VACCINE DRUG

DELIVERY SYSTEM
PRESENTED BY,
SREESHNA T S
M.PHARM FIRST YEAR,
DEPARTMENT OF PHARMACEUTICS,
MADRAS MEDICAL COLLEGE.

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VACCINE

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CONTENTS:
• INTRODUCTION
• TYPES OF VACCINES
• DELIVERY SYSTEMS FOR VACCINE
• UPTAKE OF ANTIGENS
• SINGLE SHOT VACCINES
• MUCOSAL VACCINE DELIVERY SYSTEM
• TRANSDERMAL VACCINE DELIVERY SYSTEM
• REFERENCE

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INTRODUCTION
• Vaccine is a material that induces an immunologically mediated
resistance to a disease but not necessarily an infection.
• Vaccines are generally composed of killed or attenuated organisms or
subunits of organism or DNA encoding antigenic proteins of
pathogens.
• The term VACCINE applies to all biological preparation produced by
living organisms, that enhance immunity against disease and either
prevent or treat disease.

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VACCINATION

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VACCINATION:
Vaccination is the most efficacious and valuable tool in prevention
of infectious disease, provided that they are administered
prophylactically in anticipation of pathogen exposure.
The goal of vaccination is to stimulate a strong protective and
long lasting immune response to the administered antigen.

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PROPERTIES OF AN IDEAL VACCINE:

• Give lifelong immunity.

• Prevent disease transmission.
• Rapidly induce immunity.
• Stable, cheap and safe.
• Effective in all subjects( the old and very young).
• Transmit maternal protection to the foetus.

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ROUTES OF ADMINISTRATION:

• Deep subcutaneous or intra muscular route (most vaccines).

• Oral route ( oral BCG vaccine).
• Intradermal route (BCG vaccine).
• Intranasal route ( live attenuated influenza vaccine).
• Scarification ( small pox vaccine).

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COMPOSITION OF VACCINE
• Vaccines consist of:
• BULK ANTIGEN + OTHER FLUIDS(water or saline) +
PRESERVATIVES + ADJUVANTS.
• These ensure the quality and potency of the vaccine over its shelf life.
• Vaccines are always formulated as to be safe and immunogenic when
injected to humans.
• It is formulated as liquids, but may be as freeze-dried for
reconstitution immediately prior to time of injectio n.

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STEPS INVOLVED IN VACCINE
ACTION
When inactivated or weakened disease causing microorganism enters
the body.

They initiate an immune response.

This response mimics the body’s natural response to infection.

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WORKING OF VACCINE

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CLASSIFICATION OF
VACCINE

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1.TRADITIONAL VACCINE:
• Killed vaccine
• Live attenuated vaccine
• Toxoid
• Subunit vaccine
2.INNOVATIVE VACCINE:
• Conjugate vaccine
• Recombinant vector vaccine
• T- cell receptor peptide vaccine
• Valence
• Heterotypic
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TRADITIONAL VACCINES:
• Killed – The killed but previously virulent, microorganism that have
been destroyed with chemicals, heat, radioactivity or antibiotics.
Eg: influenza, cholera, polio.
• Live, attenuated – some vaccine contain live, attenuated
microorganism. Some of the active viruses that have been cultivated
under condition that disable their virulent properties to produce a
broad immune response.
Eg: yellow fever, measles.

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• Toxoid- made from inactivated toxic compound that cause illness
rather than the microorganism.
The toxins are inactivated by treating them with formalin. Such
detoxified toxins are called toxoids.
Eg: Tetanus and Diphtheria.

• Subunit – It is a protein subunit, a fragment of it can create an

immune response.
Instead of the entire microbe, subunit vaccines include only the
antigens that stimulate the immune system.
Eg: Plague immunization

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INNOVATIVE VACCINE:

• Conjugate vaccine- certain bacteria have polysaccharide outer coats that

are poorly immunogenic. By linking the outer coats to the protein, the
immune system can led to recognise the antigen.
Eg: Haemophilus influenza type B vaccine.

• Recombinant vector vaccine- by combing the physiology of the

microorganism and the DNA of the other, immunity can be created
against the disease.
Eg: DPT
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• Valence-
 Monovalent: use to immunize against single antigen.
 Multivalent: use to immunize against two or more microorganism.

