This presentation includes the recent fivE year patentS as well as research articles mainly on dissolving needles and further description on typesof mns,mechanism of drug release,etc

1. MICRONEEDLES IN TRANSDERMAL DRUG
DELIVERY
3/5/2019 1
GUIDED BY :
PROFESSOR
HETAL THAKKAR

2. OUTLINE
 DEFINATION
 NEED OF HOUR
 TYPES OF MICRONEEDLES
 APPROACHES OF DRUG DELIVERY
 MANUFACTURING TERCHNIQUES
 NOVEL FABRICATION
 MATERIAL OF CONSTRUCTION
 ADVANTAGES AND DISADVANTAGES
 MARKETED PRODUCTS
 RESEARCH PAPER DISCUSSION
 PATENTS APPROVED
 ADVANCEMENTS
 CONCLUSION
 REFERENCES
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3. DEFINATION
 They are micron scale needles arranged on transdermal
patch providing painless, noninvasive needles considered
third generation TDDS . They are Typically 100s of micron
long,1-50 um wide at the tip, and approximately 50-300 um
at the base.
 According to FDA, products that penetrates beyond the
stratum corneum into living layers of the skin meet the
medical device defination. device’s following attributes will
also be considered
 Needle length
 Arrangement and sharpness
 Degree of control (wrt to penetration)
 NOTE:NOT ALL MICRONEEDLING DEVICES FALL UNDER THIS DEFINATION.EG
THOSE DEVICE WHICH DONOT PENETRATE THE LIVING SKIN
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4. 3/5/2019 4
Source: sixing et al

5. 3/5/2019 5

6. 3/5/2019 6

7. NEED OF MICRONEEDLES
 Delivering drug with minimal discomfort
ensuring best patient compliance
 painless and irritation free delivery
 Simple and self administrable
 Provides proper drug loading.
 Suitable for high molecular wt drugs
 Provides direct entry of drug through the
skin layers.
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8. Types of microneedles
 Based on drug delivery
 Based on polymer interaction
 Based on transportation method
 Based on fabrication/structure
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9. Based on
drug delivery
 Solid
removable
MN
 Coated MN
 Dissolving MN
 Hollow MN
 Hydrogel
forming MN
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Source: research
gatehttps://www.google.com/url?sa=i&source=images&cd=&cad=rja
&uact=8&ved=2ahUKEwjn2Y3F99XfAhVbiHAKHWnsC4IQjRx6BAg
BEAU&url=https%3A%2F%2Fwww.sciencedirect.com%2Fscience%
2Farticle%2Fpii%2FS0168365917310556&psig=AOvVaw1lI_Bod-
MqEEn9WPcJgWbS&ust=1546753387336391

10. continued
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11. Continued..
3/5/2019 11

12. Solid MNS
 Create holes in Sc and are applied before application
of medicine and removed thereafter .
 Increase the permeability by pocking the holes in skin
,rub the drug over area or coat needle with drugs
 Fabricated in 750-1000um in length
 Material used
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POLYMER FEATURES LIMITATION
SILICON BRITTLE ,MAY
BREAK INSKIN
COSTLY
METAL GOOD
MECHANICAL
STRENGTH,LOWC
OST
EG SS, Ni ,Fe
Fabrication

13. TYPES OF COATING
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Dip coating
Gas jet drying
Spray drying
EHDA (electrohydrodynamic atomisation) PROCESSES
Piezoelectric inkjet Printing.
COATED MICRONEEDLES
https://www.google.com/url?sa=i&source=images&cd=&ved=2ahUKEwiHysXM_9XfAhVDinAKHYvGAJoQjRx6BAgBEAQ&url=%2Furl%3Fsa%3Di%26
source%3Dimages%26cd%3D%26ved%3D%26url%3Dhttps%253A%252F%252Fwww.mdpi.com%252F1999-
4923%252F7%252F4%252F486%252Fpdf%26psig%3DAOvVaw1hCHJFjSOT4xRPKZ19QhE_%26ust%3D1546755268754658&psig=AOvVaw1hCHJ
FjSOT4xRPKZ19QhE_&ust=1546755268754658

