ABOUT DISSOLVING MICRONEEDLES, WHY, PRELUDE MICRONEEDLE MATERIAL FABRICATION PROCESS CHARACTERIZATION APPLICATION FUTURE PATHWAYS

1. DISSOLVING MICRONEEDLES
(DMN)
AN OUTLOOK
C.SWORNA KUMARI
C.SWORNA KUMARI

2. ROAD MAP…
• PRELUDE
• MICRONEEDLE MATERIAL
• FABRICATION PROCESS
• CHARACTERIZATION
• APPLICATION
• FUTURE PATHWAYS
C.SWORNA KUMARI

3. PRELUDE
WHY DMN …?
C.SWORNA KUMARI
• Less painful way of delivering drugs for transdermal delivery
• Biologically non toxic and Produced with high precision,
accuracy and low cost
• Environmentally friendly solution
• Leaving no dangerous or wasteful products behind
• Cold-chain supply costs are reduced
• Easy and safe to use
• Less adverse effects
Shubhmita Bhatnagar,Pradeeptha Reddy Gadeela, Pranathi Thathireddy & Venkata Vamsi Krishna Venuganti Microneedle-based dru
delivery: materials of construction, Journal of Chemical Sciences volume 131, Article number: 90 (2019)

4. Ultra small needles (length 10-1000µm and width 10-
50µm)
Made up of water soluble materials
Which creates pore in the skin and release the drug
C.SWORNA KUMARI

5. DISSOLVING MICRO NEEDLE MATERIAL
Disolving
Micro Needle
material
Dissolving
material
BioPolymer
material
Solid material
C.SWORNA KUMARI

6. DISSOLVING MICRO NEEDLE MATERIAL
Dissolving material
Chondroitin sulfate,
galactose,
Poly
methylvinylethercomaleic
acid (PMVE/MA),
Polyvinylpyrrolidone(pvp),
Dextran,
Dextrin,
Maltose,
Fibroin,
Carboxy methyl cellulose
Biopolymer material
Polyglycolic acid,
Polylactic acid,
Polylacticco glycolic acid.
Solid material
Polymethyl meth-acrylate
(pmma),
SU-8,
Maltose,
Silicon.
C.SWORNA KUMARI

7. FABRICATION PROCESS OF DMN
C.SWORNA KUMARIReference:Aoife M. Rodgers, Aaron J. Courtenay & Ryan F. Donnelly, Dissolving microneedles for intradermal vaccination: manufacture,
formulation, and stakeholder considerations, Expert opinion on drug delivery 2018, VOL. 15, NO. 11, 1039–104

8. FABRICATION PROCESS- MOLDING AND CASTING
C.SWORNA KUMARI
Reference:Jeong W. Lee a , Jung-Hwan Park b , Mark R. Prausnitz , Dissolving microneedles
for transdermal drug delivery,j.biomaterials.2007.12.048

9. FABRICATION OF MICRO-PILLAR INTEGRATED
DISSOLVING MICRONEEDLES (P-DMNS)
C.SWORNA KUMARI
Reference: Seunghee Lee , Shayan Fakhraei Lahiji , Jeesu Jang , Mingyu Jang and Hyungil Jung,Micro-Pillar Integrated Dissolving
Microneedles for Enhanced Transdermal Drug Delivery, Pharmaceutics 2019, 11, 402; doi:10.3390/pharmaceutics11080402

10. DAB = DROPLET-BORN AIR BLOWING
C.SWORNA KUMARI
Reference: Kim, J. D., Kim, M., Yang, H., Lee, K., & Jung, H. (2013). Droplet-born air blowing: Novel dissolving microneedle
fabrication. Journal of Controlled Release, 170(3), 430–436. doi:10.1016/j.jconrel.2013.05.026

11. UV LITHOGRAPHY
C.SWORNA KUMARI
Reference:Chong In Shin , Seong Dong Jeong , N Sanoj Rejinold & Yeu-Chun Kim,
Microneedles for vaccine delivery: challenges and future perspectives, Ther. Deliv. (2017) 8(6),
447–460
Lithography is a technique in which a light
source such as UV irradiated onto a masked
resist to produce a patterned resist, and by
controlling the light source and the position of
substrate, diverse shapes of microneedles can
be manufactured

12. INCLINED DEEP X-RAY LITHOGRAPHY
C.SWORNA KUMARI
Reference:Chong In Shin , Seong Dong Jeong , N Sanoj Rejinold & Yeu-Chun Kim,
Microneedles for vaccine delivery: challenges and future perspectives, Ther. Deliv. (2017) 8(6),
447–460

13. DRAWING LITHOGRAPHY
C.SWORNA KUMARI
Reference: Jeong Woo Lee , Mee-Ree Han , and Jung-Hwan Park Polymer microneedles for transdermal drug delivery, Journal of
Drug Targeting, 2013; 21(3): 211–223

