONENT OF LIOPOSOMES[3,4,5]

A. Phospholipids

Glycerol containing phospholipids are most common used component of liposome

formulation and represent greater than 50% of weight of lipid in biological membranes.

These are derived from Phosphatidic acid. The back bone of the molecule is glycerol moiety.

Examples of phospholipids are

- Phosphatidyl choline (Lecithin) – PC

- Phosphatidyl ethanolamine (cephalic) – PE

B. Sphingolipids

Backbone is sphingosine or a related base. These are important constituents of plant and

animal cells. This contain 3 characteristic building blocks



- A head group that can vary from simple alcohols such as choline to very complex

carbohydrates.

- Sphingolipids – Sphingomyelin. Glycosphingolipids.

- Gangliosides – found on grey matter, used as amin or component for liposome production.

C. Sterols

Cholesterol & its derivatives are often included in liposomes for

- decreasing the fluidity or micro viscocity of the bilayer

- reducing the permeability of the membrane to water soluble molecules

- Stabilizing the membrane in the presence of biological fluids such as plasma.( This effect

used in formulation of i.v. liposomes)

Liposomes without cholesterol are known to interact rapidly with plasma protein such as

albumin, transferring, and macroglobulin. These proteins tend to extract bulk phospholipids

from liposomes, thereby depleting the outer monolayer of the vesicles leading to physical

instability. Cholesterol appears to substantially reduce this type of interaction. Cholesterol

has been called the mortar of bilayers, because by virtue of its molecular shape and solubility

properties, it fills in empty spaces among the Phospholipids molecules, anchoring them more

strongly into the structure. The OH group at 3rd

position provides small Polar head group and

the hydrocarbon chain at C17 becomes non polar end by these molecules, the cholesterol

intercalates in the bilayers.

D. Synthetic phospholipids

Saturated phospholipids are

1 Dipalmitoylphosphatidyl choline (DPPC)

2 Distearoylphosphatidyl choline (DSPC)

3 Dipalmitoylphosphatidyl ethanolamine (DPPE)

4 Dipalmitoylphosphatidyl serine (DPPS)

5 Dipalmitoylphosphatidicacid (DPPA)

6 Dipalmitoylphosphatidyl glycerol (DPPG

Unsaturated phospholipids

1. Dioleoylphosphatidyl choline (DOPC)

2. Dioleoylphosphatidyl glycerol (DOPG)

E. Polymeric materials

Synthetic phospholipids with diactylenic group in the hydrocarbon chain polymerizes when

exposed to U.V, leading to formation of polymerized liposomes having significantly higher



permeability barriers to entrapped aqueous drugs. E.g.: for other Polymerisable lipids are –

lipids containing conjugated diene, Methacrylate etc. Also several

Polymerisablesurfactantsare also synthesized.

F. Polymer bearing lipids

Stability of repulsive interactions with macromolecules is governed mostly by repulsive

electrostatic forces. This repulsion can be induced by coating liposome surfaces with charged

polymers. Non ionic and water compatible polymers like polyethylene oxide, polyvinyl

alcohol, and Polyoxazolidines confers higher solubility. But adsorption of such copolymers

containing hydrophilic segments with hydrophobic part leads to liposome leakage, so best

results can be achieved by covalently attaching polymers to phospholipids.

E.g.: DiacylPhosphatidyl ethanolamine with PEGpolymer linked via a carbon at or succinate

bond.

G. Cationic lipids

E.g.: DODAB/C – Dioctadecyl dimethyl ammonium bromide or chloride

DOTAP – Dioleoyl propyl trimethyl ammonium chloride this is an analogue of DOTAP and

various others including various analogues of DOTMA and cationic derivatives of

cholesterol.

METHOD OF PREPARATION OF LIPOSOMES[8,9,10]

The following methods are used for the preparation of liposomes:

· Passive loading techniques

· Active loading technique.

Passive loading techniques include three different methods:

1 Mechanical dispersion method.

2 Solvent dispersion method.

3 Detergent removal method (removal of non encapsulated material).

1. Mechanical dispersion method

The following are types of mechanical dispersion methods:

· Sonication.

· French pressure cell: extrusion.

· Freeze-thawed liposome’s.

· Lipid film hydration by hand shaking, non-handshaking or freeze drying.

· Micro-emulsification.

· Membrane extrusion.



