1

2019

Needle Free

Vaccination

Technology

Dr.M.Muruganandam

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Needle Free Vaccination

Technology

Dr.M.Muruganandam

3

First Edition 2019

ISBN 978-9982-22-632-5

Author :Dr.M.Muruganandam

Email:vaccine.m@gmail.com

www.vaccinebiotech.blogspot.com

Publisher

Einsteein Bio-Engineering Research Foundation,

South India.

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Preface

Vaccination saves millions of people from

various diseases. Now advanced methods of

vaccination are discovered, these are pain free and

more effective methods. These are started from

needle free vaccination strategies .Traditionally

needles are used for vaccination; it gives more pain

and gives some other contagious problems. These

methods overcome all the problems and also user

friendly. So children and old age people May happy

to use these pain free methods. In this book, various

methods are discussed one by one .I have taken many

informations from various articles for preparation of

this manuscript. I cordially thank to all authors and

researchers ones again. I thank all of them.

M.Muruganandam

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Content

Chap: 1. Pain Free Vaccination.

1.1 Vaccination.

1.2 Needle Free Vaccination.

Chap: 2. Mucosal Administration

2.1 Mucosal Immunity

2.2 Oral administration

2.3 Edible vaccines

2.4 Eye drops

2.5 Mass Administration

2.6 Intranasal vaccination

Chap:3 Skin Vaccination

3.1 Micro Projection Array and

Nanopatch Technology

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3.2. Nanopatch Device

3.3. American device

3.4. Australian device

3.5. German device

3.6. Cream Vaccination

3.7Spray and Bath Vaccination

Chap:4 Needle Free Injector device

4.1 Jet injector device

4.2 Different types of devices

4.2.1 MGI 500

4.2.2. Recojet

4.2.3. Bioject

4.2.4. Vitajet -3

4.2.5. Cool click

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4.2.6. Serojet

4.2.7. Iject

4.2.8. Intraject device

4.2.9. Biovalve’s Mini-Ject Technology

4.2.10. Antares Medi-Sector vision technology

4.2.11. Auto and pen Injectors

4.2.12. Bioject R ZETAJET

4.2.13. Injex

4.2.14.Advantages

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1. Pain Free Vaccination

1.1 Vaccination

Over 13 million people die from

infectious disease every year in our globe.

Vaccinations have reduced these preventable

infectious diseases from all the time. The Routine

immunization has eradicated small pox from the

globe and leads to the near elimination of wild

polio virus.

In the immunisation method, first needle

injection introduced in the 1850. Then the

intramuscular injection of vaccines has been

used and it was popular delivery method due to

easy to administration. First these technology

has several disadvantages including edible stick

injuries, disease transmission through needle

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reuse (3) limited thermostablity, expertise for

administration, back of targeting to immune rich

regions of the body and tissues of pain that result

in avoidance of medical care in 10% of the

population. Now new technologies required to

overcome challenges in distributing vaccines in

the developing world (4).

1.2 Needle Free Vaccination.

Needle free vaccinations are pain free

vaccination which is given without the use of

needle. There are a number of delivery options for

needle-free vaccinations, ranging from nasal

sprays to patch worn on the skin. The needle free

vaccinations would also be very easy to deliver;

encouraging a wider coverage of the population.

one way to deliver needle free vaccinations is

through mucosal surfaces like the inside of the

nose, mouth and eyes.

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Vaccines could be smeared directly on to

the surface for absorption or they could be

delivered in the form of an aerosol spray oral

vaccines can be delivered in droplets from

directly onto the tongue, as has been done

historically with the oral vaccine for polio drug

companies have also developed jet injectors

which force a liquid vaccine through the pores of

the body. Such injectors do not require a needle,

although they could be momentarily, distressing,

as a jet injector basically punches the skin with a

concentrated spray of liquid.(5).

1.3 Advantages

Needle free vaccination via the skin

offers key advantages in comparison to standard

needle and syringe methods. These include

targeting of Apcs in the skin dermis and

epidermis and enhanced thermostablity through

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dry coating technology and reduced doses per

application, enabling more people to be

vaccinated.(4)

Reference

1.Mabey-D;Peeling,R.W,Ustianowsk;A. and perkins,M.D..(2004)

Nature Rev.Microbial.2. 231-240.

2.Mitragotri.S.(2005) Nat. Rev. Immunal. 5- 905-916.

3.E Kweume. D.V. Weniger. B.G., and chem. R.T. (2002) B. world health

organ 80,859-870.

4.Simon Corrie, Alexandra Depeisenarie, Defeisenarie, and Mark Kendall

(2012) Introducing the Nanopatch: A skin Based needle free delivery system.

Australian Biochemist vol 43 No.3, December 2012.

5.Smitdh (2003 – 2009) wise Geek. (Web.reference) .

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2. Mucosal Vaccination

2.1 Mucosal Immunity

The important future generation

vaccination area is immunization of mucosal

surfaces. Now it should be possible to maximize

the antigenicity of many vaccines and facilitate

their interaction with appropriate lymphoid

tissues to induce protective cellular and humoral

responses. Mucosal vaccines requiring not more

than two doses are achievable with current

technologies.

