4. It can be defined as solid or hollow cannula
with an insertion length of approximately 20-
1500 microns and external diameter not more
than 30 micron.
MICRONEEDLE TECHNOLOGY uses devices
consisting of hundreds or even thousands of
tiny microscale needles that are arranged in a
orderly array of rows and columns
4
Ruturaj Anant Deosthali
5. 1st Microneedles were reported by Albert
Pisano(1993) & Ken Wise (1994)
In 1998,a team led by Mark R. Prausnitz and Mark
G. Allen produced microneedle that struck out of
the plane.
The original application of microneedles in
biomedicine were concentrated on drug delivery.
Currently,the applications of microneedles are
expanded beyond their representative biomedical
applications comprising disease long term
treatment ,immunological administration ,disease
diagnosis & cosmetic field.
5Ruturaj Anant Deosthali
8. 1.Solid Microneedles: Three types
-Silicon
-Metal
-Polymer
Used as pretreatment for pore formation in
order make holes through which drugs can
tranport.
Increased permeability by pocking the holes in
skin,rub drug over area or coat needle with
drug.
8Ruturaj Anant Deosthali
9. Coated microneedle pierce the skin surface
and also carry drugs across the membrance.
Coating solution contains
-Drug
-Excipients(thickening
agent,Surfactants,Stabilizers etc)
-Coating Solution
9Ruturaj Anant Deosthali
11. Lumen diameter 30 microns & height
250microns
Carry drug continuously into the body by
diffusion.
Large amount of drug are delivered
Remove fluid from the body for analysis.
11Ruturaj Anant Deosthali
13. Large molecules can be administered
Painless administration of active pharma
ingredient
First pass metabolism is avoided
Faster healing at injection site
No fear of needle
Specific skin area can targeted
Rapid drug delivery
Decreased microbial penetration as compare
with a hypodermic needle,microneedle
punctures only the eoidermis
13Ruturaj Anant Deosthali
14. Repetitive injection may collapse the veins
The external environment like hydration of
the skin
The tip of microneedle may break off and
remain within the skin on removal of patch
14Ruturaj Anant Deosthali
16. Skin is not only a potent barrier, but also
helpful for delivering bioactive agents. Thus
it is well applied in molecular diagnosis and
treatment. Microneedles were usually
introduced for disease treatment by
enhancing penetration and transporting
drugs . At present the application of
microneedles is undergoing expansion to
more fields including immunobiological
administration,disease diagnosis and
cosmetic use.
Drug Delivery
16Ruturaj Anant Deosthali
17. It was beginning of 19th century that methods
of enhancing the skin transport for
transdermal delivery attracted an enormous
amount of inserts to perform extensive
research. As is known,transdermal drug
diffusion across the skin is faced with great
challenge due to strong barrier, the intact
stratumcorneum
Transdermal delivery possesses many
advantages as compare to the intramuscular
injection, subcutaneous injection, intradermal
injection.
17Ruturaj Anant Deosthali
18. Cellular Delivery;
It can be used to deliver membrane
impermeable molecules into cells.
Local Delivery
Targeted delivery help to reduce side
effects, minimize the dose & helps deliver drug
to locations difficult to treat.
Systemic Delivery
Helps overcoming limitations of
conventional injections.
18Ruturaj Anant Deosthali
19. In order to improve the skin permeability , different
techniques have been developed and employed such
as using permeation enhancer either chemical or
physical.
Following sections gives an overview of enhancing
techniques.
1.Microneedles in combination with
Iontophoresis
This technique of transdermal iontophoresis involves
the application of a physiologically acceptable low
electric current to skin and works on the principle of
”like repels like” in order to promote the transfer of
charged and polar substances across the stratum
corneum of the skin. 19Ruturaj Anant Deosthali
20. 2. Microneedles in combination with
Sonophoresis
Sonophoresis involves application of ultrasound
causing perturbation of lipid bilayer inducing change
in lipid arrangement of stratum corneum results
enhancing the transportation of drugs across the skin.
Here the drug penetration can be controlled by
controlling the frequency of ultrasound.
3.Microneedles in combination with
Electroporation
Electroporation involves the application of high
voltage for shot duration (milliseconds) current
(generally 50-1000 V/cm) causing a transitory ,
20Ruturaj Anant Deosthali
21. localise perturbation of lipid bilayer inducing
structural rearrangement of the cell membrane due
to the electric field.
4. Microneedle in combination with
Vibratory actuation
Precise control of insertion force is required for the
penetration of a microneedle into the skin and it
should not exceed the fracture force of the
microneedle.