· Dried reconstituted vesicles.

Sonication

Sonication is perhaps the most extensively used method for the preparation of SUV. Here,

MLVs are sonicated either with a bath type sonicator or a probe sonicator under a passive

atmosphere. The main disadvantages of this method are very low internal

volume/encapsulation efficacy, possible degradation of phospholipids and compounds to be

encapsulated, elimination of large molecules, metal pollution from probe tip, and presence of

MLV along with SUV. There are two sonication techniques:

- Probe sonication. The tip of a sonicator is directly engrossed into the liposome dispersion.

The energy input into lipid dispersion is very high in this method. The coupling of energy at

the tip results in local hotness; therefore, the vessel must be engrossed into a water/ice bath.

Throughout the sonication up to 1 h, more than 5% of the lipids can be de-esterified. Also,

with the probe sonicator, titanium will slough off and pollute the solution.

- Bath sonication. The liposome dispersion in a cylinder is placed into a bath sonicator.

Controlling the temperature of the lipid dispersion is usually easier in this method, in contrast

to sonication by dispersal directly using the tip. The material being sonicated can be protected

in a sterile vessel, dissimilar the probe units, or under an inert atmosphere.

French pressure cell: extrusion

French pressure cell involves the extrusion of MLV through a small orifice. 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 removal. The method involves gentle handling of

unstable materials. The method has several advantages over sonication method. 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).

Freeze-thawed liposomes

SUVs are rapidly frozen and thawed slowly. The short-lived sonication disperses aggregated

materials to LUV. The creation of unilamellar vesicles is as a result of the fusion of SUV

throughout the processes of freezing and thawing. This type of synthesis is strongly inhibited

by increasing the phospholipid concentration and by increasing the ionic strength of the

medium. The encapsulation efficacies from 20% to 30% were obtained.



2 Solvent dispersion method

Fig:2 Lipid Film Hydration Method

Ether injection (solvent vaporization)

A solution of lipids dissolved in diethyl ether or ether-methanol mixture is gradually injected

to an aqueous solution of the material to be encapsulated at 55°C to 65°C or under reduced

pressure. The consequent removal of ether under vacuum leads to the creation of liposomes.

The main disadvantages of the technique are that the population is heterogeneous (70 to 200

nm) and the exposure of compounds to be encapsulated to organic solvents at high

temperature.

Ethanol injection

A lipid solution of ethanol is rapidly injected to a huge excess of buffer. The MLVs are at

once formed. The disadvantages of the method are that the population is heterogeneous (30 to

110 nm), liposome’s are very dilute, the removal all ethanol is difficult because it forms into

azeotrope with water, and the probability of the various biologically active macromolecules

to inactivate in the presence of even low amounts of ethanol is high.



Reverse phase evaporation method

This method provided a progress in liposome technology, since it allowed for the first time

the preparation of liposomes with a high aqueous space-to-lipid ratio and a capability to

entrap a large percentage of the aqueous material presented. Reverse-phase evaporation is

based on the creation of inverted micelles. These inverted micelles are shaped upon

sonication of a mixture of a buffered aqueous phase, which contains the water-soluble

molecules to be encapsulated into the liposomes and an organic phase in which the

amphiphilic molecules are solubilized. The slow elimination of the organic solvent leads to

the conversion of these inverted micelles into viscous state and gel form. At a critical point in

this process, the gel state collapses, and some of the inverted micelles were disturbed. The

excess of phospholipids in the environment donates to the formation of a complete bilayer

around the residual micelles, which results in the creation of liposomes. Liposomes made by

reverse phase evaporation method can be made from numerous lipid formulations and have

aqueous volume-to-lipid ratios that are four times higher than hand-shaken liposomes or

multilamellar liposomes. Briefly, first, the water-in-oil emulsion is shaped by brief sonication

of a two-phase system, containing phospholipids in organic solvent such as isopropyl ether or

diethyl ether or a mixture of isopropyl ether and chloroform with aqueous buffer. The organic

solvents are detached under reduced pressure, resulting in the creation of a viscous gel. The

liposomes are shaped when residual solvent is detached during continued rotary evaporation

under reduced pressure. With this method, high encapsulation efficiency up to 65% can be

obtained in a medium of low ionic strength for example 0.01 M NaCl. The method has been

used to encapsulate small, large, and macromolecules. The main drawback of the technique is

the contact of the materials to be encapsulated to organic solvents and to brief periods of

sonication. These conditions may possibly result in the breakage of DNA strands or the

denaturation of some proteins. Modified reverse phase evaporation method was presented by

Handa et al., and the main benefit of the method is that the liposomes had high encapsulation

efficiency (about 80%).