14. Characteristic Characterization method
Appearance Microscopy techniques
Antigen distribution in MNs Confocal microscopy
Water content Thermogravimetric analyser
Karl Fischer
Moisture balance
Antigen stability Immunogenicity
Antigenicity: ELISA, SRID, virus titration Physico-chemical
characterization: intrinsic fluorescence, CD, SDS-PAGE Aggregation:
HP-SEC, NTA, MFI, AF4, TEM, DLS
Mechanical strength Displacement-force test station
Skin piercing efficiency Skin staining and histological sections
Dissolution of MNs Dissolution of MNs in vitro
Change in MN tip length after skin insertion
Antigen localization into the skin Microscope analysis of skin sections or confocal microscopy analysis of
intact skin Analysis of histological skin sections
Antigen quantification Quantification of antigen concentration after in vitro dissolution of
dMNs by suitable methods (e.g. UV-vis, fluorescence or ELISA)
Quantification of antigen delivered into the skin by e.g. radioactivity or
infrared imaging
Stability after storage Forced (elevated humidity and temperature) and real time
stability testing
C.SWORNA KUMARI
CHARACTERIZATION OF DISSOLVING MICRONEEDLES

15. Reference: M. Leo,ne & J. Monkare & J. A. Bouwstra & G. Kersten Dissolving Microneedle Patches for Dermal Vaccination, Pharm Res
DOI 10.1007/s11095-017-2223-2
Challenges
of dMN
Preparation
Antigen
Wastage
Antigen and
Adjuvant
Loading
Fabrication
Aimed to
Improve
Delivery
Efficiency
Antigen
Degradation
Sterility
C.SWORNA KUMARI

16. APPLICATIONS
C.SWORNA KUMARI
Reference: , Ying Hao , Wei Li, XingLi Zhou, Fan Yang, and ZhiYong Qian., Microneedles-Based Transdermal Drug Delivery Systems: A
ReviewJournal of Biomedical Nanotechnology Vol. 13, 1581–1597, 2017
Delivery to the
skin
• Approximately 20 drugs with approval from the Food and Drug
Administration (FDA) as transdermal patches all have molecular weights
below 400 Da, relatively lipophilic and require low doses
Biotherapeutic
• Biotherapeutic drugs, such as peptides, proteins, DNA and RNA, are large
molecules that cannot easily be administered transdermally
Influenza
vaccine
• Influenza vaccination with coated microneedles has been extensively
studied in recent years, showing complete protection against lethal viral
infection after vaccination using H1N1 and H3N2 seasonal strains in mice

17. RABIES VACCINATION IN DOGS USING A DISSOLVING
MICRONEEDLE PATCH
C.SWORNA KUMARI
Reference:Jaya M. Arya , Kristopher Dewitt , Maya Scott-Garrard , Yu-Wei Chiang, Mark R. Prausnitz 2017. Rabies vaccination in dogs
using a dissolving microneedle patch. / Journal of Controlled Release 239 (2016) 19–26
.
(A)Microneedle
(PVA)patch
containing
sulforhodamine dye
applied to skin.
(B) Same section of
skin imaged after
microneedle patch
application and
removal, which
shows a grid
where microneedles
punctured the skin
and delivered the
dye. Microneedle
patches (C)
before and (D) after
insertion into skin.

18. AVIAN INFLUENZA DNA VACCINE USING DMN
C.SWORNA KUMARI
Kim, Y.C., Song, J.M., Lipatov, A.S., Choi, S.O., Lee, J.W., Donis, R.O., Compans, R.W., Kang, S.M.
and Prausnitz, M.R., 2012. Increased immunogenicity of avian influenza DNA vaccine delivered to
the skin using a microneedle patch. European journal of pharmaceutics and biopharmaceutics, 81(2),
pp.239-247.
Microneedles coated with Cy3-
stained HA DNA vaccine.
(A) Representative bright-field
(i) and fluorescence (ii)
micrographs of microneedles
coated with HA DNA vaccine
(scale bar=1 mm).
(B) Representative bright-field
(i) and fluorescence (ii–vi)
micrographs of a microneedle
coated with HA DNA vaccine
(i, ii) before insertion and (iii)
30 s (iv) 60 s (v)
120 s and (vi)180 s after
insertion into mouse skin in
vitro (scale bar = 200 μm).

19. MICRONEEDLES USED FOR TIMELY METABOLIC
ANALYSIS
C.SWORNA KUMARI
Reference: , Ying Hao , Wei Li, XingLi Zhou, Fan Yang, and ZhiYong Qian., Microneedles-Based Transdermal Drug Delivery Systems:
ReviewJournal of Biomedical Nanotechnology Vol. 13, 1581–1597, 2017

20. MICRONEEDLES USED FOR OBESITY THERAPY
C.SWORNA KUMARI
Reference: , Ying Hao , Wei Li, XingLi Zhou, Fan Yang, and ZhiYong Qian., Microneedles-Based Transdermal Drug Delivery Systems: A
ReviewJournal of Biomedical Nanotechnology Vol. 13, 1581–1597, 2017
Brown adipose tissue (BAT) could
help obesity to lose weight
White adipose tissue (WAT)-
storing exceeded energy.
Therefore, the transformation of
WAT into BAT is an attractive way
for the treatment of obesity.
In this work, a rosiglita-zone,
glucose oxidase (GOx), and
catalase (CAT)-loaded
nanoparticle-based degradable
microneedle (MN) patch
was developed to enable local
browning of WAT.
In vivo study further implied that
the microneedle patch could
lose the body weight of the mice
via the transformation of WAT into
BAT.