Live vaccines have been among the

most promising candidates for mucosal

vaccination. Development of new micro

encapsulated delivery system and adjuvant has

made non-living vaccines reasonable options for

mucosal immunization. To be practical, such

vaccines should be developed as combined agent

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vaccines, possibly deliverable by multiple

mucosal routes. Although strategies to be used

for specific mucosal vaccines will depend upon a

number of factors pertinent to be disease agent ,

in concept an adjuvant administrated with

inactivated but maximally antigenic pathogens or

their recombinant adhesive subcomponents could

prove to be among the more practical mucosal

vaccine options for use globally.(1)

The gut mucosal immune system is a

critical component of the body’ defence against

pathogenic organisms especially those

responsible for enteric infections associated with

diarrhoeal disease. Attempts to vaccinate against

infections of mucosal tissue have been less

successful than vaccination against systemic

infections, to a large extent reflecting a still in

complete knowledge about the most efficient

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means for inducing protective local immune

responses at these sites. Secretary IgA (S IgA) is

the predominating immunoglobulin along

mucosal surfaces, and S IgA antibodies

generated in gastro intestinal, respiratory or

genitourinary mucosal tissue can confer

protection against infections affecting

originating in these sites

An efficacious intestinal S IgA immunity-

inducing oral vaccine against cholera has been

developed recently, and development of oral

vaccines against other enteric infections such as

those caused by enterotoxicgenic Escherichia

coli, shigella and rota viruses is in progress as

well.

Based on the concept of a common

mucosal immune system through which

activated lymphocytes from the get can

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disseminate immunity to other mucosal and

glandular tissues, there is currently also much

interest in the possibility of developing oral

vaccines against infections in the respiratory

and urino genital tracts. However, the large and

repeated antigen doses often required to achieve

a protective immune response, therefore, a great

need to develop strategic for enhancing delivery

of antigen to the mucosal immune system as

well as to identify mucosal-active immuno

stimulating agents (adjuvant) .(2).

2.2 Oral Administration

Oral vaccines are safe and easy to

administration and convenient for all ages. They

have been successfully developed to protect

from many infectious diseases acquired through

oral transmission.(3)A polio vaccine was

developed and tested by volunteer vaccinations

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with no formal training; the results were positive

in that the case of the vaccine increased with an

oral vaccine, there is no risk of blood

contamination, oral vaccines are likely to be

solid which have proven to be more stable and

less likely to freeze; this stability reduces the

need for a cold chain, the resources required to

keep vaccines with in a restricted temperature

range from the manufacturing stage to the point

of administration, which in turn, may decrease

costs of vaccines.(4). For travellers, a typhoid

vaccine capsule has been developed as an

alternative to the two painful shorts are typically

required.(5).

2.3 Edible vaccines

Genetic engineering has enabled the

production of oral vaccines in food. In 1998,

potatoes were produced that contained genes

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from the virus. These potatoes showed efficiency

in protecting people from this disease. This is

particularly useful for developing countries.

In the edible vaccine has genetically

engineered protein from an edible material that,

once the genetically altered protein is inserted

into the material and is consumed orally, leads to

the natural production of antibodies against a

certain virus protein, just like any other vaccine.

However, edible vaccines differ from traditional

ones in the way they stimulate the production of

antibodies in the receiver which in the cost of the

edible vaccines, is during digestion.

The protein antigen would interact with

mucous membrane of the gastro intestinal tract,

activating the so-called mucous type of immune

protection. As a result, the organisms would

synthesize antibodies against virus protein

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(Tomato). So the protein antigen is the beginning

stimulator of the body to produce the antibodies

necessary to have a successful vaccine. Edible

vaccines gives benefit to millions of people

every year, Eventually, after many years of

studies and experiments, vaccines could be

created for almost every diseases known to man,

with the creation of edible vaccines, vaccinations

will become available to millions of more

people than can currently get them because of all

these advantages they have very normal

injectable vaccines.

Merits

There are many advantages in edible

vaccine over a general vaccine (injection)

An edible vaccine is less likely spread

infections because no need is needed to

inject the vaccine.

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Another advantages is that the edible

vaccines are much cheaper and don’t

require any special facilities food storage or

transportation.

So depending in the types of food it would

require different types of storage to prevent

the food from going bad, however this

storage is no different from the storage

required for that same type of food that does

not contain the vaccine.

This type of storage is cheap and very

common and easily accessible around the

world.

Especially storage and transportation of the

edible vaccine when compared to the

methods of injectable vaccine.

Need not required trained personnel to

administer for edible vaccines.

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Finally they even taste good.(6)

2.4 Eye drop administration

It is mainly used in poultry industry and also it

is very convenient method. Application of the

vaccine by eye-drop methods is probably the most

effective for live vaccines. It ensures that the

vaccine reaches the individual bird and as a

consequence, titres obtained are usually uniform

throughout the flock, correct dilution of the

vaccine is critical. If eye-droppers are being used,

they should be calibrated before use.

In the absence of suitable eye droppers, it is

also possible to use tip of a feather or a syringe

(Preferably 1ml syringe) to administer the drop.

However, these two options should be seen as last

resorts as they are inaccurate and cause

considerable wastage of vaccine. Eye drop

administration provides good protection because

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the vaccine passes to the Hadrian gland just

behind the eye, which in chickens is a key organ

in the development of the immune response.

2.5. Mass administration

Mass administration of vaccination is mainly

used in various farm animal Industries. In

intensively developed commercial poultry

industries, cost of vaccination is an important so

for this reason, mass application methods have

been developed, primarily for live vaccines.

Various forms of equipment are manufactured to

generate coarse sprays which allow mass

application with minimum adverse reaction,

although in some circumstances, mass application

by fine sprays and aerosols are employed.

In rural areas, it is best to give the drinking

water in the morning just as the chickens are

released from the chicken house. In areas with

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abundant surface water, chickens find their own

source of drinking water .However vaccination

via water is not appropriate.

Vaccination by placing the live vaccine virus

in the drinking water is easier than application to

individual birds, but it provokes a lower level of

immunity than eye – drop administration has left

uniform uptake and requires more frequent

application. The vaccine should be given twice,

initially 2-3 weeks apart, with re-vaccination at

least every three months.

Oral vaccination of chicken with thermos

table vaccines (ie.NDV4 –HR) has been

successful in some developing countries. This

method should be thoroughly tested before being

used widely in the field. The vaccine must be

given more often when administered via feed,

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making it more expensive and survival rates in

the face of an outbreak are lower than those

achieved by eye-drop administration.