14. DISSOLVING MICRONEEDLE
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https://www.nanowerk.com/nanotechnology_articles/id47367_1l.jpg
Mechanisms of direct access to draining lymph nodes through “albumin hitchhiking approach” upon a
rapid dispersion of amphiphilic vaccines (amph-vaccines) released by a simple application of dissolving
microneedles (MNs). After 5 min application of dissolving MNs into a dermis layer of the skin which is
highly perfused with lymphatic capillary networks, released amph-vaccines from dissolving MNs bind
and complex to endogenous albumin, and efficiently drain into draining lymph nodes, lead to enhanced

15. ADVANTAGES OF DISSOLVING
MNS
 NO BIOHAZARDOUS WASTES PRODUCED.
 The pedestal part of microneedle arrays is also made of the
water-soluble polymer so that it can easily be eliminated by
dissolving in water.
 Removes the risk of accidental needle-stick injury or intentional
reuse of needles, which is common in some developing
countries and is responsible for INFECTIOUS DISEASES.
 The microneedle arrays delivery enhances the immune
response through inflammatory cues and targeted delivery of
antigen and adjuvant to the high density of antigen-presenting
cells in lymph node.
 Better patient compliance.
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16. HOLLOW MICRONEEDLE
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b ) Drawing lithography
was performed to
fabricate a bevel-angled
hollow microneedle: a)
SU-8 photoresist was
spin-coated onto a glass
panel, b) a 3-
dimensional solid mold
was obtained by drawing
lithography, c) nickel
was electroplated on the
solid mold, d) a bevel
angle was introduced at
the tip of the metallic
microneedle by laser
cutting, e) a bevel-
angled hollow metallic
microneedle remained
upon removal of the
solid mold
Source publication

17. CONTINUED..
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Schematic representation of a hollow microneedle for minimally invasive
blood extraction. ( a ) Skin structure and use of an optimized microneedle for
blood extraction

18. Hydrogel forming MNS
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19. 3/5/2019 19
Source : pubs.rsc.org
BASED ON POLYMER INTERACTION

20. BASED ON STRUCTURE
 IN PLANE -Parallel to substrate surface
 OUT PLANE –Protrude out of substrate
surface .
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21. BASED ON
TRANSPORTATION METHOD
 POKE AND PATCH
 POKE AND RELEASE
 POKE AND FLOW
 COAT AND POKE
 DIP AND SCRATCH
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22. CONTINUED..
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23. MANUFACTURING OF MNS
 LASER CUTTING
 MEMS TECHNOLOGY
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24. Laser cutting
 Using infrared laser we can cut stainless steel
sheets.
 The desired mn shape and dimension are drafted
in AUTOCAD software.
 USING THIS DESIGN LASER ENERGY IS
USED TO CUT THE MICRO NEEDLES
 Cutting speed:2mm/s
 Air purge at constant pressure 140kpa
 Either inplane or outplane fabricated.
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25. MEMS technology
 Deposition of thin films of material on
substrate
 Patterning
 etching
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26. 3/5/2019 26