3 Detergent removal method (removal of nonencapsulated material)

Dialysis

The detergents at their critical micelle concentrations (CMC) have been used to solubilize

lipids. As the detergent is detached, the micelles become increasingly better-off in

phospholipid and lastly combine to form LUVs. The detergents were removed by dialysis. A

commercial device called LipoPrep (Diachema AG, Switzerland), which is a version of



dialysis system, is obtainable for the elimination of detergents. The dialysis can beperformed

in dialysis bags engrossed in large detergent free buffers (equilibrium dialysis).

Detergent (cholate, alkyl glycoside, Triton X-100) removal of mixed micelles

(absorption)

Detergent absorption is attained by shaking mixed micelle solution with beaded organic

polystyrene adsorbers such as XAD-2 beads (SERVA Electrophoresis GmbH, Heidelberg,

Germany) and Bio-beads SM2 (Bio-Rad Laboratories, Inc., Hercules, USA). The great

benefit of using detergent adsorbers is that they can eliminate detergents with a very low

CMC, which are not entirely depleted.

Dilution

Upon dilution of aqueous mixed micellar solution of detergent and phospholipids with buffer,

the micellar size and the polydispersity increase fundamentally, and as the system is diluted

beyond the mixed micellar phase boundary, a spontaneous transition from polydispersed

micelles to vesicles occurs.

Drug loading in liposomes

Drug loading can be attained either passively (i.e., the drug is encapsulated during liposome

formation) or actively (i.e., after liposome formation). Hydrophobic drugs, for example

amphotericin B taxol or annamycin, can be directly combined into liposomes during vesicle

formation, and the amount of uptake and retention is governed by drug-lipid interactions.

Trapping effectiveness of 100% is often achievable, but this is dependent on the solubility of

the drug in the liposome membrane. Passive encapsulation of water-soluble drugs depends on

the ability of liposomes to trap aqueous buffer containing a dissolved drug during vesicle

formation. Trapping effectiveness (generally <30%) is limited by the trapped volume

delimited in the liposomes and drug solubility. On the other hand, water-soluble drugs that

have protonizable amine functions can be actively entrapped by employing pH gradients,

which can result in trapping effectiveness approaching 100%.

Purification of liposome

Liposomes are generally purified by gel filtration chromatography14, Dialysis and

centrifugation. In chromatographic separation, Sephadex-50 is most widely used. In dialysis

method hollow fibre dialysis cartridge maybe used. In centrifugation method, SUVs in

normal saline may be separated by centrifuging at 200000 g, for 10-20hours. MLVs are

separated by centrifuging at 100000g for less than one hour.



Mechanism of transportation through liposome[15,16]

The limitations and benefits of liposome drug carriers lie critically on the interaction of

liposomes with cells and their destiny in vivo after administration. In vivo and in vitro studies

of the contacts with cells have shown that the main interaction of liposomes with cells is

either simple adsorption (by specific interactions with cell surface components, electrostatic

forces, or by nonspecific weak hydrophobic) or following endocytosis (by phagocyte cells of

the reticulo endothelial system, for example macrophages and neutrophils). Fusion with the

plasma cell membrane by insertion of the lipid bilayer of the liposome into the plasma

membrane, with simultaneous release of liposomal content into the cytoplasm, is much rare.

The fourth possible interaction is the exchange ofbilayer components, for instance

cholesterol, lipids, and membrane-bound molecules with components of cell membranes.

Targeting of liposomes[12,20]

Two types of targeting.

1) Passive targeting

As a mean of passive targeting, such usually administered liposomes have been shown to be

rapidly cleared from the blood stream and taken up by the RES in liver spleen. Thus capacity

of the macrophages can be exploited when liposomes are to be targeted to the macrophages.

This has been demonstrated by successful delivery of liposomal antimicrobial agents to

macrophages. Liposomes have now been used for targeting of antigens to macrophages as a

first step in the index of immunity. For e.g. in rats the i.v. administration of liposomal antigen

elicited spleen phagocyte mediated antibody response where as the non liposome associated

antigen failed to elicit antibody response.