Though feed used in any vaccination

campaign should therefore be recommended by

the veterinary Authority. 7kilograms of food per

bird should be well mixed with the

corresponding number of doses of appropriately

diluted vaccine with most grains, 1ml of fluid

will efficiently moist ten grams of grain. The

treated food is best given in the morning as the

birds are leaving the roost. The vaccine should

be given twice, initially 2-3 weeks apart, with re-

vaccination at least every 2-3 months.

2.6. Intranasal Vaccination.

Small pox is the first disease which was people

tried to prevent by purposely inoculating

themselves with other types of infections. Nasal

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vaccination Inoculation is believed to have

started in India or china before 200 B.C.

Physicians in china immunized patients by

picking off pieces from drying pustules of a

person suffering from a mild case of `small pox,

grinding the scales to a powdery substance, and

then inserting the powder in to the person’s noise

in order for them to be immunized.

In 1718, Lady Mary worthey Montague reported

that the Turks have a habit of deliberately

inoculating themselves with fluid taken from

mild cases of small pox.(7) It acted as good

vaccine against small pox. Some vaccines which

protect against respiratory disease such as canine

kennel cough and fline rhintracheitis are

manufactured to be given as drops into nose.

These vaccines generally provide faster

protection than those given intramuscularly or

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subcutaneously. Intranasal vaccines are less

likely to cause allergic reactions and are more

likely to provide protection if maternal

antibodies are still present. In the case of

Bordetella, intranasal vaccines may need to be

given more often than injectable vaccines. The

nasal shot may be the first needle free flu shot. It

is a syringe like device that has an aerosol

sprayer substituted for the needle. It delivers a

weak flu virus directly to the nasal passages and

creates immunity to be flu with minimal side

effects. Inhalers are another type of needle free

delivery systems. In this system, liquids or

powders are inhaled and delivered into the lungs.

These devices are good for delivering protein

drugs because the lungs provide a rapid

absorption into the blood stream. In one system

there is pump unit that atomizes of powdered

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medication. This allows the patient to inhale the

proper amount of medicine without it getting in

the back of the throat. For diabetics who require

daily injections of insulin, an aerosol inhaler has

also been introduced.(5)

Reference

1. Walker. R.J.(1994) New Stratagies for using mucosal

vaccination to achieve more effective immunization vaccine

Apr; 12(5) : 387-400

2. Holmgren (1991) Mucosal immunity and vaccination. Dec. 4;

4(1): 1-9.

3. Qingzhu and Jay.A.Berzo fsky (2012) Large intestine-targeted

nonoperticle –releasing oral vaccine to control genitorectal

viral infection in Natmed vol. 18.pp:1291-1296

4. Vaccines -from Wikipedia

5. Rapolu Bharath kumar (2012) Needle free injection system. The

pharma Innovation vol.1 no;9, pp;57-72

6. Edible vaccine-Net.reference.

7. AAp.publication.org.

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3. Skin Vaccination.

3.1 Micro Projection Array and Nanopatch

Technology.

Micro Projection Arrays (Maps) form is the

part of the push for physical targeting of vaccines

to the skin. The key concept is to fabricate arrays

of micro projections to pierce the tough scalier

and rapidly deliver vaccine payloads to the

epithelia. The first reports on the fabrication and

testing of silicon arrays for trans dermal delivery

appeared in the late 1990s.(1). Since then rapid

expansion of fabrications methods has occurred.

Low density (1-100 projections/cm2) and

medium density (100-5000/cm2) arrays have been

fabricated form silicon, metal, polymer and

ceramic materials, generally in the size range of

0.3-3mm in length .key design parameters include

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the shape, density, length and tip sharpness of the

projections, along with the applications velocity,

as these directly affect the skin penetration depth

achieved by the array. Furthermore, coating

strategies is to optimise formulations for long

term thermostablity rapid release of vaccine pay

load following skin insertion, high release

efficiently and the potential for process scale up.

These methods, along with their

comparative advantages and disadvantages are

reviewed thoroughly elsewhere (2) while pro-

treatment of skin with MPAS followed by topical

vaccine application produced in consistent results,

vaccine-coated MPAS in evoke consistent

immune responses in mice, often exceeding

standard delivery routes. Influenza vaccine

administration has been the most investigated that

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case using coated projections(Maps) showing

protective immunity in comparison with the

needle, on the basis of total Ig G antibody levels,

haemagglutination inhibition titres and

neutralising antibody activity.

The experimental results shows enhanced

immune responses in comparison to intramuscular

injections and dose reduction in which only1/10th

of the dose was required for equivalent Ig G

responses(as measured by ELISA) and term

immune responses even six months after

vaccination The preclinical and clinical trials of

MPA technology has encouraging results to

achieving significant dose reduction (leading to

significant improvements in vaccine distribution

and availability) and significantly improved

thermostablity (3).

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In Nanopatch Technology, Skin nanopatches are

used.They are look like bandages, they slowly

transfer medicine through the skin .In one type of

patch, and thousands of tiny blades are

imbladded on its surface. The patch is covered

with medicine and then placed on the skin. The

blades make microscopic cuts in the skin that

opens a path for drugs to enter though when an

electric current is applied, the medicine is forced

into the body. This process called iontophoresis,

does not hurt.(4)

Generally, the nanopatches are a stamp

sized patch similar to an adhesive bandage

contains about 20000 microscopic projections per

square inch.(5). When worn on the skin, it will

deliver vaccine directly to the skin which has a

higher concentration of immune cells then that in

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the muscles where needles and syringes deliver. It

thus increases the effectiveness of the vaccination

using a lower amount of vaccine used in

traditional syringe delivery system (6).