27. Material of construction
MATERIAL OF
CONSTRUCTIONS
EXAMPLES TYPE OF MN
PRODUCED
MERITS
GLASS -------- HOLLOW High drug
loading
capacity
METAL Nickel-iron 11, stainless steel 12 ,
titanium 13
Hollow/solid/ coated Greater
mechanical
strength
SILICON SILICON DIOXIDE SOLID/HOLLOW Greater
mechanical
strength , High
drug loading
POLYSACCARIDES carboxymethylcellulose 20 ,
Amylopectin 20, Maltose 21, Dextran
22, Galactose 22, Chondroitin Sulfate
22 , Thermoplastic starch 23
SOLID
/DISSOLVING
Rapid drug
delivery,
biodegradable
BIODEGRADABLE
POLYMERS
Polylactic acid 15, Polyglycolic acid
15 , Polylactide-co-glycolic acid
(PLGA) 15, polycarbonate16 ,
Polyvinylpyrrolidone (PVP)
SOLID Cost effective,
good
resistance,bioc
ompatible
NONBIODEGRADABLE
POLYMERS
Polyvinyl acetate (PVA) 18, Alginic
acid 18, Gantrez AN-139, a
copolymer of methylvinylether and
maleic anhydride (PMVE/MA) 18,
Carbopol 971 P-NF 18, Polyetherimide
SOLID Cost effective,
good
resistance
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27

28. ADVANTAGES
 rapid onset of action
 painless administration of the active pharmaceutical ingredient
 Large molecules can be administered
 first-pass metabolism is avoided
 faster healing at injection site than with a hypodermic needle
 patient compliance due to ease of administration
 decreased microbial penetration as compared with a hypodermic
needle
 the microneedle bypasses the stratum corneum and punctures only the
epidermis
 specific skin area can be targeted for desired drug delivery
 Drug can be administered at constant rate for a longer period
 good reproducibility
 good stability and enhanced drug efficacy may result in dose reduction
 good tolerability without long-term oedema or erythema
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29. DISADVANTAGES
 skin irritation may result because of allergy or sensitive skin
 local inflammation may result if the concentration of drug is
high under the skin
 careful use of the device may be needed to avoid particles
‘bouncing off’ the skin surface;
 if the device is not held vertically, the dose may escape or can
penetrate the skin to differing degrees
 the thickness of the stratum corneum and other skin layers
varies between individuals and so penetration depth of particles
could vary too external environment, like hydration of the skin,
could affect delivery tip of the microneedle may break off and
remain within the skin on removal of the patch
 Compressed dermal tissue can block hollow microneedles
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30. Patents granted in last
few years
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31. 3/5/2019 31

32. 3/5/2019 32

33. REMOTE RESERVOIR MICRONEEDLE DRUG DELIVERY
SYSTEMS
Pub. No.:US2015/0073385A1
Pub. Dt.:Mar. 12, 2015
Inventors.: Bradley Lyon ,Adranius Aria ,Morteza Gharib
(CIT,CA,US)
 A medical device in the form of a transdermal drug delivery
patch , comprising a base including two reservoirs, first
reservoir in fluid communication and horizontally offset from
the second reservoir, Covered by a flexible membrane(CNT-
polyimide, PDMS, Silicone dvt.).The patch held approx. 114µL
of fluid with 84µL in first reservoir ,22µL in second reservoir
and 8µL in channel.First pressing the patch in one location to
insert microneedles into skin .second pressing actuates the
reservoir and drive fluid from patch through microneedles into
skin.
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34. Fig: Dual reservoir transdermal drug delivery microneedles patch (Lyon et al,
2015)
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35. MICRONEEDLE PATCH AND PRODUCTION METHOD THEREFOR
Pub No.:US2017/0189661A1
Pub Dt.: Jul. 6 ,2017
Inventor :Jae Yeong LEE , seoul (kR)
The present inventors have studied on techniques for improving
properties of the micro-needle patches and found a structural and
methodological feature that a production cost may be reduced by
forming a gel membrane for delivery of a drug to be transferred
into a thin film ,in which a drug or skin cosmetic treatment fluid is
evenly distributed on the gel membrane by an electrospinning or
electrospraying method, so that the drug or skin cosmetic
treatment fluid permeates smoothly into the skin, and by quickly
transferring the drug or skin cosmetic treatment fluid of the gel
membrane to the skin via passages, to thereby improve a healing
and skin cosmetic treatment effect of the skin, and completed the
present invention more economical, applicable, and competitive.
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36. DISSOLVABLE MICRONEEDLE ARRAYS FOR
TRANSDERMAL DELIVERY TO HUMAN SKIN
Patent No.: US 8,834,423 B2
Date of Patent: Sep. 16, 2014
Inventors: Louis D. Falo, Jr., Wexford,urak Ozdoganlar, Sewickley, PA (US)
3/5/2019 36
 A dissolvable microneedle array comprising: a base portion; and a
plurality of microneedles, wherein respective microneedles further
comprises a fillet portion, being located at the area where
respective microneedles contact the base portion. wherein each
microneedle comprises a plurality of layers of dissoluble
biocompatible material (carboxymethylcellulose). wherein the
bioactive component comprises at least two different bio active
components. This method involves using solid microneedle arrays
that are biodegradable and dissolvable. This method combines the
physical toughness of solid microneedles with relatively high
bioactive material capacity, while retaining desired attributes of
simple fabrication, storage and application.

