Liposome&nanoparticles .mla

MUTHUMAHARAJA MLA DEPARTMENT OF PHARMACEUTICS1

Contents of liposomes& nanoparticles
LIPOSOME
 Introduction
 Mechanism of liposome formation.
 Classification.Methods of preparation.
 Characterization.
 Applications and Commercial products.
NANOPARTICLES
 Preparation methods.
 Novel nanoparticulate system.
 Surface engineering of nanoparticles.
 Characterization.
 Applications.Commercial products.

Introduction;
 Liposomes are targeted drug delivery systems consisting of one or more
concentric spheres of lipid bilayers separated by water or aqueous buffer
compartments composed of natural or synthetic phospholipids.

MECHANISM OF LIPOSOMAL FORMATION:

MECHANICAL DISPERSION:
Lipid film hydration by hand shaking/non hand
shaking:

Micro-emulsification:

French pressure cell:

Dried reconstituted vesicles and freeze thaw sonication:

SOLVENT DISPERSION:
Ethanol and Ether injection:

Reverse phase evaporation vesicles:

DETERGENT DEPLETION(REMOVAL) METHODS:
Detergents associate with the phospholipid molecules and serve to
screen the hydrophobic portions of of molecule from water.
The structures formed as a result of this association is known as
micelles.
A three stage model of interaction for detergents with lipidbilayers:
Stage1: At low concentration detergents equilibratesbetween
vesicular lipid and water phase.
stage2: After reaching a critical detergent concentration,membrane
structure tends to unstable and transforms gradually in to micelles.
stage3: All lipid exists in mixed micelleform.
Three methods are applied for removal of detergent and transition
of mixed micelles to concentric bilayered form.

Removal of unentrapped drug from liposomes:
It is important to estimate the amount of drug encapsulated within
liposomes.
This is easier to estimate by centrifugation in case of MLVs
compared to LUVs and SUVs.
The various methods used to separate non-encapsulated drug are
eg: Dialysis.
Gel chromatography.

Characterization:
VESICLE SIZE AND SIZE DISTRIBUTION:
Microscopy .
Gel chromatography.
LAMELLARITY:
Freeze fracture and freeze-etch electron microscopy.
31 P NMRanalysis.
SURFACE CHARGE:
Free flow electrophoresis

Zeta potential method.

TRAP PED VOLUME:
The internal or trapped volume is the aqueous entrapped volume per
unit quantity of lipid and expressed as µl/mol.
The entrapped volume is determined using various materials like
inert fluid-D2O, radioactive markers- 22Naor 14C and fluorescent
markers- 6-carboxyfluorescein.
PHASE BEHAVIOR OF LIPOSOMES:
Membrane phospholipids undergo temperature dependent reversible
phase transitions from gel to liquid crystaline state.
These have been documented by freeze fracture electron
microscopy and DSC.
Tm of the phospholipid affects the membrane permeability, leakage
and stability of liposomes.

Tm can be altered by using phospholipid mixtures or by adding
cholesterol.

CHEMICAL CHARACTERIZATION:
PARAMETERS ANALYTICAL METHOD
Phospholipid concentration Barlett assay/stewart assay, HPLC
Cholesterol concentration Cholesterol oxidase assay,HPLC
Phospholipid hydrolysis HPLC,TLC and Fatty acid concentration
Phospholipid oxidation UV and GLC

APPLICATIONS:
 Liposomes as drug or protein delivery vehicles.
Liposome in antimicrobial, antifungal(lung therapeutics) and antiviral
(anti HIV) therapy.
 In tumour therapy.
 In gene therapy.
 In immunology.
 Liposomes as artificial blood surrogates.
 Liposomes as radiopharmaceutical and radiodiagnostic carriers.

 Liposomes in cosmetics and dermatology.

COMMERCIAL PRODUCTS:
 Doxorubicin(DOXIL).
 Daunorubicin(DAUNOXOME).
 AmphotericinB(APHOTEC, AMBISOME, ABELCET).
Cytarabine(DEPOCYTE).

NANOPARTICLES:
INTRODUCTION:
Nanoparticles are sub- nano sized colloidal structures composed of
synthetic or semi synthetic polymers with a size smaller than 1mm.
The term nanoparticles include
NANOSPHERE NANOCAPSULE

POLYMERS:
Natural polymers:
PROTEINS POLYSACCHARIDES
Gelatin Alginate
Albumin Dextran
Lectins Chitosan
Legumin Agarose
vicilin pullulan
Synthetic polymers:
PRE- POLYMERIZED POLYMERIZED IN PROCESS
Poly(Ɛ-caprolactone) Poly(isobutylcyanoacrylates)
Poly lactic acid Poly(butylcyanoacrylate)

Ploy(lactic-co-glycolide) Polyhexylcyanoacrylate
polystyrene Poly methyl methacrylate

Amphiphilic
macromolecule
crosslinking
Polymerization
based methods
Ploymer
precipitation
methods
•Heat cros-linking.
•Chemical cross-
linking
•Solvent
extraction/evaporation.
•Solventdisplacement
or nanoprecipitation.
•Salting out.
•Polymerization of monomers.
•Emulsion polymerization.
•Dispersion polymerization.
•Interfacialcondensation
polymerization.
•Interfacial complexation.
METHODS OF PREPARATION

MACROMOLECULAR CROSS LINKING IN A WATER IN
OIL EMULSION:
or h
W/O emulsion
Dilution with preheated oil (100oC)
(Heat cross-linking)
Or Addition of crosslinking agent
(Chemical cross-linking)
a O

Centrifugation and isolation of
nanoparticles

POLYMERIZATION OF MONOMERS:
High pressure homogenization
Monomer B
Water+ monomer A Oli phase
w/o emulsion.
Nanocapsules.