Scientist designed the Nanopatch, an ultra-

high density MAP with dry-coated vaccine, to

target the dendrite cell populations within the

epithelia with the aim to meet this need. Using

multi-photon microscopy to determine Ape

density in mice, combined with a custom-

designed applicator and Bio- mechanical analyses

of the skin (7)

It was hypothesised that targeted delivery

of vaccine to thousands of Apcs in both the viable

epidermis and dermis-without wide spread cell

death would improve immunogenicity in

comparison to the needle and syringe (8).Deep

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reactive Ion Etching (DRIE) of silicon chips

allowed us to overcome previous limitations and

produce very high density (720,000/cm2) arrays

with short (30-300hm) and sharp projections (9).

In a key proof of concept study, Nano

patches indeed targeted ~50% of available Apcs

in mice (both in the viable epidermis and dermis)

requiring loss then 100 th of the standard

intramuscular dose required for equivalent

protective immune responses using an influenza-

based mouse-model(8).

Delivery of drugs to the skin is only one

potential application of Nanopatch technology.

The collection and processing of whole blood

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prior to immunoassays contribution to the high

cost, complexity, long turnaround time and

expertise required to perform diagnostic tests for

diseases.

Rapid screening in infectious disease is a

key concern and in the future rapid screening to

aid personalised treatment of complex diseases

(eg; cancer, diabetes, and cardiovascular disease)

is likely to benefit from advances in this area. The

skin is highly vascularised with a blood vessel

density ranging form20-40 vessels/mm2 at a depth

of 58-65mm (8). Further experiments help to

explore more applications of the Nanopatch by

investigating arrange of different vaccines,

developing novel coating technologies and

formulations to support long term thermostablity.

Using a novel jet –coating approach the

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nanopatch technology has been used to deliver a

range of different vaccines including inactivated

whole virus vaccine (8) virus like particles (eg;

Gardasil – Commercially available tetravalent

human Papilloma virus vaccine).(10) DNA plasmid

(11)and other compositions, using the same jet

coating procedure.

In the case of fluvax, only ~100th of a

standard intramuscular case delivered via the

nanopatch was required to produce equivalent

protective immune responses as determined by

total IgG measured by ELISA and

haemagglutination inhibition assays. more

recently researchers demonstrated that co-

delivering fluvax with the adjuvant quil Ain a

mouse model improved this level of dose

reduction form 100 fold to 900 fold(12). scientist

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also demonstrated long –term thermostablity of

our dry coated Nanopatch vaccines, showing

comparative immunogeneicity with freshly coated

devices or those coated and stored for over six

months at 23.c prior to skin applications.(13)

3.2 Nanopatch Device

The Nanopatch device is solid silicon

sputter- coated with a 100mm thin layer of gold

and measures 5mmx5mm in size. The centre

4mmx4mm area contains 3364 density of

individual projections that are 30µm at the back

and between 65 and110mm in length Nano

patches are dry-coated with antigen, adjuvant and

/or DNA pay loads. The coated Nanopatch was

applied to the skin at 2.0/m/s for 10 minutes after

Nano patch removal, the coating that was on the

micro projections appear to have remained in the

skin as expected.

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The high density of the projections

significantly increases the probability of targeting

vaccine directly to the skin immune cells in

available epidermis and/or dermis within a given

surface area of skin. When the patch is placed

against the skin, these projections push through

the outer skin layer and deliver the biomolecule to

the target cells when dry, the vaccine formulation

is stable and strong, when the Nanopatch is

applied to the skin the projections immediately

become wet, with the vaccine dissolving within

minutes.

Being both painless and needle free the nanopatch

offers hope for those with needle phobia as well

as improving the vaccination experience for

young children. The Australian Scientist team is

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currently in the process of designing a nanopatch

to match the special arrangement of APC in

human skin. Prof. .Kendall says now we have

proven the nanopatch in the animal model. The

next step is to translate successfully to clinical

studies using the nanopatch to vaccinate

people.(15)

3.3 American patch device

A needle free patch is developed for

vaccination by Intercell USA with the help from

design giant Ideo.The new vaccination system

which uses a patch, is known in scientist-speak as

transcutaneous immunization, and its secret is the

langerhans cell, part of the immune system that is

in the skin. Inter cell discovered how to trigger an

immune response from the Langerhans cells, and

then asked Ideo to help. In this group, they have

recently introduced the micro patch which based

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on a similar MAP concept is designed to

selectively capture blood borne disease bio-

markers form the skin for applications in rapid

diagnostics,(18,19).design a product for vaccine

delivery. But there was a stumbling block from

the outset; an extremely thin layer of skin needs

to be removed just before applying the patch.

The layer is about one 1000th of an inch or

25 microns thick, explain Tad Simons the projects

leader in ideo’s health practice. Ideo’s designers

tried hundreds of skin-prep techniques on their in

house test subjects, aka themselves, some days

they appeared ‘ covered with road rash polka dots

says simons.They finally settled on a device

equipped with a strip of find sand paper.

By pressing it on to the skin and pulling a

39

tab with a motion skin to removing a port-it tape

flag them is package. The sand paper rubs the

skin at the right speed and the right pressure.

Simons says, there is no perception on the skin of

happening .Because the scratch is invisible, the

device leaves an in market to orient the placement

of the vaccine patch.

Intercell expects the first patch vaccine to

target traveller’s diarrhoea. That product, which

could generate more than 750 million year in

revenue is moving towards FAD approval phase 2

trials are done and phase 3 testing is set for early

2009. A second vaccine for endemic flu is in the

pipeline. Inter cells ambitions are even bigger; it

hopes the technology will be used for vaccination

campaigns with kits simply mailed out for self

application.(14)

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3.4 Australasian Nanopatch Device

Australian Scientists have developed a

cheap and painless needle- free vaccination

device that can be self-administered. A team of 20

researchers led by professor mark Kendall form

Australian Institute for Bio- engineering and

Nanotechnology at the university of Queensland

have developed Nanopatch, a stamp- sized

vaccine delivery device that could make

vaccination programmes globally simple and

cheaper. The nanopatch having 20,000 micro

projects per square centimetre, is designed to

directly place vaccine in to the human skin which

is rich in immune cells and unlike the needle and

syringe which place vaccines into the muscle-

which has very few immune cells then Nanopatch

puts it to our immure sweet spot and by doing that

are make vaccines work a lot better said by

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Kendall.

