Targeted Drug Delivery System Unit-IV DrNitalikar

1
UNIT-IV
Targeted Drug Delivery System
Dr. Manojkumar M. Nitalikar
Dept. of Pharmaceutics,
Rajarambapu College of Pharmacy,
Kasegaon

1. Concepts and approaches
2. Advantages and disadvantages
3. Introduction to
a. Liposomes
b. Niosomes
c. Nanoparticles
d Monoclonal antibodies
Their applications
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CONTENTS

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INTRODUCTION
‘A special form of drug delivery system where
the medicament is selectively targeted or
delivered only to its site of action or
absorption and not to the non-target organs
or tissues or cells.’

4
INTRODUCTION
• Method of delivering medication to a patient in a manner
that increases the concentration of the medication in some
parts of the body relative to others.
• Seeks to concentrate the medication in the tissues of
interest while reducing the relative concentration of the
medication in the remaining tissues.
• This improves efficacy and reduce side effects.

5
CONCEPT
 Introduced by Paul Ehrlich (1902) as “Magic Bullet”.
 Alec Bangham (1965) observed phospholipid hexagonal
liquid crystals, were perselective to the ions as like bio
membrane.
 Led to discover the newer molecules (artificial vesicles)
based on phospholipids amphiphiles are called Banghams
liposomes or banghosomes.
 Later Gregoriadis (1981) described drug targeting by
the name of “older drugs in newer clothes” as Novel
Drug Delivery System.

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INTRODUCTION
Targeted drug delivery system is preferred over
conventional drug delivery systems due to three main
reasons.
1. Pharmaceutical reason. Conventional drugs have low
solubility and more drug instability in comparison to
targeted drug delivery systems.
2. Pharmacokinetic properties: Conventional drugs have
poor absorption, shorter half-life and require large
volume of distribution.
3. Pharmacodynamic properties: Conventional drugs
have low specificity and low therapeutic index as
compared to targeted drug delivery system.

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INTRODUCTION
Targeted drug delivery system is preferred over
conventional drug delivery systems due to three main
reasons.

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IDEAL CHARACTERISTICS OF TDDS
 Should be nontoxic, biocompatible, biodegradable, and
physicochemical stable in vivo and in vitro.
 Restrict drug distribution to target cells or tissues or
organs and should have uniform capillary distribution.
 Controllable and predictable rate of drug release.
 Should have therapeutic amount of drug release.
 Minimal drug leakage during transit.
 Carriers used should be bio-degradable or readily
eliminated from the body.
 Formulation of the delivery system should be easy or
reasonably simple, reproductive and cost effective.

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ADVANTAGES
 Reduces the side effects and toxicity.
 Dose of the drug reduces by targeting organ.
 Avoids the degradation of drug (first pass
metabolism).
 Drug bioavailability increases and fluctuation in
concentration decreases.
 It also has positive effect on permeability of proteins
and peptide.
 Reduction in dosage frequency and hence reduce
the cost of expensive drug.

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DISADVANTAGES
 Rapid clearance of targeted systems.
 Immune reactions against intravenous administered
carrier systems.
 Insufficient localization of targeted systems into tumour
cells.
 Diffusion and redistribution of released drugs.
 Requires highly sophisticated technology for the
formulation.
 Requires skill for manufacturing storage, administration.

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Types of Targeted Drug Delivery
1 Active targeting
2 Passive targeting
3 Inverse targeting
4 Dual targeting
5 Double targeting
6 Combination targeting
7. Ligand mediated targeting

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Liposomes
 Simple microscopic, concentric bilayered vesicles in
which an aqueous volume is entirely enclosed by a
membranous lipid bilayer mainly composed of natural
or synthetic phospholipids.
 Discovered in 1960‟s by Bangham and coworkers.
 Main Structural components are phospholipids and
cholesterol