MICELLAR PLOYMERIZATION MECHANISM:

DISPERSION POLYMERIZATION:
Oligomers aggregate &
precipitates
Heated to above 65 C
(Acrylamide or Methyl methacrylate) Monomer is dissolved
in an aqueous medium
Further, By chemical initiation
(ammonium or potassium per oxo disulphate)

lsolation of nanospheres

INTERFACIAL POLYMER CONDENSATION:
Non-solvent which precipitate
polymer from either of the phases
o/w emulsion.
Ploymer phaseCore phase + drug
Nanocapsules.
(30-300nm)

INTERFACIAL COMPLEXATION:
Competing polyelectrolyte
Polymer complexation
Polyelectrolyte. Reverse micelle
nanoparticles.

SOLVENT EVAPORATION METHOD:
Sonication, homogenization
Solvent extraction, solvent evaporation.
Organic phase solvent,
drug, polymer.
Aqueous phase distilled
water, stabilizer.
o/w emulsion
Nanoparticles.

Double emulsion solvent evaporation method:
Sonication, homogenization
Aqueous phase with stabilizer
Solvent extraction, solvent evaporation
Organic phase solvent,
drug, polymer.
Aqueous phase
distilled water,
Stabilizer.
w/o emulsion
stabilized at
4oc
w/o/w emulsion.

Nanoparticles.

Organic solvent,
polymer, drug
Distilled water,
polaxamer 188
SOLVENT DISPLACEMENT METHOD:
Magnetic stirring
Distilled water,
polaxamer
188
Nanospheres. Nanocapsules.
Polar solvent, oil,
polymer, drug.

SALTING OUT:
Mechanical stirring
Distilled water
Organic solvent,
drug, polymer.
Distilled water,
PVA, MgCl2
o/w emulsion.
Nanoparticle.

SURFACE ENGINEERED NANOPARTICLES
STEARICALLY STABILIZED (STEALTH) NAOPARTICLES:
The surface modification of particulate carriers is achieved by
coating or grafting to nanoparticle surface with certain materials that
impart stealth behaviour.
eg:Polaxamers.
Polaxamines.
BIO-MIMETIC NANOPARTICLES:
These are the nanoparticles coated with endogenous serum
components which prevent their uptake through mononuclear
phagocytic system.
eg:Albumin.

Orosomucoid.

NANOPARTICLES COATED WITH ANTIBODIES:
Anchoring of targeted specific antibodies to the nanoparticle
surface may facilitate the delivery to specific sites.
eg: Monoclonal antibodies.
MAGNETIC NANOPARTICLES:
Nanoparticles are rendered magnetic by incorporating Fe3O4
simultaneously with drug during the preparation stage, injected
through the artery is guided by the external magnet inorder totarget
the site.
BIOADHESIVE NANOPARTUCLES:
Drugs are associated to polymeric bioadhesive nanoprticulate system
as they adhere to the mucosal surface provide better drug absorption.

eg: lectin.

CHARACTERIZATION
PARTICLE SIZE AND SIZE DISTRIBUTION:
Photon correlation spectroscopy.
Scanning electron microscopy.
Transmission electron spectroscopy.
SURFACE CHARGE:
The surface charge of nanoparticle is determined by measuring the
particle velocity in an electric field.
Laser Doppler Anemometry.
SURFACE HYDROPHOBICITY:

Hydrophobic interaction chromatography.
 Two phase partitioning technique.

APPLICATIONS
Nanoparticles in chemotherapy.
Nanoparticles in intracellular targeting.
Nanoparticles for ocular and brain delivery.
Nanoparticles for DNA delivery.
Nanoparticles for oligonucleotide delivery.
Nanoparticles for lymph targeting.

Nanoparticles for peroral administration of protein and peptide.

COMM
ED
Rau
Cn
Io
Ax
Lom
Pe
RR
O- A
Dn
Utic
Ca
Tnc
Ser.
GendicineR – Genedelivery.
AmphoteR –Antifungal.
.
AmbraxaneR –Anticancer.
DoxilR -Anticancer
Nanoxel.

REFERENCE
 Deepak Thassu, Michel Deleers, “Nanoparticulate Drugdelivery
systems,” vol-166. pg.no:89.
 Herbert A.Lieberman, Martin M.Rieger and Gilbert S.Banker,
“Pharmaceutical dosage forms: Disperse systems,” vol-3. 2nd edition.
Pg.no:43-83 & 87-119.

Liposome&nanoparticles .mla

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