Vibration causes tissue damage some times occurs
hence it is necessary to reduce the force insertion.
21Ruturaj Anant Deosthali
22. 5.Microneedles in combination with
Vesicles
Several studies have been performed and reported on
the employing lipid vesicles for the transdermal drug
delivery.
However this system are surrounded with controversy
related to their delivery mechanism which is reported
to be associated with the accumulation of the vesicle
and encapsulated drug in stratum corneum to penetrate
the skin.
6.Microneedles in combination with
Microparticle & Nanoparticles
Penetration of drug particle is depends on their size
and shape of the particles, material properties.
This combination causes increase in cellular uptake can
achieve by decreased particle size. 22Ruturaj Anant Deosthali
23. 7.Microneedles in combination with
Micro pump
Conjunction of microneedles with micro pumps
provide precise delivery of drug as pumps control the
flow rate & pressure for delivery of concentrated drug
solution.
23Ruturaj Anant Deosthali
24. In recent years, cosmetic combined with
microneedle treatment has made a great progress.
The fact that a large number of cosmetical
products were manufactured proved that cosmetic
application is promising. In general, cosmetic
applications are mainly devided into two parts.
1. Promote the natural healing of injured skin
2. To enhance skin permeation of cosmeceuticals
24Ruturaj Anant Deosthali
25. In addition, microneedles can transport active
cosmetic molecules into skin directly for improving
effectiveness and safety, creating microchannels
without reaching nerve.
This can be devided into two broad categories
1. Patches
2. Rollers
25Ruturaj Anant Deosthali
26. Generally alpha-
hydroxy acid such as
glycolic acid(GA) and
Lactic Acid(LA)are
used in cosmetic
patches.
The important fact in
cosmetic patches is
its suitable & peel
properties.
26Ruturaj Anant Deosthali
27. This is applicable
for decrease
puffiness &
under eye circles
and minimize the
look of fine lines.
The microneedles
can range
between 0.5mm
to 3mm in length
which is rolled
over on the skin
surface for 10 to
15 min once in
week 27Ruturaj Anant Deosthali
28. The used of can also be employed in field of
diagnosis.
Hollow microneedles along with quantum dots help in
medical diagnosis
Hollow microneedles can puncture the skin into the
epidermis to withdraw SIF by capillary force or using
vaccum. The extracted SIF metabolised were applied
to diagnose several diseases like cancer, thrombosis,
cardiovascular disorder and diabetes.
Quantum dots are nano scale crystals with a light
emitting property
The multiphoton microscopy method could rapidly
diagnose cancer or other medical problems.
28Ruturaj Anant Deosthali
29. Recent research focuses on the development of
magnetic nanoparticles along with magnetic
microneedle tips those safely collect biomarkers that
indicate early-stage osteoarthritis in knees , hips and
other joints.
Work has been carried out on development of two
sensing device based on hybrid microneedles array for
diagnostic as well as therapeutic applications
Hybrid microneedles having a porous structure were
prepared which can include a variety of biological
molecules as drugs.
Here the First device is an electrochemical sensor
where microneedles contain enzymes in their matrix
that interaction with glucose. The redox reaction with
glucose mediated by ferrocene , create a charge
transfer resulting incurrent proportion to glucose
concentration. 29Ruturaj Anant Deosthali
30. The second device is therapeutic tool with optically
controlled released of drug.
Microneedle have also been developed as sensor for
hydrogen peroxide , lactate , dissolved oxygen and
glutamate.
The microneedle have been employed as bioelectrical
interfaces, especially for neural recording and
stimulation as well as electroencephalography (EEG)
measurements.
30Ruturaj Anant Deosthali
31. The conventional routes to deliver vaccines or
antibodies are administered by hypodermic injection
,intramuscular injection or intradermal injection for
preventive inoculation.
Attributing to drawbacks of conventional vaccination
procedure of needle phobia and the pain associated
with insertion of needle into the skin, recent studies
have focused on development of needle free
vaccination like liquid jet injectors, powder injectors,
thermal ablation and microneedles for the
administration of immunological via Subcutaneous,
Intramuscular or Intradermal route for the prevention
of infectious diseases.
31Ruturaj Anant Deosthali
32. Microneedles have edge over the other methods due
to lack of pain, self-administration and quick
delivery of vaccine.
Making use of microneedles allows vaccines to cross
the stratum corneum and stimulate a clinical
response.