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Liposomes
Structurally, liposomes are bilayered vesicles in which
an aqueous volume is entirely enclosed by a
membranous lipid bilayer mainly composed of natural
or synthetic phospholipids
These vesicles can encapsulate water-soluble drugs in their
aqueous spaces and lipid soluble drug within the membrane
itself.
Unique property of liposomes, namely their versatile,
biodegradable, hypoallergenic nature, along with their
similarity to biological membranes

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Advantages of Liposomes
 Provides selective passive targeting to tumor tissues
 Increased efficacy and therapeutic index
 Increased stability via encapsulation
 Reduction in toxicity of the encapsulated agent
 Improved pharmacokinetic effects
 Used as carriers for controlled and sustained drug
delivery
 Can be made into variety of sizes.

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Disadvantages of Liposomes
 Leakage of encapsulated drug during storage.
 Batch to batch variation
 Difficult in large scale manufacturing and sterilization
 Once administered, liposomes can not be removed
 Possibility of dumping, due to faulty administration
 High production cost
 Allergic reactions may occur to liposomal constituents
 Less stability

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Classification of Liposomes
On the basis of structural parameters:
 Multilamellar vesicles (> 0.5 um) MLV
 Oligolamellar vesicles (0.1-1 um) OLV
 Unilamellar vesicles (all size range) UV
 Small unilamellar vesicles (20-100 nm) SUV
 Medium sized unilamellar vesicles MUV
 Large unilamellar vesicles (> 100 um) LUV
 Giant unilamellar vesicles (>1 um) GUV
 Multi vesicular vesicles (>1 um) MVV
On the basis of liposome preparation:
 Vesicles prepared by reverse phase evaporation method REV
 Multi lamellar vesicle by REV MLV-REV
 Stable plurilamellar vesicle SPLV
 Frozen & thawed MLV FATMLV
 Vesicles prepared by extrusion techniques VET
 Dried reconstituted vesicles DRV

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Different Types of Liposomes

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Methods of preparation of Liposomes
Physical dispersion method:-
1. Hand shaking MLVs
2. Non-shaking LUVs
3. Freeze drying
4. Pro-liposomes
Solvent dispersion method :
1. Ethanol injection
2. Ether injection
3. Water organic phase:
A) Double emulsion method
B) Reverse phase evaporation
C) Stable plurilamellar vesicles
Detergent solubilization

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Hand shaken MLV’s
Lipids + solvent ( chloroform: Methanol)
( In 250 ml RBF)
Evaporate for 15 min above phase transition temperature
(Flush with nitrogen)
Till residues dry
Add 5 ml buffer containing material to be entrapped
Rotate flask at room temp, at 60 RPM for 30 min until lipid
removes from wall of RBF
Milky white dispersion (stand for 2 hours to get MLV)

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ROTARY EVAPORATOR

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SOLVENT DISPERSION METHODS
Ether Injection Method
Solution of lipids dissolved in diethyl ether or ether/methanol mixture
slowly injected at 55-65°C
or under reduced pressure
Aqueous solution of the material to be encapsulated
Removal of ether under vacuum leads to the formation of liposomes

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Ethanol Injection Method
Solution of lipids in ethanol
slowly injected at 55-65°C
or under reduced pressure
Buffer
MLVs are formed
https://www.youtube.com/watch?v=vUqwIL5lgS8
https://www.youtube.com/watch?v=6oml_EArMo8

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Ethanol /Ether Injection Method

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Characterization/ Evaluation of Liposomes
C) Biological Characterization:
1. Sterility testing
2. Pyrogenicity testing.
3. Animal toxicity
A) Physical Characterization:
1. Entrapement efficiency
2. Vesicle shape & morphology
3. Lamellarity
4. Particle size & size distribution
5. Surface charge
6. Phase transition behaviour
7. Drug release
B) Chemical Characterization:
1. Phospholipid concentration
2. Cholesterol concentration
3. Lysolecithin concentration
4. Phospholipid peroxidation
5. Phospholipid hydrolysis &
Cholesterol autooxidation
6. pH of liposomal dispersion.
7. Osmolarity
D) Stability testing:

