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1
2019
Needle Free
Vaccination
Technology
Dr.M.Muruganandam
2
Needle Free Vaccination
Technology
Dr.M.Muruganandam
3
First Edition 2019
ISBN 978-9982-22-632-5
Author :Dr.M.Muruganandam
Email:[email protected]
www.vaccinebiotech.blogspot.com
Publisher
Einsteein Bio-Engineering Research Foundation,
South India.
4
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
5
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
6
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
7
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
8
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
9
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.
10
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
11
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) .
12
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
13
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
14
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
15
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
16
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
17
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
18
(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.
19
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.
20
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
21
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
22
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,
23
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
24
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
25
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
26
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.
27
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
28
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
29
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).
30
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
31
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
32
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
33
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
34
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
35
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.
36
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
37
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
38
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)
40
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
41
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.
43
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.
47
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.