37. MICRONEEDLE BASED TRANSDERMAL
DRUG DELIVERY DEVICE AND METHOD
Pub. No.: WO 2013/165715 Al
Pub.Dt.:7 November 2013
Inventors: MO, Jianwei, Fre mont,WANG, Guanjun; Saint Nicholas C , Fremont,
California (US).
 The device has a clamshell configuration, where the top part of
the clamshell holds chambers configured to store liquid drugs,
and also configured to store one or more spring operated
plungers, and at least one microneedle. The top portion of the
device is attached to the bottom portion of the device by a
combination hinge and a moveable shutter mechanism. In its shut
position, the shutter mechanism prevents the plungers from
moving, and the open shutter position releases the plunger. When
the user applies the bottom of the device to the user's skin and
presses on the top portion with enough force to overcome a
detent mechanism, the top portion pivots against the bottom
portion forcing the microneedle through an aperture and into the
skin painlessly. Pressing on the shutter mechanism then results in
drug self administration.
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38. 3/5/2019 38

39. EMBEDDABLE MICRO-NEEDLE PATCH FOR
TRANSIDERMAL DRUG DELVERY AND METHOD OF
MANUFACTURING THE SAME
Pub No .:US 2014/0005606 A1
Pub Dt .:Jan. 2, 2014
Inventors: Mei-Chin CHEN; Shih-Fang HUANG, Tainan City (TW)
 The present invention provides an embeddable micro-needle
patch for transdermal drug delivery comprising a Supporting
Substrate, on which its surface comprises a plurality of
protruded Supporting shafts; a biodegradable carrier formed by
a biodegradable polymeric material and disposed on the
Supporting shafts; and a drug encapsulated in the
biodegradable carrier. When the embeddable micro-needle
patch for transdermal drug delivery is applied on skin for a
predetermined time, the biodegradable carrier is embedded into
skin by separating from the Supporting shafts, and the
biodegradable carrier is Swollen and then degraded in skin to
release the drug encapsulated in the biodegradable carrier into
skin at a rate of 1% loaded drug per day to 99% loaded drug
per day.
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40. 3/5/2019 40