21. MICRONEEDLES USED FOR CANCER THERAPY
C.SWORNA KUMARI
(.
Schematic of the microneedle patch-assisted
delivery of anti-PD-1 (aPD1) for the skin
cancer treatment.
a) Schematic of the aPD1 delivered
by a microneedle patch loaded with
physiologically self-dissociated
NPs.
With GOx/CAT enzymatic system
immobilised inside the NPs by
double-emulsion method, the
enzyme-mediated conversion of
blood glucose to gluconic acid
promotes the sustained dissociation
of NPs, subsequently leading to the
release of aPD1
(b) The blockade of PD-1 by aPD1 to
activate the immune system to
destroy skin cancer cells. GOx:
glucose oxidase; CAT: catalase.

22. MICRONEEDLES USED FOR ANTI-INFLAMMATORY AND
ANALGESIC
C.SWORNA KUMARI
Reference: , Ying Hao , Wei Li, XingLi Zhou, Fan Yang, and ZhiYong Qian., Microneedles-Based Transdermal Drug Delivery Systems: A ReviewJournal of
Biomedical Nanotechnology Vol. 13, 1581–1597, 2017
Dissolvable MNs with anti-
CGRP patch to deliver
lidocaine, an analgesic
suitable for both acute and
chronic pain.
The designed
microneedle patch with high
drug loading could deliver
lidocaine into the skin and
release the active ingredient to
relieve acute and chronic pain

23. C.SWORNA KUMARI
DMN- DISEASE TARGETTED

24. Product name Company name Description of the product Use
Dermaroller® Dermaroller® Germany, White
Lotus
A cylindrical roller with solid
or metal microneedles, 0.2–2.5
mm in length.
Improve skin texture, treat
scars and hyperpigmentation.
C-8 (Cosmetic type) The Dermaroller Series by
Anastassakis K.
A needle length of only 0.13
mm (130 μm)
Used to enhance penetration of
topical agents.
CIT-8 (Collagen Induction
Therapy
The Dermaroller Series by
Anastassakis K.
A needle length of 0.5 mm (500
μm)
Used in collagen induction and
skin remodeling
MF-8 type The Dermaroller Series by
Anastassakis K.
A needle length of 1.5 mm
(1500 μm)
Treat scars.
MS-4 The Dermaroller Series by
Anastassakis K.
A Small cylinder, 1 cm length,
2 cm diameter, and 4 circular
arrays of needles which are 1.5
mm in length
Used on facial acne scars
MicroHyala® CosMed transdermal drug
delivery
Dissolving microneedle patch
with hyaluronic acid
Wrinkle treatment
LiteClear® Nanomed skincare Solid silicon microneedles are
used as pre-treatment and then
drug applied topically.
Treats acne and skin blemishes
Soluvia® Sanofi Pasteur Europe Hollow microneedle attached
to a syringe
Influenza vaccination
h-patch Valeritas Small adhesive machine like
patch is used
To deliver drugs in
subcutaneous tissue (insulin)
Microstructured transdermal
system
3M Hollow microneedle To deliver biologics and other
small molecules
C.SWORNA KUMARI

25. FUTURE PATHS…
A 3D-PRINTED MICRONEEDLE FOR ANTICANCER THERAPY
OF SKIN TUMOURS
• 3D printed polymeric microneedle arrays were fabricated for enhanced
cisplatin delivery to A-431 epidermoid skin tumours for cancer treatment
• Using stereolithography (SLA) biocompatible photopolymer resin followed
by coating of cisplatin formulations using inkjet dispensing on the needle
surface
C.SWORNA KUMARIReference: Md jasimuddin,nicolaosscoutar,sophia ,economidou, clementinegiraud, babur, Z.Chowdhryryan,f.Donnellydennisdouroumi,
3d printed microneedles for anticancer therapy of skin tumours, Volume 107, February 2020.
Abdominal porcine skin
In vitro fluorescent images

26. 4D-PRINTED MICRONEEDLES FOR DRUG DELIVERY
AND BIOSENSING
C.SWORNA KUMARI
•This microneedle array has backward-
facing barbs that interlock with tissue when
inserted, enhancing adhesion
•4D-printed microneedle array will allow
for more robust and sustained use of
minimally invasive, pain-free and easy-to-
use microneedles for delivering drugs,
healing wounds, biosensing and other soft
tissue applications
•This platform could be further developed
for more stable and robust drug delivery,
collection of bio-fluids and biosensing in
future

27. THANK YOU
C.SWORNA KUMARI