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Applications of Liposomes
 As drug or protein delivery vehicles
 In antimicrobial, antifungal(lung therapeutics) and
antiviral (anti HIV) therapy
 In tumour therapy
 In gene therapy
 In immunology
 As vaccine carrier
 As radiopharmaceutical and radiodiagnostic carriers.
 In cosmetics and dermatology

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Marketed Preparations of Liposomes
Product Name Drug Delivered Approved Treatment
Myocet Doxorubicin Breast Cancer
Doxil Doxorubicin Breast Cancer
Lipodox Doxorubicin Breast Cancer
Marquibo Vincristine Sulphate Acute Lymphoblastic
Leukemia
Ambisome Amphotericin B Fungal Infection
Visudyne Verteporfin Age related molecular
degeneration
DepoDur Morphine Sulphate Pain

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Introduction
Vesicular drug delivery reduces the cost of therapy by
improving bioavailability of medication and also solves
the problems of drug insolubility, instability and rapid
degradation
Novel drug delivery system, in which the medication is
encapsulated in a vesicle.
Vesicle is composed of a bilayer of non-ionic surface
active agents and hence the name niosomes.
Very small, and microscopic in size.
Size lies in the nanometric scale.
Niosomes

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Niosomes are synthetic microscopic vesicles consisting
of an aqueous core enclosed in a bilayer consisting of
cholesterol and one or more nonionic surfactants
Vesicles are prepared from self assembly of hydrated
non ionic surfactants molecules.
Introduction
Definition

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Components of Niosomes
Surfactants:
 Non-ionic surfactants are used.
 Considered the important structural component.
 Act as Vesicle Forming Agents.
Nature of vesicles formed depends upon HLB value and phase
transition temperature.
 HLB value is a good indicator to predict the vesicle
formation and entrapment efficiency.
 HLB number in between 4 and 8 is compatible with vesicle
formation.
 Higher Phase transition temperature (TºC): More likely in the
ordered gel form forming less leaky bilayer, Having higher
entrapment efficiency, while surfactants of lower T° C are more
likely in the less ordered liquid form.
Spans, Tweens and Brijs

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Cholesterol:
 Acts as “vesicular cement” in the molecular space that
formed by the aggregation of monomer to form the bilayer.
Increases the rigidity and decreases the permeability of
drug through the membrane and hence improves the
entrapment efficiency.
 Also act stabilizing agent.

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Solvents:
 Act as penetration enhancer and affect the vesicular size
formation.
 E.g. Alcohols: Ethanol, Propanol, Butanol, Isopropanol.
 Ethanol showed larger vesicular size due to the slow phase
separation as it has greater solubility in water, whereas due to the
branching of isopropanol it showed smaller vesicular size.
 Drug penetration is maximal for isopropanol due to the branched
structure will act as co-surfactant and might loosen the bilayer
packing resulting into the increased release of drug. Also act
stabilizing agent.

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Structure of Niosomes
Microscopic lamellar structures, which are formed on the
admixture of non-ionic surfactant (alkyl or dialkyl
polyglycerol ether class) and cholesterol with subsequent
hydration in aqueous media.
Structurally, niosomes are similar to liposomes, in that they
are also made up of a bilayer. However, the bilayer in the
case of niosomes is made up of non-ionic surface active
agents rather than phospholipids as seen in the case of
liposomes.
Niosome is made of a surfactant bilayer with its hydrophilic
ends exposed on the outside and inside of the vesicle, while
the hydrophobic chains face each other within the bilayer.
Hence, the vesicle holds hydrophilic drugs within the
space enclosed in the vesicle, while hydrophobic drugs are
embedded within the bilayer itself.