Kendall also said, The Nanopatch potential

lies in it being cheap, painless, very effective

being transported without refrigeration and can be

given without the need for extensive training. The

removal of the need for refrigeration is achieved

by dry coating vaccine to the Nanopatch which

could have huge potential for developing

countries like India and many with in Africa.

The world Health organization estimates 50

percent of vaccines in Africa do not work

properly because the ‘cold chain’ has been

broken. In a pandemic the reduced dose would

also make it easier for government to supply

sufficient vaccine to the public. The new device is

simple as it does not need a trained practitioner to

administer the vaccine. The Nanopatch has to be

42

worn to just 2 minutes or even less thus giving a

pain – free immunization. Kendall said, the

vaccine could hit market in next 10 years.(

3.5 Germen Device

The Berlin-based company capsulation

Nano science has signed a Co-operative contract

with the Twebingen-based biotechnology

company EMC micro collections GmbH and

charite- universitats medizin Berlin. The aim of

this three year long co-operation is the

development of the topical vaccine, vaccines

which by simple application to the surface of the

skin can be used to treat cancer or to prevent

infectious diseases Taking part in the co-

operative project sponsored by the federal

ministry of Education and research with a

million Uros is also the Institute for cell Biology

at the university of Tubingen.

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The basis of the vaccine used in the

needle free non-invasive method is the unique

and mutually corresponding developments of

the partners involved. Thus the composition of

the basic components in the synthetic vaccines

could already be clarified in successful

preliminary work undertaken by the Department

of Immunology in the Dermatology clinic at the

charity together with the university of Tubingen

and EMC micro collections GmbH.

The Department of skin physiology

of the charite is production the findings for the

optimum penetrations of the substance through

the skin where as capsulation Nanosciences-AG

qualifying their functional listed nanoparticles as

carrier systems for vaccines. In order to reach

44

our common goal we need to adjust the

immunologically active components to the

specific requirements of the skins immune

system explains CEO, professor Karl Hein

Weissmuller form EMC micro collections

GmbH. At the same time suitable forms of

application need to be developed. In particular,

the transport particles need to be modified to the

size rations within the hair follicles. For this

testing nanoparticles defined sizes between

400mm and1000mm adds capsulations project

manager Lars Dahre. The task in hand is to reach

only as far down as the hair follicles.

The skin layers underneath however and

the sebaceous glands should not be touched.

After all only above the sebaceous glands can be

empty particles be excreted by the natural

45

cleaning mechanism of the skin. In the hair

follicles the vaccine particles are confronted with

dense net of immune cells. The residing

Langerhans cells and dendrite cells of the in

herent immune systems incorporate the released

vaccine components and present them to the

immune system.

It is critical according to Daphne that the

amount of released vaccine per particle and time

unit is enough to attain optimum sensitization

capsulations --LBL Technology delivers. The

promising solution approach here. The minimal

vaccine developed by Emc micro collections and

the charite consists of only three substance

groups absolutely necessary for a successful

immunisation. The first, a cocktail various well

known antigens frequents activate cytotoxic cells

46

against. a certain pathogen while the two other

groups induce the general response to the

immunity. The groups, which differ greatly in

their physical chemical properties form one

another need to be thus antagonise against the

particle, so that they release themselves

simultaneously in the hair follicle the so called

PH. shift.

This is one part of the task that we want to

undertake using the LBL Technology says

Dahre. After all none of the components should

be missing at this particular point. with the new

vaccinations method complications such as

inflammation pain or allergic reactions in

comparison with common vaccination methods,

can be avoided.

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In the developing countries in particular

where the multi use of one time syringes is not un

common it can stop the spread through standard

intramuscular vaccination of infectious diseases

high as HIV and hepatitis. In this country, small

children particularly would profit from the pain

free method.(16)

3.6 cream vaccination

One of the previous experiments shows

skin cream vaccine development work. In that

work, first plasmid DNA of bacterial pathogen

was prepared and appropriate amount of other

skin cream components are mixed during

preparation. Now cream vaccine is ready to use.

The skin cream is prepared by using bee wax

with coconut oil. The plasmid DNA vaccine is

dissolved in double distilled water and mixed

well during preparation.

48

It was applied on the surface of ear skin of

Albino rats at three times with 24 hours interval.

After 24 hours of vaccination blood samples were

collected and analysed .The while blood cells

count were increased in vaccinated group

compared to control group. This is the indication

of function. So based on this preliminary study, it

is concluded that skin cream vaccine is also

confirmed as one of the good pain free vaccine

delivery system. In future it gives new scope for

help to mass vaccination programme in children

and all age group people.

3.7 spray and Bath vaccination

These methods are mainly followed by fish

culture industry. It is another modification of

direct immersion of fish. However in this method

the fish would need to be handled making the

49

process stressful. During bath vaccination fishes

immersed 20 minutes to several hours. The

vaccine can be added directly to hatchery or

transport bags.

In the both vaccination, vaccine was

dissolve in water 1;10 range than used

Appropriate numbers of fish were introduced in

vaccinated water. Under constant aeration, These

novel vaccine provides significantly higher

protection after bath challenges compared with

commercial vaccine.(21).

Bibliographic Reference

1.Henry, S, mcallister, D.v.,Allen, M.G.and prausnitz, M.R.(1998).