• Heterotypic- Vaccines that are pathogens of other animals that do not

cause disease.
Eg: BCG vaccine made from mycobacterium bovis to protect against
tuberculosis.

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DELIVERY SYSTEMS FOR
VACCINE

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DELIVERY SYSTEM FOR
VACCINE:
NEEDLE VACCINE DELIVERY SYSTEM
• Intramuscular
• Subcutaneous
• Intradermal
NEEDLE FREE VACCINE DELIVERY SYSTEM
• Nasal drug delivery
• Topical drug delivery
• Oral drug delivery

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NEEDLE VACCINE DELIVERY
SYSTEM

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NEEDLE VACCINE DELIVERY
• INTRAMUSCULAR :
Administration of vaccine into the muscle mass.
Eg: Rabies, DPT
• SUBCUTANEOUS:
Administration of vaccine above the muscle just below the skin.
Eg: MMR, Yellow fever.
• INTRADERMAL:
Administration of vaccine in the topmost layer of the skin.
Eg: BCG vaccine.
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NEEDLE FREE VACCINE DRUG
DELIVERY

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NEEDLE FREE VACCINE DRUG
DELIVERY
NASAL DRUG DRLIVERY SYSTEM:

• It has a ability to induce mucosal IgA that provides a local defensive

mechanism against the pathogen entering the body through the
mucosal surface.
• It is successfully done by aerosols because of safe, effective, -
immunogenic, economical, easy to administer.
• Eg: Flu vaccine

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TOPICAL DRUG DELIVERY SYSTEM:

• It is the simple, painless and economical approach to vaccination.

• It is a novel method by which the antigens and adjuvants are applied
topically to intact skin to induce potent antibody and cell mediated
responses.
• They are categorised as:
Physical- iontophoresis, gene gun, laser pulse, ultra sound waves
Chemical-permeation enhancer Eg. Azones, DMSO

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ORAL DRUG DELIVERY SYSTEM:

• Oral vaccine drug delivery system is one of the easiest method to

administer the vaccine.
• Eg: Polio vaccine

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UPTAKE OF ANTIGENS

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UPTAKE OF ANTIGENS
• ANTIGENS:
The components of the disease-causing organisms or the vaccine
components that trigger the immune response are known as
ANTIGEN.
• ANTIBODIES:
These antigens trigger the production of antibodies by the immune
system. Antibodies bind to corresponding antigens and induce their
destruction by other immune cells.

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STEPS INVOLVED:

• The induced immune response to either a disease-causing organism or

to a vaccine configures the body’s immune cells to be capable of
quickly recognizing, reacting to, and subduing the relevant disease
causing organism.

When the body’s immune system is subsequently exposed to a same

disease-causing organism, the immune system will contain and
eliminate the infection before it can cause harm to the body.

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Stages of exogeneous antigen
uptake:
UPTAKE
Access of native antigens and pathogens to intracellular pathways of
degradation
DEGRADATION
Limited proteolysis of antigens to peptides
ANTIGEN-MHC COMPLEX FORMATION
Loading of peptides onto MHC II molecules
ANTIGEN PRESENTATION
Transport and expression of peptide-MHC complexes on the surface of cells
for recognition by T cells
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Stages of endogeneous antigen
uptake:
UPTAKE
Antigens/pathogens already present in cell
DEGRADATION
Antigens synthesised in the cytoplasm undergo limited proteolytic degradation
in the cytoplasm.
ANTIGEN-MHC COMPLEX FORMATION
Loading of peptide antigens onto MHC molecules
PRESENTATION
Transport and expression of antigen-MHC complexes on the surface of cells
for recognition by T cells
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SINGLE SHOT VACCINE

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SINGLE SHOT VACCINE
Single dose vaccines are given at a single contact point for preventing
4 to 6diseases.
In order to increase the therapeutic efficiency of such vaccines, adjuvants
are used.
E.g: DTP (Diphtheria-Tetanus-Pertussis), MMR (Measles-Mumps-
Rubella).
ADVANTAGES:
• They would replace the need for a prime boost regimen,
consequently eliminating the repeated visits to the doctors.
DISADVANTAGES:
• Costly
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VACCINE ADJUVANTS:
• Adjuvants are the substances added to vaccines to help them work
better.
• Adding an adjuvant triggers the immune system to become more
sensitive to the vaccine.