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Structure of Niosomes
Hydrophobic drug
Hydrophilic Drug
Bilayer
Hydrophobic Tail
Hydrophilic Head
Ligand

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Niosome Liposome
1. Less expensive More expensive
2. Chemically Stable Chemically unstable
3. Niosomes are prepared from
uncharged single chain
surfactant
Liposomes are prepared from
double chain phospholipids
4. They do not require special
storage and handling
They require special storage ,
handling and purity of natural
phospholipid is variable.
5. Non ionic drugs carriers are
safer.
Ionic drugs carriers are safer are
relatively toxic & unsuitable
Similarity Liposomes and Niosomes

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Advantages of Niosomes
 Are osmotically active, chemically stable and have long
storage time compared to liposomes
 Surface formation and modification is very easy
because of the functional groups on their hydrophilic
heads
 Have high compatibility with biological systems and low
toxicity because of their non-ionic nature
 Biodegradable and non-immunogenic
 Entrap lipophilic drugs into vesicular bilayer membranes
and hydrophilic drugs in aqueous compartments

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Advantages of Niosomes
 Act as a depot, releasing the drug in a controlled manner
 Handling and storage requires no special conditions
 Improved oral bioavailability of poorly absorbed drugs and
enhance skin penetration of drugs.

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Disavantages of Niosomes
 Aqueous suspension of niosome may exhibit fusion,
aggregation, leaching or hydrolysis of entrapped drug, thus
limiting the shelf life of niosome dispersion
 Time consuming
 Requires specialized equipment

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Common Stages in Preparation of Niosomes
Cholesterol + Non Ionic Surfactant
Dissolve in organic solvent
Solution in organic solvent
Thin Film
Drying
Niosome suspension
Dispersion (Hydration)

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Preparation Methods of Niosomes
1. Ether injection method
2. Hand shaking method
3. Sonication Method
4. Micro fluidization method
5. Multiple membrane extrusion method
6. Reverse Phase Evaporation Technique
7. Transmembranes pH gradient (inside acidic)
Drug Uptake Process
8. Bubble Method

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Ether injection method:
 Based on slowly introducing a solution of surfactant
dissolved in diethyl ether into warm water maintained at
60°C.
 Surfactant mixture in ether is injected through 14-
gauge needle into an aqueous solution of material.
 Vaporization of ether leads to formation of single
layered vesicles.
 Particle size of the niosomes formed depend on the
conditions used the diameter of the vesicle range from
50 to 1000 nm.

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Ether injection method:
o o

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Hand shaking method (thin film hydration
technique):
 Surfactant and cholesterol are dissolved in a
volatile organic solvent (diethyl either, chloroform or
methanol) in a round bottom flask.
 Organic solvent is removed at room temperature
(20°C) using rotary evaporator leaving a thin layer
of solid mixture deposited on the wall of the flask.
 Dried surfactant film can be rehydrated with
aqueous phase at 0-60°C with gentle agitation to
yield multilamellar niosomes.

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Hand shaking method (thin film hydration
technique):

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Sonication Method
Aliquot
of drug
solution
in buffer
Added to the
surfactant/
cholesterol
mixture in a
10 ml glass
vial
Mixture is probe
sonicated at
600C for 3 min
using sonicator
with titanium
probe to yield
niosomes
Bath Sonicator
Probe Sonicator
SUVs
Small MLVs

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Micro fluidization Method
 Recent technique to prepare small multi lamellar
vesicles.
 Microfludizer is used to pump the fluid at a very high
pressure (10,000 psi) through a 5 pm screen.
 Forced along defined microchannels, which direct
two streams of fluid to collide together at right angles,
thereby affecting a very efficient transfer of energy.
 Lipids can be introduced into the fluidizer.
 Fluid collected can be recycled through the pump
until vesicles of spherical dimensions are obtained.
 Niosomes with greater uniformity and small size
which shows better reproducibility.

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Micro fluidization Method

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Multiple Membrane Extrusion Method
 Size of niosomes is reduced by passing them
through membrane filter.
 Method can be used for production of multi lamellar
vesicles as well as large unilamellar vesicles. It is found
as a good method for controlling niosomal size.