Jpharm. sci ,87 922-925.

2.Kim,y,c, park.J. H. and prausnit.z,M.R(2012). Adv. Drug. Deliv

Rev in press

3 Simon corrie, Alexandra Depelsenarie and mark kendall, (2012)

Introducing the Nanopatch A skin based Needle free vaccine

delivery system, australion Biochemist. vol.43,No.3.pp 17-20

4.Rapolu Bharath kumar (2012) .Needlefree Injection systems, The

pharma Innovation vol.1.No.9 pp;57-72

50

5.Austrailan scientist develops needle free vaccination. The

Hindu.28. sep.2011

6.Needle free Nanopatch vaccine delivery system. News

medical.3.Aug. 2011

7.crichton.M.L., Ansaldo, A, chen x, prow T.W, Fernando. G.J.. and

kendall, M.A(2010) Biomaterials, 31,4562-4572.

8.Fernando. G.J., chen x., prow, T.w, etal (2010) plos one,5,elo266.

9.Jenkins. D.,corrie,s, Flaim.c. and kendall M.A.F.(2012) RscAdv.2.

3490-3495

10.corbelt, H.j, Fernando, G.J., chen ,x, Frazer I.H., and Kendall

.M.A.(2010). plos. one,5,e 13460.

11.chen. x, Kask, A.S, crichton, M.L, etal, (2010).J.control release

1498,327-333.

12.Fernando. G.J. Hcten, x, primiero, C.A. etal (2012).J. control

Release, 159, 215-221

13.chen .x, Fernando, G,J cricntion M.L et al, (2011).J. control

Release 152, 349-355.

14.Tim Mckeough (2008) Inter cell’s Needle free vaccines. Fast

company magazine Nov. 2008.

15.Michael Berger (2010) Needle- free painless vaccinations with

nanopatches. – anowork (web- reference)

16. Needle- free Vaccines pressebox. com march-2008.(web-referce)

17.K.N. mohanta and .S.K.majhi.(2003) On Fish vaccination.

Fishing chimes. vol.23.no.7 pp; 39-41.

18.Huzaiar,m, m. Riuis, F, Rajad byaks ha.m. et al, (2001). J. In vest

51

Dermatal.116, 846-852.

19. muller ,D.A, corrie, S,R, coffey, J, young, P.R. and kendall,

M.A. (2012) anal.ctem. 84,3262-3268 20.Corrie,S.R., Fernando,G.J,

crichton, M.L, Brunk, M.E.., AndersonC.D.,and

kendail,M.A.,(2010). Lab chip 10,2655-2658.

21.Bakopoulous.V., D . Volpathi, L , Gusmani m. Galeotti, A

Adeums and G.J. Dimitriadis (2003) vaccination trials of seabass,

Dicentrarchus labrax(L). aganist photbacterium damsela sub sp.

piscicida, using novel vaccine mixtures.J.fish.Dis.26,77-90

52

4. Needle Free Injector devices

4.1 Injector Device

The principles which are the basis of the

use of the drugs to penetrate the skin whether

the drug is in solid and liquid or in powder

form have been established for many years

needle free injection technology offers effective

injectors for a wide range of drugs and bio-

equivalent to needles and syringes. Needle free

device have demonstrated consistent delivery to

the epidermis, the dermis, the subcutaneous and

the intramuscular space.

They offer less pain, avoid needle

stick injuries and contamination allows self

administration and results in no needle phobia

and thus strongly preferred by the patients.

Some of them are ideally suited to chronic

53

injections of varying doses of insulin proteins

and monoclonal antibodies (1).

Needle free injection system has

potential to improve effectiveness. Major

advantages of needle free systems are the

elimination of broken needles, a more constant

delivery of vaccines and drugs and decreased

workers safety risk. Needles free injection

systems are customizable to each operation and

can be modified to optimize productivity.

However, implementing a needle free system

can be challenging. Workers require training

and education regarding any new technique. (2)

4.2. Different Types of the Devices

Now different types of needle free

injection devices are developed. They are mainly

used to vaccine delivery and other drug delivery

54

functions without pain. They are discussed one

by one

4.2.1 MHI 500(1)

Mhi-500 is the novel needles free

insulin delivery system which offers benefits for

all these involved in diabetes care and also for

these involved in the management of clinical

waste. It is a real alternative to needle based

delivery systems. Compared with needle

injection system, the mhi-500’s needle- free

insulin delivery technology improves the

dispersion of the insulin throughout the tissue.

This technology achieved the food

and drug administration (FDA) approval in 1996

for the subcutaneous delivery of insulin and is

CE marked for sale throughout the Europe. This

system has been used to give thousands of

55

successful injections without the use of a needle.

The mhi-500 injects insulin by using a fine, high

pressure jet for insulin. This jet then penetrates

the tissue, depositing the insulin in the

subcutaneous layer. The jet is created by forcing

the insulin precisely designed nozzle that is held

in contact with the tissue during the injection.

2.2Recojet

Shreya life sciences have recently

launched its recombinant human insulin under the

brand name Recosulin and a needle free insulin

delivery device, Recojet. According to the

company sources, Recojet is India’s first needle

free insulin delivery device and poised to

revolutionise the insulin therapy. The new device

is expected to give boosts to the therapy, as needle

phobia was one of the reasons preventing insulin

use on a wider scale. In general needle free

56

injection technology works by forcing liquid

medication at high speed through a tiny orifice

that is held against the skin. This creates an ultra-

fire stream of high pressure fluid that penetrates

the skin without the use of a needle.

2.3. Bio ject’s needle free injection Technology

Bio ject’s needle free injection

technology works by forcing liquid medication at

high speed through a tiny orifice that is held

against the skin. The diameter of the orifice is

smaller than the diameter of human hair. This

creates an ultra fine stream of high pressure fluid

that penetrates the skin without using a needle.