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Role of adjuvants in vaccine development:

1. Increase the therapeutic efficiency.

2. Decrease the dose of antigen.
3. Enhance responses in the young or old.
4. Increase the speed and duration of the response.
5. Induce potent cell-mediated immunity.
6. Enable successful vaccine development.

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Biodegradable polymer as adjuvants:

• Biodegradable polymers such as Poly (lactide-co-glycolic acids) is

most commonly used for vaccine delivery.

This polymer is mainly responsible for:

 Controlled release of the vaccine from polymer matrix.

 Targeting to appropriate cell types to generate optimum response.

Development of formulation that can be used as non-invasive.

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Microspheres

• Biodegradable polymeric particles have been shown effective for the

development of single dose vaccines and have been applied to the
development of active targeting delivery systems.

• Microspheres are defined as solid, spherical particles ranging in size 1-

1000 um, made up of polymeric, waxy or protective materials.

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Preparation of Microspheres
Microspheres are prepared by various methods like:
 Double emulsion method
 Polymerisation
 Phase separation and coacervation
 Spray drying
But, the most suitable method for the vaccine microspheres is the
DOUBLE EMULSION method.

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Double emulsion method

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ADVANTAGES OF MICROSPHERES:

• Sustained and controlled release

• Detoxification
• Prevention of instability to environment
• To enhance the immunogenicity of weaker immunogens
• To improve the efficacy of the vaccines in individuals having
weakened immune response.

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MUCOSAL VACCINE DELIVERY
SYSTEM

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MUCOSAL VACCINE DELIVERY
SYSTEM
• Mucosal surface area is major portal of entry for many human
pathogens that are the cause of infectious disease worldwide.
• Immunization by mucosal routes may be more effective at inducing
protective immunity against mucosal pathogens at their site of entry.
• Discovery of safe and effective mucosal adjuvants are also being
sought to enhance the magnitude and quality of the protective immune
response.
• It is estimated that 70% of infectious agents enter the host by mucosal
routes.

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DESIGN AND STRATERGIES FOR MUCOSAL DELIVERY:

• EMULSION TYPE DELIVERY

• LIPOSOME BASED DELIVERY
• POLYMERIC NANO PARTICLES
• VIROSOMES
• MELT IN MOUTH STRIPS

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Emulsion Type Delivery
• Emulsions are heterogeneous liquid systems may be water-in-oil
emulsions(w/o) , oil in water emulsions(o/w), or more complex
systems such as water in oil in water (w/o/w) multiple emulsions,
micro emulsions, or nano emulsions.
• Antigens are dissolved in a water phase and emulsified in the oil in the
presence of an appropriate emulsifier.
• The controlled release characteristics of an emulsion are determined
by factors such as
Viscosity of oil phase
Oil to water phase ratio
Emulsion droplet size
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 Eg: High oil content – injection site irritation.
Too large droplet size – physically unstable product.

ADVANTAGES:
• Slow release of antigen.

DISADVANTAGES:
• Access immunogenic response
• Fever
• Sore arm at injection site.

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Liposome Based Delivery
• Liposomes are spherical shape vesicles containing an aqueous core
which is enclosed by a lipid bilayer.

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PREPARATION OF LIPOSOME VACCINE DELIVERY SYSTEM
Depending on the chemical properties, water soluble antigens
(proteins, peptides, nucleic acids, carbohydrates, haptens) are entrapped
within the aqueous inner space of liposomes.

Lipophilic compounds ( lipopeptides, antigens, adjuvants, linker

molecules) are intercalated into the lipid bilayer).

Antigens or adjuvants can be attached to the liposome surface either

by adsorption or stable chemical linking.

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ADVANTAGES:
• Easy surface modification.
• Plasticity
• Synthesized from non toxic material.
• Wide range of antigen encapsulation.

DISADVANTAGES:
• Stability problem.
• Low antigen loading.

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Polymeric Nanoparticles
• Polymeric nanoparticles are submicron sized colloidal particles.
• Polymeric nanoparticles because of their size are preferentially taken
up by the mucosa associated lymphoid tissue.
• Limited doses of antigen are sufficient to induce effective
immunization.
• Hence, the use of nanoparticles for oral delivery of antigens is suitable
because of their ability to release proteins and to protect them from
enzymatic degradation in the gut.