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Reverse Phase Evaporation Technique
 Key in this method is the removal of solvent from an
emulsion by evaporation.
 Surfactant and cholesterol are dissolved in ether or
chloroform or in a mixture of chloroform and ether with
or without drug.
 Resulting two-phase system is then homogenized
using homogenizer.
 Organic phase is removed under reduced pressure to
form niosomes dispersed in aqueous phase.

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Reverse Phase Evaporation Technique

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Trans membrane pH gradient drug uptake process:
 Organic phase with dissolved components is
evaporated to form a thin layer and hydrated with
citric acid
 Multilamellar vesicles are formed which are freeze
thawed 3 times and sonicated.
 To this Niosomal suspension aqueous solution with
drug is added, vortexed and pH is raised upto 7.0-
7.2 with 1M disodium phosphate.
 Mixture is heated at 60° C for 10 minutes to get
drug loaded niosomes

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Trans membrane
pH gradient
Drug uptake process:
Freeze

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 One step preparation of liposomes and Niosomes without the
use of organic solvents.
 Bubbling unit consists of round bottomed flask with three necks
positioned in water bath to control the temperature.
 Water cooled reflux and thermometer is positioned in the first
and second neck and nitrogen supply through third neck.
 Cholesterol and surfactant are dispersed together in buffer
(pH7.4) at 700C, the dispersion mixed for 15 sec. with high shear
homogenizer and immediately afterwards “bubbled” at 700C
using nitrogen gas.
Bubble method:

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Bubble method:

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Applications of Niosomes
 Drug Targeting.
 In Anti- Neoplastic Treatment i.e. Cancer Disease
e.g. Methotrexate
 In Leishmaniasis i.e. Dermal and Mucocutaneous
infections e.g. Sodium stibogluconate.
 In delivery of peptide drugs.
 Transdermal Drug Delivery Systems Utilizing Niosomes.
e. g. Erythromycin
 Used in Ophthalmic drug delivery. e.g. Cyclopentolate

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Nanoparticles
What are nanoparticles ?
Nano' derives from the Greek word “nanos”
which means dwarf or extremely small.
It can be used as a prefix for any unit to mean a
billionth of that unit.
Nanosecond : Billionth of a second.
Nanoliter : Billionth of a liter.
Nanometer : Billionth of a meter or 10-9 m.
Billion: 1,000,000,000 or 109

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Coarse particle – smaller than 10 μm
Fine particle – smaller than 2.5 μm
Ultrafine particle – smaller than 0.1 μm (100nm)
Nanoparticles
Nanoparticle
– dimensions between 1 nm and 100 nm

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Nanoparticles
Solid colloidal particles ranging from 1 to 1000
nm in size
Consist of micromolecular materials in which the
active ingredients (drug or biologically active
material) is dissolved, entrapped, or
encapsulated, or adsorbed, or attached.

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Nanoparticles
Nanoparticles
Nanospheres Nanocapsules
Matrix type
structure in
which a drug
is dispersed
Membrane wall
structure with
an oil core
containing drug

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Nanoparticles
Nanoparticles
Nanosheres Nanocapsules

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Nanoparticles
Nanoparticles
Nanosheres Nanocapsules

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Advantages of Nanoparticles
o Site-specific delivery of drugs.
o Helps to achieve maximum therapeutic response with
minimum adverse effects.
o Active and passive drug targeting can be achieved by
manipulating the particle size and surface characteristics
of nanoparticles.
o Can be administrated by parentral, oral, nasal (or)
occular routes.
o By attaching specific ligands onto their surfaces,
nanparticles can be used for directing the drugs to
specific target cells.

