MICRONEEDLES FORMICRONEEDLES FOR INTRADERMAL VACCINE
DELIVERYDELIVERY
Richard W. COMPANSEmory University School of MedicineEmory University School of Medicine
Influenza Pathogenesis and Immunology Research Center Director
Concept of coated microneedlesConcept of coated microneedles
MicroneedleStratum corneum (10 m) TRANSPORT BARRIER
Drug/vaccine coatingViable
Epidermis p(50-100 m)
Dermis (1-2 mm)
50 m
Concept of coated microneedlesConcept of coated microneedles
MicroneedleStratum corneum (10 m) TRANSPORT BARRIER
Drug/vaccine coatingViable
Epidermis p(50-100 m)
Dermis (1-2 mm)
50 m
Microneedle fabricationMicroneedle fabrication
Material : Stainless steel sheetsMaterial : Stainless steel sheetsCutting tool : Infrared laserD b i El t li hiDe-burring : Electropolishing
(A) SILICON MICRONEEDLES FABRICATED BY REACTIVE ION ETCHING AND (B) METAL MICRONEEDLES FABRICATED BY LASER
ETCHINGETCHING
_____________________________________A B
POTENTIAL ADVANTAGES OFPOTENTIAL ADVANTAGES OF MICRONEEDLE PATCH VACCINES
• Painless• Safe disposalp• Lower vaccine dose• Improved vaccine efficacy p y• Increased stability?• Low costLow cost• Rapid distribution• Possible self-administrationPossible self administration
Dip coatingA B C
Substrate
Coating solution
Capillary rise at micro-length scales C p y se c o e g sc esgB
Cosh
)(
Capillary rise between plates =
h
g = liquid/air interfacial tension = liquid density = contact angle
eg.: Water
B = needle spacing = 1 mm
gB = plate spacing
B = needle spacing = 1 mm
Capillary rise = h = 5 mm
A Incomplete B Contaminated b t t
Microneedl
coating substrate
e
Contaminated substrate
Sub.
Microneedle coatingMicroneedle coating• Coating solution additives:Coating solution additives:
– SURFACTANT – Poloxamer (F-68)• VISCOSITY ENHANCER - Sodium
carboxymethyl cellulose (CMC)
500 mm
Effect of concentration and number of i dlmicroneedles
D i N b f i dl
0.1% 1% 2% 3% 4%0.01%
Drug concentration Number of microneedles
505
2 63
5
gs
1.8
2.6
1 5
2
2.5
3
in B
in c
oatin
gscr
onee
dle) 200 mm
1.92.13
4
min
B in
coa
ting
cron
eedl
e)
200 mm
0.002
0.5
1.0
0.0390
0.5
1
1.5
Mas
s of
vita
mi
( g
/ mic
0
1
2
Mas
s of
vita
m(
g / m
i
00.01% 0.10% 1% 2% 3% 4%
Concentration of vitamin B in coating solution (w/v%)
05 50
Number of microneedles in array
ARRAY OF 50 MICRONEEDLESARRAY OF 50 MICRONEEDLES COATED WITH RIBOFLAVIN
In vitro insertion and releaseIn vitro insertion and release
Rapid release Delivery of small p
Sc
molecule - calcein
200 mm
200 mm
50 needle array50-needle array
1 mm
Efficiency of deliveryEfficiency of delivery after insertion into the skin
Amount deposited inside the skin: 91%
Amount left on the skin surface: 2%Amount left on the skin surface: 2%
Amount left on the microneedle: 7%
MICRONEEDLES COATED WITH PROTEINMICRONEEDLES COATED WITH PROTEIN, DNA, AND MICROSPHERES
SSO G ORAPIDLY DISSOLVING POLYMER MICRONEEDLES
• Improved safety
• Polymerization at low temperaturey p
• Preservation of antigen• Preservation of antigen
• Effective penetration and dissolution
INSERTION CAPABILITIES AND MECHANICAL PROPERTIES OF POLYMER MICRONEEDLES
ARRAY CONTAINING 100 BIODEGRADABLE PLGA POLYMERBIODEGRADABLE PLGA POLYMER
MICRONEEDLES
RAPIDLY DISSOLVING CMCRAPIDLY DISSOLVING CMC MICRONEEDLES BEFORE AND AFTER
INSERTION INTO HUMAN CADAVER SKININSERTION INTO HUMAN CADAVER SKIN
MICRONEEDLES ARE 750 µm TALLµ
SITE OF MICRONEEDLESITE OF MICRONEEDLE PENETRATION AND DEPOSITION IN
HUMAN CADAVER SKINHUMAN CADAVER SKIN
SUMMARY/CONCLUSIONSSUMMARY/CONCLUSIONS
S lid t l i dl b ff ti l t d ith• Solid metal microneedles can be effectively coated with alternative vaccine formulations
• Intradermal delivery of vaccines occurs with high efficiencyefficiency
• Microneedle immunization results in strong humoral as• Microneedle immunization results in strong humoral as well as cellular immune responses
• Antigen containing microneedles can also be constructed using resorbable polymersg p y
SOME CURRENT DIRECTIONSSOME CURRENT DIRECTIONS
• Determine the protective efficacy of immunizationDetermine the protective efficacy of immunization
F l d d i i fl i• Focus on seasonal and pandemic influenza viruses
• Determine the breath of immunity induced by microneedle vaccine deliveryy
• Adjuvants to enhance immune responses to• Adjuvants to enhance immune responses to microneedle delivery
ACKNOWLEDGEMENTSACKNOWLEDGEMENTS
Emory University Georgia Institute of Technologyy y g gyIoanna Skountzou Mark PrausnitzDimitrios Koutsonanos Harvinder Singh GillChinglai Yang Sean SullivanChinglai Yang Sean SullivanLing Ye Vladimir ZarnitsynSang-Moo KangFu-Shi Quan Karolinska InstituteJaemin Song Jonas Sõderholm
Matti SãllbergMatti Sãllberg
NIAIDNIBIB