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• Biodegradable Poly Methyl Metha Acrylate (PMMA) nanoparticles
being very slowly degradable ( 30% - 40% per year) appears to be
particularly suitable for vaccine purpose because prolonged contact
between antigen and immunocompetent cells favours persistent
immunity.

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ADVANTAGES:
• Release antigen at target site.
• Surface properties can be easily tailored for better immunogenecity.

DISADVANTAGES:
• Insufficient antigen protection.
• Premature (burst) release.

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Virosomes
• A virosome is a drug or vaccine delivery mechanism consisting of
unilamellar phospholipid membrane ~ 150 mm (either mono or
bilayer) vesicle incorporating virus derived proteins to allow the
virosomes to fuse with target cells.
• These proteins enable the virosome membranes to fuse with cells of
the immune system and thus deliver the specific antigens directly to
their target cells.
• They elicit a specific immune response even with weak immunogenic
antigens.

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• Once they have delivered the antigens, the virosomes are completely
degraded within the cells.
• Virosomes represent vesicular systems into which antigens can be
loaded into virosomes or adsorbed onto the virosomal surface through
hydrophobic interactions.

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ADVANTAGES:
• Virosomes are biodegradable, biocompatible and non toxic.
• There is no risk of disease transmission.
• No auto immunogenecity or anaphylaxis.
• It is broadly applicable to all important drugs ( anticancer, antibiotics,
fungicides, proteins).
• Capable of delivering the drug into the cytoplasm of the target.

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Melt in Mouth Strips
• Quick dissolving films containing immunogens.
• Melts into liquid that children and infants will swallow easily.

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• First designed by undergraduate students at Johns Hopkins University
on biomedical engineering deisgn day for protection against rota virus
infection.
• Rotavirus is a common cause of severe diarrhoea and vomiting in
children, leading to about 6,00,000 deaths annually.

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• Rotavirus vaccine at present is available in a liquid or freeze dried
form that must be chilled for transport and storage, making it very
expensive for use in impoverished areas.
• In addition, newborns sometimes spit out the liquid, a problem that is
less likely to occur with a strip that sticks to and dissolves on the
tongue in less than a minute.

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TRANSDERMAL DELIVERY OF
VACCINES

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TRANSDERMAL DELIVERY OF
VACCINES
• Transdermal delivery is one of the needle free method of vaccine
delivery.
• Transdermal delivery targets the vaccine to the skin, thereby
promoting its contact and potentially reduce the required dose of
vaccine.
It has the potential to
Reduce the risk of needle borne disease.
Improve access to vaccination by simplified procedures.

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Approaches

The various approaches are:

LIQUID JET INJECTION
EPIDERMAL POWDER IMMUNIZATION
TOPICAL APPLICATION.

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LIQUID JET INJECTION
Needle Free Injection Devices:
• Liquid jet injectors use A HIGH- VELOCITY JET (typically 100 to
200 m/s) to deliver molecules through the skin into the subcutaneous
or intramuscular region.
• Jet injectors can be broadly divided into Multi-use nozzle jet
injectors (MUNJIs) and Disposable cartridge jet injectors (DCJIs),
depending on the number of injections carried out with a single
device.
• Liquid jet injectors consists of a power source (compressed gas or
spring), piston, vaccine- loaded compartment and an application
nozzle (orifice size in the range of 150 to 300 µm)

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• Upon actuation the power source pushes the piston rapidly increases
the pressure within the vaccine loaded compartment, thereby forcing
the drug solution through the orifice as a high velocity liquid jet.
• When the jet impacts on the skin it create a hole through allowing the
liquid to enter the skin.
• The process of hole formation and liquid jet deposition occurs within
microseconds.
• The deposited liquid can then disperse within the tissues to illicit an
immune response.

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ADVANTAGES:
• Increase immune responses when compared to conventional vaccine.
• Dose sparing
• Increases the speed
• Avoids risks and discomfort.
DISADVANTAGES:
• Variable reactions including pain and bruising at the site of
administration.

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EPIDERMAL POWDER
IMMUNIZATION
• Powder injectors has been investigated for transdermal protein
delivery, gene therapy and vaccination.
• The device design principles are similar to liquid injectors, with a
powder compartment and compressed carrier gas such as Helium.
• Upon actuation, the particles are carried by the gas, to impact the skin
surface at high velocity, puncturing micron-sized holes in the
epidermis to facilitate skin deposition.
• Humoral and cell mediated immune response following vaccination
with jet propelled particles has been demonstrated in clinical studies.