2) Active targeting

A pre requisite for targeting is the targeting agents be positioned on the liposomal surface

such that the interaction with the target i.e., the receptor is tabulated such as a plug and socket

device. The liposome physically prepared such that the lipophilic part of the connector is

anchored into the membrane during the formation of the membrane. The hydrophilic part on

the surface of the liposome, to which the targeting agent should be held in a stericaly correct

position to bond to the receptor on the cell surface.

Pharmacokinetics of liposomes[13]

- Liposomal drugs can be applied through various routes, but mainly i.v. and topical

administration is preferred. After reaching in the systemic circulation or in the local area, a

liposome can interact with the cell by any of the following methods.



- Endocytosis by phagocytotic cells of the R.E.S such as macrophages and Neutrophils.

-Adsorption to the cell surface either by non specific weak hydrophobic or electrostatic forces

or by specific interaction with cell surface components.

- Fusion with the plasma cell membrane by insertion of lipid bilayer of liposome into plasma

membrane with simultaneous release of liposomal contents into the cytoplasm.

-Transfer of liposomal lipids to cellular or sub cellular membrane or vice versa without any

association of the liposome contents.

- It is often difficult to determine what mechanism is operative and more than one may

operate at the same time.

Pharmocodynamics of liposomes encapsulated drugs[14]

To continue the action of drugs to a particular site in the body, the general approach is to

deposit drug bearing liposome directly into the site where therapy is desired. Since liposomes

are large and do not easily cross epithelial or connective barriers, they are likely to remain at

the site of local administration. The liposomes would then slowly released into the target site

or perhaps create a local drug level higher than the systemic level. Alternatively the drug

loaded liposomes might interact directly with cells in the target site, without producing

release. The goal of this approach is to maximize the amount of effective drug at the target

site, while minimizing the drug levels at other sites and thus decreasing systemic toxicity. For

e.g. SUV injected into the skin can persist interact at the site for 600 hrs. And release of

entrapped markers from the liposomes occurs only after cellular uptake and intracellular

space remain intact.

Evaluation of liposomes[11]

Liposomal formulation and processing for specified purpose are characterized to ensure their

predictable in-vitro and invivo performance. The characterization parameters for purpose of

evaluation could be classified into 3 broad categories which include physical, chemical, and

biological parameters.

-Physical characterization evaluates various parameters including size, shape, surface

features, lamellarty, phase behaviors and drug release profile.

-Evaluated structural integrity of Liposomal phospholipids membrane by a New technique of

gamma-ray perturb angular correlation (PAC spectroscopy.In this 111 Inlabelln diethyl

enetriaminepenta acetic acid (DTPA) Derivative dipalmitiylphosphatidylethanoamine(DPPE)

lipid were incorporated in the SUVs. This helped in the continuous non-invasive monitoring

of the microenvironment of the lipid bilayer.



-Chemical Characterization includes those studies which establish the purity and potency of

various lipophilic constituents.

-Biological Characterization parameters are helpful in establishing the safety and suitability

of formulation for therapeutic application.

1 Vesicle shape and Lamellarity

Vesicle shape can be assessed using Electron Microscopic Techniques. Lamellarity of

vesicles i.e. number of bilayer present in liposomes is determined using Freeze- Fracture

Electron Microscopy and P-31 Nuclear Magnetic Resosance Analysis.

2 Vesicle size and size distribution

Various techniques are described in literature for determination of size and size distribution.

These include Light Microscopy, Electron Microscopy (especially Transmission Electron

Microscopy), Laser light scattering Photon correlation Spectroscopy, Field Flow

Fractionation, Gel permeation and Gel Exclusion. The most precise method of determine size

of liposome is Electron Microscopy Since it permit one to view each individual liposome and

obtain exact information about profile of liposome population over the whole range of sizes.

Unfortunately, it is very time consuming and require equipments that may not always be

immediately to hand. In contrast, laser light scattering method is very simple and rapid to

perform but having disadvantage of measuring an average property of bulk of liposomes.

Another more recently developed microscopic technique known as atomic force microscopy

has been utilized to study liposome morphology, size, and stability. Most of methods used in

size, shape and distribution analysis can be grouped into various categories namely

microscopic, diffraction, Scattering, and hydrodynamic techniques.