41. 3/5/2019 41

42. RESEARCH ARTICLES
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43. Carbon Nanotube-Polyimide Composite Microneedles for
Rapid Transdermal Drug Delivery
Bradley Lyon, Adrianus Indrat Aria, Morteza Gharib. Graduate Aeronautics Laboratories,
California Institute of Technology, Pasadena, CA
 Purpose: Carbon nanotubes (CNT) and other self-assembly
nanomaterials allow for direct access to the nano and micro length scales
for fabricating biomedical devices. Here, we demonstrate the use of CNT
patterned into 100 um hollow microbundles as a scaffolding for making
CNT-polyimide composite microneedles. Polyimide is wicked passively
through the CNT microneedle to create a composite material that is strong
enough to achieve skin penetration while retaining the shape of the CNT
microbundles. Successful in vitro skin penetration in porcine is
demonstrated. Potential drug delivery rates are characterized by
experiment and model. Controllable flow rates can be achieved over a
wide range from 0.01mL/s to 10mL/s.
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44.  Methods: Carbon nanotubes are fabricated on a silicon wafer coated with 1
nm iron catalyst that is patterned into hollow rings (100 um outer dia., 25
um inner dia.) thru photolithography and electron beam evaporation. During
chemical vapour deposition, ethylene and hydrogen gas interact with
sintered catalyst nanoparticles to form vertically-aligned CNT with
approximate diameter of 25nm. Polyimide is spin coated onto the CNT to
create a uniform composite of CNT and polymer while simultaneously
creating a flexible base for the array . For lightly viscous polyimide, such as
Poly(3,3′,4,4′benzophenonetetracarboxylic dianhydride-co-
4,4′oxydianiline/1,3-phenylenediamine), we demonstrate that curing can be
done thermally without clogging the central cavity. Poor mechanical
adhesion between polyimide and silicon allow the resulting device to be
easily removed from the silicon mechanically with tweezers. Fluid flow
through the device is achieved by removing the device from its silicon
substrate and transferring it onto a microfluidic port with an inner diameter
of 4mm allowing for actuation of approximately 6-7 needles. The port was
tested with two reservoirs: (1) a 20mL syringe to demonstrate steady flow
and a (2) PDMS skin patch to demonstrate release of small therapeutic
doses (~0.5mL). In vitro skin penetration experiments are performed by
placing the array into contact with constant force (1.5kg) into full thickness
dorsal skin from Yucatan Miniature Swine. Microneedles are coated in dry
methylene blue power prior to penetration which is reconstituted into a dye
upon contact with interstitial fluid from the skin.
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45.  Results: Fluid Delivery is achieved for steady flow release. Despite the
very small 25um cavity diameter per needle, the integrated area of the
microneedle array allows for very low hydraulic resistance as seen by the
roughly 1mL/s fluid release . A Poiseuille flow model was used to
characterize the achievable drug delivery . rates given different needle
sizes and number of total needles in the array. Flow rates as high as
10mL/s and as low as 0.01mL/s can be achieved (2). Generally, the same
flow rate achieved with a standard hypodermic can be achieved with 100
microneedles over an order of magnitude smaller than the hypodermic. In
Vitro Skin Penetration is seen for 100um dia. polyimide needles. Skin
penetration is optimally achieved without damaging the microneedle at a
needle height of about 200um.
3/5/2019 45

46.  Conclusions: The use of patterned CNT
microbundles is demonstrated as a scaffolding
for creating a CNT-polyimide composite
microneedle. Polyimide conformally coats the
CNT and creates a composite which is strong
enough to achieve skin penetration. In principle,
the fabrication technique is not polymer specific
and can be generalized to a wide range of
polymers. By using CNT scaffolding, we can
tune the needle size to as low as 100nm as well
as specify the number of needles and needle
spacing to achieve optimal transdermal drug
delivery.
3/5/2019 46