Bio ject’s technology is unique

because it delivers injections to a number of

injection depths and supports a wide range of

injection volumes. For instance, the Biojector

57

2000 can deliver intramuscular or subcutaneous

injections up to one ml in volume. In addition,

Bio-ject is developing a syringe for the Bio-jector-

2000 that delivers intradermal injections that is

currently in clinical trials. Bio ject has a portfolio

of needle free injection products to meet the

varied needs of today’s health care environment.

Each product is unique in its power source.

The Bio jector 2000 is a durable

professional grade injection system designed for

health care providers. The Bio jector 2000 is the

only needle free system in the world cleared by

the FDA to deliver intramuscular injections. The

system can also deliver subcutaneous injections

and is being used for intradermal injections in

clinical trials. The Bio jector 2000 used sterile

single use syringes for individual injections,

58

which present the cross contamination that has

been reported with fixed nozzle ject injection

systems. More than 10 million injections have

been administered successfully using the

Biojector 2000, with no reports of major

complications. Because there is no needle, the Bio

jector provider health care workers with an

unparalleled level of protection against accidental

needle stick injuries. In risk situations, such as

delivering injections to patients known to be

infected with HIV, hepatitis, the Bio jector is an

ideal injection system.(1)

4.2.4. Vitajet -3.

The vitajet -3 is an easy to use,

economical needle free injection system for

delivering insulin. This system requires no

maintance or re- assembly, with disposable

nozzles that are replaced once a week the vita jet

59

-3 offers the quality of usable medical product

with the convenience and safety of a sterile

disposable.

The exclusive, easy to read crystal

check disposable transparent nozzle allows

inspecting the dosage prior to injection and

visually confirming loading and full discharge of

insulin after each use. The vita jet-3 received the

FDA marketing clearance for delivering

subcutaneous injections of insulin in 1996. Since

then, the system has been used to deliver

hundreds of thousands of injections, safely,

economically and without the use of a needle (1).

4.2.5. Cool Click

Bio ject developed the cool click

needle free injection system for delivering

recombinant human growth hormone. In some

children, naturally occurring growth hormone is

60

absent or is produced in inadequate amounts. In

these cases, seize or growth hormone

replacement must be injected to maintain normal

growth.

Cool click is a customized version

of Bio ject’s vita jet-3 needle free injection

system. The system includes customized

dosage features to accurately deliver variable

doses of saizen and was designed with bright

colours to make the injector attractive and non-

threatening to children. The cool click received

FDA market clearance for delivering

subcutaneous injections of saizen in June

2000.(1)

4.2.6. Serojet

The Serojet is a needle free

injection system for delivering serostim

recombinant human growth hormone for

61

treatment of HIV- associated wasting in adults.

HIV – associated wasting is a metabolic

condition in which people infected with HIV

lose body weight. If not treated, this could

result in increased morbidity and mortality.

Serono- developed serostim to treat

this condition by utilizing the natural properties

of growth hormone in increasing lean body

mass. Serojet is a customized version of Bio

jects vitajet needle free injection system. The

system includes customized dosage features to a

accurately deliver FDA market clearance for

delivering subcutaneous injection of serostim in

march 2001.(1)

2.7. Iject

Bio ject has developed a second

generation gas powered injector known as the

62

Iject Which is based on the design and

performance of B 2000 and is intended to service

as a single use pre-filled device. The pressure

profile of the Iject has been documented by

testing to be virtually the same as that of the

2000 and injection performance of the two

devices is therefore predicted to be equivalent.

The Iject is a pre- filled single use

disposable injection device configured to

administer 0.5 to 100 ml. Subcutaneous or

intramuscular injections. The device is

distributed ready to use. Thus it requires no

additional parts or modifications for function.

The device is primed by rotating the trigger slave

180 degrees and an injection is administered by

advancing the trigger slave while the nozzle is

held against the injection site. The Inject needle

63

free injection system is an investigational device,

subject to the US Food and Drug administration

Clarence for commercial distribution (1).

Aradigm corporation has been recently

acquired the Intra ject technology, initially

developed in the UK by Weston medical. It is

the only pre-filled and disposable needle free

device in late stage development with

commercial scale up in process. Aradigm’s intra

ject collaborators include roche for the delivery

of pegylated interferon alpha (pegasys) and

Glaxo Smith Kline for imitrex. The Intraject

device is about the size of a fountain pen. The

drug capsule is glass a material that has

demonstrated excellent stability profiles for

liquid protein formulations.

The energy to drive the actuator

64

forward to deliver the 0.5ml. Formulation is

provided by compressed nitrogen. The delivery

process is completed in less than 60 mille-

seconds with less bruising and discomfort than

may be encountered with syringes pens or other

devices.(1)

4.2.9.. Bio value’s Mini ject technology

The mini ject represents the next

generation in needle free injection systems by

combining the features of accuracy reliability, a

variety of pre-filled options comfortable

administration and full disposability all within a

patient friendly easy to use design. The mini-ject

can deliver a wide range of drug, ranging from

small molecules to large proteins, fragile

antibodies and vaccines.

Delivery can be target to intradermal,

65

subcutaneous or intra muscular depending on the

clinical need. No other single use needle free

delivery technology provides the same level of

performance as the mini ject technology with the

ability to target specific tissue layers over such a

broad range of drug volumes (0.1ml to 1.3ml) and

viscusities.(1)

4.2.10. Antares Medi- jector vision Technology

Antares pharma, one of the

Pioneers in the field of needle free injection

technology has developed med- jector vision

technology which is use to deliver insulin to

diabetes suffers. It is a newest marketed dose

spring the reusable variable dose, spring

powered device for insulin delivery.

This technology is also being used

to deliver human growth hormone. Its plastic,

disposable needle free syringe allows the patient

66

to see the dose prior to injection. It is marked in

U.S. and Europe for insulin administration since

1999.