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Advantages of Nanoparticles
o Have higher stabilities
o Have higher drug carrier capacity
o Feasibility of incorporation of both hydrophilic and
hydrophobic substances
o Biodegradable, non-toxic and capable of being stored
for longer periods.
o Used for controlled delivery of drugs
o Reduces dosing frequency

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Disadvantages of Nanoparticles
o Limited drug loading.
o Susceptible to bursting and leakage of contents.
o Small size and large surface area lead to particle
aggregation.
o Handling of nanoparticles is difficult in liquid and dry
forms.

68
Preparation of Nanoparticles
1. Emulsion-Solvent Evaporation Method
2. Double Emulsion and Evaporation Method
3. Salting Out Method
4. Emulsions- Diffusion Method
5. Solvent Displacement / Precipitation Method

69
1. Emulsion-Solvent Evaporation Method:
Most frequently used methods for the preparation of
nanoparticles.
Involves two steps.
First step requires emulsification of the polymer solution
into an aqueous phase.
Second step polymer solvent is evaporated, inducing
polymer precipitation as nanospheres.
Nanoparticles - Collected by ultracentrifugation and washed
with distilled water to remove stabilizer residue or any free
drug and lyophilized for storage.

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1. Emulsion-Solvent Evaporation Method:

71
2. Double Emulsion and Evaporation Method:
Emulsion and evaporation method has limitation of
poor entrapment of hydrophilic drugs, Hence to
encapsulate hydrophilic drug the double emulsion
technique is employed.

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Involves:
Addition of aqueous drug solutions to organic polymer
solution under vigorous stirring to form w/o emulsions.
This w/o emulsion is added into second aqueous phase
with continuous stirring to form the w/o/w emulsion.
w/o/w emulsion is subjected to solvent removal by
evaporation and nanoparticles are isolated by
centrifugation at high speed. The formed nanoparticles
must be thoroughly washed before lyophilisation.

73
Variables that affect the characterization of nano
particles:
Amount of hydrophilic drug to be incorporated
Concentration of stabilizer used
Polymer concentration and
Volume of aqueous phase

74

75
3. Salting Out Method:
Salting out based on the separation of a water-miscible
solvent from aqueous solution by salting-out effect.
Polymer and drug are dissolved in solvent and emulsified
into an aqueous gel containing the salting out agent
(electrolytes e. g. MgCl2 & CaCl2, or non- electrolytes such as
sucrose) and a colloidal stabilizer PVP or HEC.
This o/w emulsion is diluted with a water or aqueous solution
to enhance the diffusion of solvent into the aqueous phase,
thus inducing the formation of nanospheres.
Manufacturing variables: Stirring rate, Internal/external
phase ratio, concentration of polymers in the organic phase,
type of electrolyte concentration and type of stabilizer in the
aqueous phase.
Increase of temperature is not required and hence can be
used when heat sensitive substances have to be processed.

76
3. Salting Out Method:

77
4. Emulsions- Diffusion Method:
Encapsulating polymer is dissolved in a partially water-
miscible solvent (e.g. propylene carbonate, benzyl
alcohol) and saturated with water to ensure
thermodynamic equilibrium of both liquids.
Polymer-water saturated solvent phase is emulsified in an
aqueous solution containing stabilizer, leading to solvent
diffusion to the external phase and the formation of
nanospheres or nanocapsules.
Solvent-eliminated by evaporation or filtration, according
to its boiling point.

78
4. Emulsions- Diffusion Method:

79
5. Solvent Displacement / Precipitation Method:
Involves precipitation of a preformed polymer from an
organic solution and the diffusion of organic solvent in
aqueous medium in presence or absence of surfactant.

80
Polymers, drug, and/or lipophilic surfactant are dissolved
in a water miscible solvent (acetone/ethanol).
Solution is then poured or injected into an aqueous
solution containing stabilizer under magnetic stirring.
Nanoparticles are formed instantaneously by the rapid
solvent diffusion.
Solvent is removed from suspensions under reduced
pressure.

81
Rate of addition of the organic phase into the aqueous
phase affect particle size.
As the rate of mixing of the two phases increases,
Both particles size and drug entrapment decreases.
Method is suitable for most of the poorly soluble drugs.