47. Coated microneedle arrays for transcutaneous delivery of
live virus vaccines
Anto Vrdoljaka, Marie G. McGratha, John B. Careya, Simon J. Draperb, Adrian V.S. Hillb, Conor
O’Mahonyc, Abina M. Creana, and Anne C. Moore
 Vaccines are sensitive biologics that require continuous refrigerated storage to
maintain their viability. The vast majority of vaccines are also administered using
needles and syringes. The need for cold chain storage and the significant logistics
surrounding needle-and-syringe vaccination is constraining the success of
immunization programs. Recombinant live viral vectors are a promising platform for
the development of vaccines against a number of infectious diseases, however
these viruses must retain infectivity to be effective. Microneedles offer an effective
and painless method for delivery of vaccines directly into skin that in the future could
provide solutions to current vaccination issues. Here we investigated methods of
coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA)
vectors onto solid microneedle arrays. An effective spray-coating method, using
conventional pharmaceutical processes, was developed, which produces arrays with
a unique coating of viable virus in a dry form around the shaft of each microneedle
on the array. Administration of live virus-coated microneedle arrays successfully
resulted in virus delivery, and induced response in mice that was comparable to that
obtained by needle-and-syringe intradermal immunization. To our knowledge, this is
the first report of successful vaccination with recombinant live viral vectored
vaccines coated on microneedle delivery devices.
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48. Dissolving Microneedle Patches for Dermal
Vaccination
M. Leone & J. Mönkäre & J. A. Bouwstra & G. Kersten
 The dermal route is an attractive route for vaccine
delivery due to the easy skin accessibility and a
dense network of immune cells in the skin. The
development of microneedles is crucial to take
advantage of the skin immunization and
simultaneously to overcome problems related to
vaccination by conventional needles (e.g. pain,
needle-stick injuries or needle re-use). This article
focuses on dissolving microneedles that after
penetration into the skin dissolve ,releasing the
encapsulated antigen.
3/5/2019 48

49. Sodium Alginate Microneedle Arrays Mediate the
Transdermal Delivery of Bovine Serum Albumin
Yusuf K. Demir*, Zafer Akan, Oya Kerimoglu
purpose: The ‘‘poke and release’’ strategy for the delivery of macromolecules using
polymeric microneedle (MN) is of great importance because it eliminates microneedle reuse, the
risks of biohazardous sharps and cross contamination, and it requires no special disposal
mechanism. The main objective of this study was the determination of the stability and delivery of
bovine serum albumin (BSA) that was transported across human skin via sodium alginate
(SA) microneedle arrays (MNs) and SA needle free patches using two different analytical
methods.
 M e t h o d : The capability of two analytical methods, the bicinchoninic acid (BCA) assay
and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), to precisely
detect and quantify BSA within different types of polymeric MNs was assessed. The ex vivo
protein release of BSA across dermatomed human abdominal skin from 10 w/w SA MNs was
compared to that from needle-free patches using Franz diffusion cells. The developed
applicator was mechanically characterized using a Texture Analyzer. The patch mould and its
components were fabricated using a rapid prototyping machine.
 Conclusion: The BCA method was able to precisely detect BSA that had been loaded into
SA MNs. However, the use of SDS-PAGE as the analytical method resulted in significantly
different amounts of BSA recovered from differently conditioned polymeric MNs. The
permeation of BSA across dermatomed human abdominal skin by SA MNs, which were
composed of 100 pyramidal needles, increased by approximately 15.4 fold compared to
the permeation obtained with SA needle-free patches. The ease of use of the applicator
during the release studies was also demonstrated, as was its mechanical characterization.
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50. Microneedle-Assisted Permeation of Lidocaine
Carboxymethylcellulose with Gelatine Co-polymer
Hydrogel
Atul Nayak & Diganta B. Das & Goran T. Vladisavljevi
 Purpose Lidocaine hydrochloride (LidH) was formulated in sodium carboxymethyl
cellulose/ gelatin (NaCMC/GEL) hydrogel and a ‘poke and patch’ microneedle