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ADVANTAGES:
• Powder injectors offer advantages over liquids in terms of formulation
and stability issues.
• Initial safety studies suggest that the powder injectors are reasonably
well tolerated.

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TOPICAL APPLICATION

Topical applications range from non-invasive formulation based

approaches (e.g. Colloidal carriers), energy based approaches
(ultrasound or sonophoresis, and electroporation), and minimally
invasive approaches (such as microneedles)

• Topical adjuvants:
Topical administration of the vaccine with adjuvants, has been shown
to induce strong systemic and mucosal immune responses.
The adjuvant activates the Langerhans cells in the skin thus priming
the immune response to the co-administered vaccine 67
1.COLLOIDAL CARRIERS:

The rationale for the use of colloidal carriers is that compounds with
unfavourable permeation characteristics can be packaged within
carriers that will permeate the skin.

While there has been considerable research in the application of

liposomes and lipid particle carriers, there is no conclusive evidence
that these carriers can permeate the skin intact.

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Nano particles and Nano carriers:
Nanoparticles and microparticles are polymeric particles in the nanometre and
micrometre size range respectively.

Vaccines can be incorporated into the particles in form of a solid dispersion or

a solid solution, or bound to the particle surface by physical adsorption and
chemical binding, thus allowing the particles to act as carriers or as adjuvants
for the vaccine.

While there have been sporadic reports of nanoparticle based skin delivery, the
general consensus is that nanoparticles administered to the skin do not
permeate the intact stratum corneum, but may accumulate in hair
follicles.

 Consequently their potential utility for passive Transdermal vaccine delivery

is limited. 69
2.ENERGY BASED APPROACHES:

• Exposure of skin to energy in form of electrical pulses or ultrasonic

waves increases the permeability of the skin.

A)ELECTROPORATION:

• It involves the administration of electrical pulses to create transient

pores in the skin and thus increases the skin permeability to vaccines.
• Eg: Delivery of DNA vaccines involves electroporation.

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B )SONOPHORESIS:
Ultrasound or sonophoresis:
• Application of ultraviolet waves at frequencies between 20 to 100
kHz to the skin surface increases the skin permeability.
• Eg. Tetanus toxoid.

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C) MICRONEEDLES:
• It consist of pointed micro sized projections fabricated into arrays upto
hundred needles to penetrate the skin surface thereby allow the
vaccine delivery.
• It is made of titanium or silicone.
• There are several approaches for the delivery of vaccines by the
microneedles namely:
Poke and patch method
Coat and poke method
Poke and release method
Poke and flow method
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Poke and patch method:

• The microneedle permeabilize the skin by forming micro sized holes

through the stratum corneum.
• Then the microneedle array is removed and then the vaccine
containing patch is applied.
• This approach is termed as poke and patch method.

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Coat and poke method:

• Solid microneedles are coated with dry powder in the skin.

• Coated microneedles have an insoluble core coated with dry powder
vaccine that dissolves off within the skin.
• This approach is termed as “coat & poke”.

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Poke and release method:

• Polymer microneedles contain the vaccine in a solid solution of needle

that dissolves, swells or degrades on skin insertion, then releases the
vaccine
• This approach is termed as “poke & release”.

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Poke and flow method:

• Hollow microneedles through which the vaccine solution can be

infused into the skin.
• Insoluble hollow microneedles create holes through which the vaccine
solution can pass into the skin
• This approach is termed as “poke & flow”.

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REFERENCE

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REFERENCES:

1.Controlled and Novel drug delivery by N.K.Jain.pg.no: 147- 164.

2. A Review on Transdermal delivery of vaccines by A.K.M Salman
Haque.
3.Recent trends in vaccine delivery system: A review by CH Saroja, PK
Lakshmi, Shyamala Bhaskaran -International Journal of Pharmaceutical
Investigation | April 2011 | Vol 1 | Issue 2.
4. Vaccine delivery system by Ms. Janu Vashi (slideshare).

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5. A Review on vaccine delivery systems by Singh Mahesh, Dwivedi
Deepti, Pandey Shubham and Verma Monika.
6. Transdermal delivery of vaccines by Sarika Namjoshi and Heather
A.E. Benson – Research gate.
7. http://www.vaccines.gov/more_info/types/

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THANK YOU

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