1 Biological Characterization[17,18,19]

Table no:4

Characterization parameters Instrument for Analysis

Sterility Aerobic/Anaerobic Culture

Pyrogenicity Rabbit Fever Response

Animal toxicity Monitoring Survival Rats.



2 Physical Characterization

Table no:5

Characterization Parameters 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

Electrical surface potential and surface pH Zeta potential measurement and pH

sensitive probes.

Lamellarity p31 NMR

Phase behavior DSC , freeze fracture electron

microscopy

Percent Capture Mini column centrifugation

Drug release Diffusion cell/ dialysis

3 Chemical Characterization

Table no:6

Characterization

Parameters

Instrument for analysis

Phospholipids concentration HPLC

Cholesterol concentration HPLC/Cholesterol oxide assay

Phospholipids per oxidation U.V observation

pH pH Meter

Osmolarity osmometer

Stabilization of liposomes[17,18,19]

The stability of liposome should meet the same standard as conventional pharmaceutical

formulation. The stability of any pharmaceutical product is the capabilities of the delivery

system in the prescribed formulation to remain within defined or pre-established limits for

predetermined period of time.



- Chemical Stability involves prevention of both the hydrolysis of ester bonds in the

phospholipids bilayer and the oxidation of unsaturated sites in the lipid chain.

- Chemical instability leads to physical instability or leakage of encapsulated drug from the

bilayers and fusion and finally aggregation of vesicles.

- Introduced the proliposome concept of liposome preparation to avoid physicochemical

instability encountered in liposome suspension such asaggregation, fusion, hydrolysis and / or

oxidation.

- Approaches that can be taken to increase Liposomal stability involve efficient formulation

and lyophilization. Formulation involves the selection of the appropriate lipid composition,

concentration of bilayers, aqueous phase ingredients such as buffers, antioxidant, metal

chelators and cryo protectants. Charge inducing lipids such as phosphotidyl glycerol can

beincorporated into liposome bilayers to decrease permability and leakage of encapsulated

drugs. Buffers at neutral pH can decrease hydrolysis ,addition of antioxidant such as sodium

ascorbate can decrease oxidation.

Marketed Preparation[6]

Table no:7

Name Trade name Company Indication

Liposomal

Amphotericin B

Ablect Enzon Fungal infection

Liposomal

Amphotericin B

Ambisome Gilead Sciences Fungal and

protozoval infection

Liposomal

cytarabine

Depocyt Pacira(Sky pharma) Malignant

lymphomatous

meningitis

Liposomal

daunorubicin

Dauno Sciences Gilead Sciences HIV-related

Kaposi’sarcoma

Application of Liposomes[1,2,7,22]

1. Liposome as drug/protein delivery vehicle:

Controlled and sustained drug release in situ

Enchaned drug solubilization

Altered pharmacokinetic and biodistribution

Enzyme replacement therapy and lysosomal disorders

2. Liposome in antimicrobial, antifungal and antiviral therapy:

Liposomal drugs

Liposomal biological response modifier



3. Liposomes in tumour therapy:

Crrrier of small cytotoxic molecule

Vehicle for macromolecule as cytokines or genes

4. Liposome in gene therapy:

Gene and antisence therapy

Genetic (DNA) vaccination

5. Liposome in immunology:

Immunoadjuvant

Immunomodulator

Immunodiagnosis

6. Liposome as artificial blood surrogates.

7. Lipososmes as radiopharmaceutical and radiodiagnostic carrier.

8. Liposomes in cosmetics and dermatology.

9. Liposomes in enzyme immobilization and bioreactor technology.

10. Liposomes enhanced the drug uptake via endocytosis.

11. Liposomes can be used as carrier of drug in oral treatment of

a. Arthritis

Treated with steroids using MLVs prepared by DPPC and P.A.

E.g. Drugs are Ibuprofen, cortisol palmitate

b. Diabetes

Alternation in blood glucose level in diabetic animals was obtained by oral administration of

liposome encapsulated insulin.