delivery method was used to enhance permeation flux of LidH.
 Methods The microparticles were formed by electrostatic interactions between
NaCMC and GEL macromolecules within a water/oil emulsion in paraffin oil and the
covalent crosslinking was by glutaraldehyde. The GEL to NaCMC mass ratio was
varied between 1.6 and 2.7. The LidH encapsulation yield was 1.2 to 7% w/w. LidH
NaCMC/GEL was assessed for encapsulation efficiency, zeta potential, mean
particle size and morphology. Subsequent in vitro skin permeation studies were
performed via passive diffusion and microneedle assisted permeation of LidH
NaCMC/GEL to determine the maximum permeation rate through full thickness skin
 Result:LidH 2.4% w/w LidH NaCMC/GEL 1:2.3 crossed the minimum
therapeutic drug threshold with microneedle skin permeation in less than 70
min.
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51. Rapidly Dissolvable Microneedle Patches for
Transdermal Delivery of Exenatide
Zhuangzhi Zhu & Huafei Luo & Wangding Lu & Hansen Luan & Yubo Wu & Jing Luo &
Youjie Wang & Jiaxin Pi & Chee Yen Lim & Hao Wang
 Purpose To assess the feasibility of transdermal delivery of exenatide (EXT)
using low-molecular-weight sodium hyaluronate (HA) dissolving microneedles
(MNs) patches for type 2 diabetes mellitus therapy.
 Methods Micromold casting method was used to fabricate EXT loaded
dissolving MNs. The characteristics of prepared MNs including mechanical
strength, in vitro/in vivo insertion capacity, dissolution profile and storage
stability were then investigated. Finally ,the in vivo pharmacokinetics and
hypoglycemic effects were compared with traditional subcutaneous (SC)
injection.
 Results EXT-loaded dissolving MNs made of HA possessed sufficient
mechanical strength and the strength could be weakened as the water
content increases.The EXT preserve pharmacological activity during
fabrication and one-month storage. With the aid of spring-operated applicator,
dissolving MNs could be readily penetrated into the skin in vitro/in vivo, and
then rapidly dissolved to release encapsulated drug within 2 min. Additionally,
transepidermal water loss (TEWL) determinations showed that skin’s barrier
properties disrupted by MNs recovered within 10– 12h.Transdermal
pharmacokinetics and antidiabetic effects studies demonstrated that fabricated
EXT MNs induced comparable efficacy to SC injection.
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52. A Patchless dissolving Mns delivery system
enabling rapid and efficient tdds
Inventors: hayan F. Lahiji, Manita Dangol & Hyungil Jung
Department of Biotechnology, Yonsei University, Yonseiro
 Fabrication: Fabrication of dissolving microneedles
(DMNs). Humalog insulin loaded carboxymethyl
cellulose (CMC) polymer was prepared by mixing 10%
CMC powder with distilled water and then diluting insulin
(0.2 IU) in phosphate-buffered saline (PBS, pH 7.4) at
37 C. The insulinCMC solution was dispensed over the
holes; holes were arranged in 3 3 3 arrays on an
automated X, Y and Z stage (SHOT mini 100-s,
Musashi). The solution was dispensed at a rate of 0.6
kg.f/cm and 0.05 s/aliquot. A custom-made, rate-
controllable stage capable of upward and downward
motion was designed in order to accurately push and
pull the two smooth solid plates, which were parallel and
faced each other.
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53. 3/5/2019 53

54. Any Questions
??????
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55. References
 Reed ML, Lye WK (2004) Microsystems for drug and gene delivery.
Proc IEEE 92(1):56–75. doi:10.1109/JPROC.2003.820542
 Sammoura F, Kang J, Heo YM, Jung TS, Lin L (2007) Polymeric
microneedle fabrication using a microinjection molding technique.
Microsyst Technol 13:517–522. doi:10.1007/s00542-006- 0204-1
 Oh KW, Ahn CH (2006) A review of microvalves. J Micromech
Microeng 16(5):R13–R39. doi:10.1088/0960-1317/16/5/R01
 Langer R (1998) Drug delivery and targeting. Nature 392(6679)
(Suppl):5–10
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56. References
 Cheung, K., Han, T. & Das, D. B. Effect of Force of Microneedle Insertion
on the Permeability of Insulin in Skin. Journal of diabetes science and
technology 8, 444–452 (2014).
 . Trim, J. C. & Elliott, T. S. A review of sharps injuries and preventative
strategies. J Hosp Infect 53, 237–42 (2003).
 Nir, Y. et al. Fear of injections in young adults: prevalence and
associations. Am J Trop Med Hyg 68, 341–4 (2003).
 Simonsen, L. et al. Unsafe injections in the developing world and
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