82

83
Applications of Nanoparticles
 Drug Delivery
 Food
 Gene delivery
 Cancer treatment
 Other
 Information & communication technology
 Power engineering
 Industrial engineering
 Environmental engineering
 Chemical industry
 Medicine and
 Cosmetics

84
Characterization of Nanoparticles
1. Size and surface Morphology
2. Specific Surface Area
3. Surface Charge and Electrophoretic Mobility
4. Surface Hydrophobicity
5. Density
6. Molecular weight
7. Drug Entrapment efficiency
8. Kinetic Study
9. Stability of Nanoparticles
10. Drug-Excipient compatibility studies
11. In-vitro Release Studies
12. Phase Behaviour

85
Monoclonal Antibodies
https://www.youtube.com/watch?v=ki-3AOfmAZE

86
Introduction
What Are Antibodies:
Also called immunoglobulins, Y-shaped molecules are
proteins manufactured by the body that help fight against
foreign substances called antibodies.
What Are Antigens:
Substance that stimulates the immune system to
produce antibodies.
Antigens can be bacteria, viruses, or fungi that
cause infection and disease

87
What are Monoclonal Antibodies (MoAb)?
Antibodies that are derived from different cell lines.
They differ in amino acid sequence.
Antibodies that are made by identical immune
cells which are all clones belonging to a unique parent
cell.
Have monovalent affinity, in that they bind to the
same epitope (the part of an antigen that is
recognized by the antibody)
Introduction
What are Polyclonal Antibodies?

History of Development of MoAb
Introduction
1890
1902
1955
1964
1975
1990
Von Behring & kitasato discovered
the serum of vaccinated persons
contained certain substances, termed
antibodies
Paul Ehrlich proposed the “ side-
chain theory” and concept of
Magic Bullets
Jerne postulated natural selection
theory
Porter isolated fragment of antigen
binding (Fab) and fragment crystalline
(Fc) from rabbit y-globulin
Littlefield developed a way to isolate
hybrid cells from 2 parent cell lines
using the hypoxanthine-aminopterin-
thymidine (HAT) selection media
Kohler & Milstein provided the most
outstanding proof of the clonal selection
theory by fusion of normal and
malignant cells
Milstein produced the first
monoclonal antibodies 88

Introduction
Monoclonal antibodies are identical immunoglobulins,
generated from a single B-cell clone.
These antibodies recognize unique epitopes, or
binding sites, on a single antigen.
Derivation from a single B-cell clones and subsequent
targeting of a single epitope differentiates
monoclonal antibodies from polyclonal antibodies.
89

Characters of Monoclonal Antibodies
Monoclonal antibodies (MoAB) are single type of antibody
that are identical and are directed against a specific
epitope (antigen, antigenic determinant) and are
produced by B-cell clones of a single parent or a single
hybridoma cell line.
• A hybridoma cell line is formed by the fusion of one B-
cell lymphocyte with a myeloma cell.
• Some myeloma cell synthesize single mAB antibodies
naturally.
90

Applications of Monoclonal Antibodies
91
(1) Diagnostic Applications
(2) Therapeutic Applications
(3) Protein Purification and
(4) Miscellaneous Applications

92
Pregnancy:
Pregnancy by detecting the urinary levels of human
chorionic gonadotropin.
Cancers:
Estimation of plasma carcinoembryonic antigen in
colorectal cancer, and prostate specific antigen for prostate
cancer.

93
Hormonal disorders:
Analysis of thyroxine, triiodothyronine and
thyroid stimulating hormone for thyroid disorders.
Infectious diseases:
By detecting the circulatory levels of antigens
specific to the infectious agent
e.g. Antigens of herpes simplex virus for diagnosis of
STD .

94
Cardiovascular diseases
Deep vein thrombosis
Atherosclerosis

95
(2) Therapeutic Applications:
(3) Protein Purification:

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