In case of dissolving microneedles, controlled and
complete penetration is an important parameter to
be considered. These are capable of delivering a
small dose less than several miligrams of peptides,
proteins, vaccines, harmones and organic
compounds
Numerous studies have been performed and
reported on vaccine delivery using microneedles
including;
-human IgG
-tetanus toxoid 32Ruturaj Anant Deosthali
34. Phlebotomy refers to the withdrawal of blood samples for
analysis of specific blood constituents for diagnosis of a
disease.
Blood samples are generally collected from capillaries by
priking the skin or from veins using evacuated collection
tube,depending on the volume of blood required for
analysis.
This methods are associated with disadvantages such as
excessive bleeding , infection , scarring , fainting or
feeling light-headed.
People may hesitate to give blood due to fear of needles
and the moderate the pain associated with the procedure.
In such case, painless blood sampling using microneedles
can be very good alternative.
34Ruturaj Anant Deosthali
35. Microneedles situated at a distance of 500 to 2000mm
in the dermis layer beneath the skin can be used to
obtained precise body fluids as well as blood samples
from the capillaries.
Apart from making the painless procedure , it also
reduces blood sample requirements (up to 200
nanolitres).
However the most essential requirement is that the
microneedle must penetrate to sufficient depth hence
care should be taken in the design , material selection
and dimensions of the microneedle ,to ensure
penetration at low pressure without breakage.
Painless Hollow microneedle-based micro sampling
can be used instead of traditional method for glucose
estimation in case of disease diabetes.
35Ruturaj Anant Deosthali
36. Microneedles can also be used for monitoring of
therapeutic drug level.
36Ruturaj Anant Deosthali
37. Thus it was concluded that microneedles are more
efficient as compared to hypodermic needles and the
other conventional delivery system.
37Ruturaj Anant Deosthali
38. Brand Name Manufactured by Application
BD Soluvia Becton Dickinson, USA Intradermal delivery of
drugs and vaccines
MicroCor Corium International
Inc,USA
Administration of drug
including monoclonal
antibodies
MicronJet Nanopass Inc,Israel Delivery of Small as
well as large
molecules of protein
,peptides , vaccines
38Ruturaj Anant Deosthali
39. Date of Filling Applicant Key Invention Country
16/04/2007 Nemaura
Pharma Ltd
Applicator for
Microneedles
USA
12/12/2012 3M
Innovative
Properties
Company
Assembly of
microneedle adhesive
patch include backing,an
adhesive and matrix
coupled to the backing
USA
02/11/2011 Singapore Invention related to
plastic microneedle
strips used in TDD for
increasing DD rate
through skin.
Spain
39Ruturaj Anant Deosthali
40. 1.Comprehsive molecular characterization of
microneedling therapy in a human 3D skin
Model
Here use of microneedles on 3D skin model.
-The skin model resulting in almost complete
recovery of epidermis 5 days after treatment.
-Micro array analysis identify an up regulation
of Gene's that are associated tissue remodeling
& would healing ,epithelial proliferation
,immune cell recruitment.
40Ruturaj Anant Deosthali
41. -On other hand we detected a down
regulatory of pro-inflammatory cytokines and
antimicrobial peptides.
41Ruturaj Anant Deosthali
42. The calculation results showed that the
expansion caused by the infusion of
microneedles stops and flow rate drops to
zero in short time.
The experimental results of jet infusion
through a single needle in silica rubber and
poly acrylamide gel agree with calculation
results qualitatively.
42Ruturaj Anant Deosthali
43. Various research studies carried out on
microneedles are evident enough to state that
microneedle are the efficient and potential
transdermal delivery system.
They have been gaining a lot of importance due
to their key advantages including safety,
convenient, & painless.
Numerous studies have been performed &
reported on the synergist effect of combining
microneedles with other techniques for
enhancing drug delivery such as sonophoresis,
electroporation, iontophoresis vibratoy etc.
43Ruturaj Anant Deosthali
44. Review paper on “Microneedle Technology; A new drug
delivery system” by Nahida Tabassum, Aasim Sofi,Tahir
Khuroo,International Journal of Research in Pharmaceutical
and Biomedical science, Vol 2 , Issue 1,2011
Review article on “Microneedle for Transdermal Drug delivery
by Mark Prausnitz , Advance Drug Delivery Review , Vol 56 ,
Issue on 5,2010.
Langer R (1998) Drug Delivery and Targeting Nature 392(6679)
(Suppl);5-10.
Ruturaj Anant Deosthali 44