4.2.11. Needle free auto and pen injectors

An auto injector is a medical

device designed to deliver a single dose of

particular drug (typically life setting) Most auto

injectors are spring loaded syringes. By design,

auto injectors are easy to use and are intended

for self administration by patients or

administration by untrained personal. The site

of injection depends on the drug loaded but it

typically is administered into the thigh or the

buttocks. The injectors were initially designed

to overcome the hesitation associated with self

administration of the needle based drug

delivery devices. (3)

Advances in auto injector design

67

and in needle free injections are helping

pharmaceutical companies to market their

drugs and to complete more effectively by

providing gains in market share, allowing

greater penetration of markets, helping patients

to comply with dosage regimes and providing

safer injections. Indeed, injection devices were

once considered as an after rough but now in

some product categories they are becoming an

entry ticket; and essential part of the drug’s

presentation to the market, without which they

would fail to attract patients.

Pharmaceutical companies are

developing injections in parallel with their new

drugs, in the knowledge that a device will be

needed at product launch. Auto-injectors are

advancing both commercially and technically

with recent launch of a second pre- filled single

68

use device, containing a standard pre- filled

syringe, which automates needle ingestion,

drug delivery and automatically covers the

needle after use.

Drugs are use to treat Anaemia

and Netropenia. They are newly available in

which pre- filled convenient patient friendly

presentations. In parallel to auto injector

development there have been significant

advances in needle free and powder delivery

which are increasingly showing that they offer

can alternative to the needle. (4)

4.2.12. Bio ject RZETAJET (6)

The Bio ject zeta jet, Bio ject’s latest

advance in needle free delivery system, consists

of two components the portable injector and an

auto disabling disposable syringe. It is intended

to deliver vaccines and injectable medications

69

either subcutaneously or intra muscularly and is

indicated for both professional use and home use

for patients who self- inject. The syringe

assembly has a unique auto disable features that

prevents reuse of the syringe. The Bio ject Zeta

jet has FDA clearance for delivering

subcutaneous or intra muscular injections of

liquid medication including vaccines and other

injected medications.

4.2.13. Injex

It is a needle free injections for infiltration

an aesthesia – Injex pharma now offers a

solution for previous local anaesthesia problems,

a needle free injection system.

The Injex system uses an injection

ampoule with a micro orifice of only 0.18 mm

through which the aesthetic is administrate under

dosed pressure to the sub mucus virtually

70

painless and exactly where it is needed.

MDAJETXL PODIATRY NEEDLE FREE

INJECTOR (7)

Easy to use and virtually painless

compared to needles provides instant local an

anaesthesia or regional blocking for most

podiatric procedures. Minimizes tissue trauma

and facilitates suturing as there is no tissue

distension around the injection site. Provides

adequate anaesthesia for deep needle insertion,

may used with anaesthetics, steroids and other

medicanents, has inter changeable extend tips for

easy sterilization between patients can be used

on all age groups.

Consistent depth of penetration of 4-5.5

mm below the epithelium and makes a wheel at

the base of the injection of 5-6 mm in diameter,

Consistent volume of 0.1 cc per injection

71

intradermaly. Permits approximately 38

injections with single loading ( to 4.cc) may be

sterilized by auto- cleaving or your usual

sterilization process – do not use dry heat.

4.2.14. Advantages

Needle phobia needle sticks injuries and Conta

minations may be avoided. Patient care self

administered Injectable emergency situations are

important Public health issues where needle free

devices can bring significant improvements. In

improving patients health better comfort of

administration better acceptance of heavy chronic

treatments and consequently better treatments

compliance.

.

In eliminating needle stick injuries and

associated contamination and the consequent

dramatic social, psychological and economical

72

coseqences.In allowing – in emergency

situations quick, efficient and non – traumatizing

injections. In avoiding the risks and the costs

associated to the elimination of contaminated

sharps In avoidant the risk and the costs

associated to the elimination of contaminated

sharps

In offering the pharmaceutical and biotech

companies unique opportunity of differentiation

in a context of life cycle management of their

products and patients can easily administer their

treatment chronically and form home or at work

if needed. The Medical staffs have the guranty of

safe and quick delivery of the right treatment at

the right dose in the right place. Pharmaceutical

companies offer patients and practitioners a

unique and convenient way to administering

their products and a way to differentiate.

73

Disposal of sharp medical waste requires costly

sharps disposal service. Pharma ject needle free

syringe can be disposed in the same way of used

Band- Aid is disposed – thus making it simple

and in expensive. (8,9.)Many of these needle free

alternative technologies are in the development

stage companies are still working on producing

devices that are safer and easier to use.

Bibliographic Reference

1. Pharma Tutor- Needle free injection Technology – page -3. (

Net reference )

2.Rapolku Bharath Kumar (2012) Needle free injection

system . the pharma Innovation vol .1. No.9. PP-57 -72

3.http; ll en. Wikipedlia .org\wiki \ pen injector.

4.http ll network . nature . com\hubs\ London \ events \

951ttp; ll

5. www. \smp.org \ Newsletters/ acute care \articles \ 20061\\

Bn. Asp.

6.http; ll www. Bioject. Com \ products \ zetajet.

7. http; ll www. Buffalo hospital. com \ files\ documents \ w

sets – needles syringe. Pdf.

74

8.American nurses association ; 2008 study of nurses views

on work place safety and needle stick Injuries summer 2008.

9. World health organization (Gives) global immunization

vision and strategy 2006-2115; oct. 2005, page;44.

.

75

About the Author

Dr.M.Muruganandam is an Editor of

African journal of Biotechnology and International

journal of Medicine and Biomedical Research. He is

also Reviewer and Editorial board member in

Various National and International journals. He

published more than hundred publication including

ten books.