Limitation in liposome technology:

1) Stability

2) Sterilization

3) Encapsulation efficiency

4) Active targeting

5) Gene therapy

6) Lysosomal degradation

CONCLUSION:

Liposomes have been used in a broad range of pharmaceutical applications. Liposomes are

showing particular promise as intracellular delivery systems for anti-sense molecules,

ribosomes, proteins/peptides, and DNA. Liposomes with enhanced drug delivery to disease



locations, by ability of long circulation residence times, are now achieving clinical

acceptance. Also, liposomes promote targeting of particular diseased cells within the disease

site. Finally, liposomal drugs exhibit reduced toxicities and retain enhanced efficacy

compared with free complements. However, based on the pharmaceutical applications and

available products, we can say that liposome’s have definitely established their position in

modern delivery systems. The use of liposomes in the delivery of drugs and genes are

promising and is sure to undergo further developments in future.

REFERENCES:

1. JainN.K.Controller and Novel Drug Delivery.CBS Publisher and disributors, New

Delhi.2009; Vol-1,- 278,283,305.

2. Brahmankar D.M, Jaiswal S.B. Biopharmaceutices and Pharmacokinetices

2nd

ed.2009: 481.

3. Saraswathi Marripati,K. Umashankar,P. JayachandraReddy.A Review On Liposomes,

International Journal of Research In Pharmaceutical And Nano Sciences.2014; 3(3),-

159-169.

4. T.V.Thulasiramaraju,A.M.SudhakarBabu, A.Arunachalam.Liposomes A Novel Drug

Delivery System. International Journal of Biopharmaceutices.2012; 3(1),-5-16.

5. Mansoori M.A, Agrawal S.,Jawade S., Khan M.,I.A Review On Liposomes.

International Journal of Advanced Research In Pharmaceutical & Biosciences.2012;

2(4), 453-464.

6. Loveleenpreet Kaur, P., rabhjotKaur.Liposomes As A Drug Carrier A

Review.International Journal of Research In Pharmacy And Chemistry.2013; 3(1),

121-127.

7. Vyas S.P.,KharK.R.,Targeted and Controlled Drug Delivery. CBS Publisher and

Distributors,New Delhi.2002; 1, 181-187.

8. Torchilin V. et.al Multifunctional nanocarriers, Advanced Drug Delivery Reviews,

58(14), 2006, 1532-55.

9. Yash Roy R C. Lamellar dispersion and phase separation of chloroplast membrane

lipids by negative staining electron microscopy, Journalof Biosciences, 15(2), 1990,

93-98.

10. Barani H, Montazer M. A review on applications of liposomes in textile processing,

Journal of liposome research, 18(3), 2008, 249-262.



11. Szoka J R, et.al .Comparative properties and methods of preparation of lipid vesicles

(liposomes).Annual review of biophysics and bioengineering, 9, 1980, 467–508.

12. Riaz.M. Liposomes preparation method. pakisthan journal of pharmaceutical

sciences. 1996; 19(1); 65-77.

13. Anwekar H. Liposome as drug carriers. International journal of pharmacy and life

science.2011; 2(7); 945-951.

14. Sharma A.Liposome in drug delivery progress and limitation.International journal of

pharmaceutics.1997; 154; 123-140.

15. LasicD.et.al Mechanism of liposome formation .Journal of liposome research. 1995;

5(3); 431-441.

16. Anwekar H, et.al Liposome as drug carriers. International journal of pharmacy and

life science.2011; 2(7); 945-951.

17. Sharma Shailesh. et.al. Liposomes a review. Journal of pharmacy research. 2009;

2(7); 1163-1167.

18. Kataria S. Stealth.et.al liposomes a review. International journal of research in

ayurveda and pharmacy. 2011; 2(5); 1534-1538.

19. Abdus S. et.al Liposome drug delivery system an update review. Current drug

delivery.2007; 4; 297-305.

20. Patel M. et.al Liposomes as a topical drug delivery system. International journal of

pharmaceutical and life science.2012; 1(1); 1-10.

21. B.V.Mikari; S.A.Korde.formulation and evalution of topical Liposomal gel for

fluconazole, Indian journal of pharmaceutical education and research; 2010; 44(4);

324-325.

22. Remington “The Science and Practice of pharmacy”, vol. 1,21st edition, B.I

publishers Pvt Ltd, -314-316.

AN OVERVIEW ON LIPOSOMES: A NOVEL DRUG DELIVERY SYSTEM. RPA1516256015.pdf · an overview on...

Documents

Transcript of AN OVERVIEW ON LIPOSOMES: A NOVEL DRUG DELIVERY SYSTEM. RPA1516256015.pdf · an overview on...