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TRANSCRIPT
Transdermal delivery of biologics using
microneedles and other technologies
Mark Prausnitz
Georgia Institute of Technology
Atlanta, GA
Three generations of transdermal delivery - no enhancement needed
- increase stratum corneum permeability
- increase permeability targeted to stratum corneum
Delivery of biologics using microneedle
patches - human studies of microneedle patches
- influenza vaccination
Outline of Talk
Three generations of transdermal delivery
1st generation
· conventional patches
2nd generation
· chemical enhancers
· non-cavitational ultrasound
· iontophoresis
3rd generation (nano and micro)
· cavitational ultrasound
· electroporation
· chemical enhancer mixtures
· microneedles
· thermal ablation
· microdermabrasion
Three generations of transdermal delivery
No enhancement needed 1st generation
· conventional patches
2nd generation
· chemical enhancers
· non-cavitational ultrasound
· iontophoresis
3rd generation (nano and micro)
· cavitational ultrasound
· electroporation
· chemical enhancer mixtures
· microneedles
· thermal ablation
· microdermabrasion
Three generations of transdermal delivery No enhancement needed
Limited to drugs with
appropriate properties
Increase stratum corneum
permeability
1st generation
· conventional patches
2nd generation
· chemical enhancers
· non-cavitational ultrasound
· iontophoresis
3rd generation (nano and micro)
· electroporation
· cavitational ultrasound
· chemical enhancer mixtures
· microneedles
· thermal ablation
· microdermabrasion
stratum corneum viable epidermis
dermis
chemical enhancer
2nd generation transdermal delivery chemical enhancer
stratum corneum viable epidermis
dermis
2nd generation transdermal delivery noncavitational ultrasound
ultrasound probe
sound waves
stratum corneum viable epidermis
dermis
2nd generation transdermal delivery iontophoresis
electrode electrode
current
Three generations of transdermal delivery No enhancement needed
Limited to drugs with
appropriate properties
Increase stratum corneum
permeability
Insufficient targeting of
stratum corneum
Increased permeability
targeted to stratum corneum
1st generation
· conventional patches
2nd generation
· chemical enhancers
· non-cavitational ultrasound
· iontophoresis
3rd generation (nano and micro)
· cavitational ultrasound
· electroporation
· chemical enhancer mixtures
· microneedles
· thermal ablation
· microdermabrasion
3rd generation transdermal delivery (nano) cavitational ultrasound
stratum corneum viable epidermis
dermis
sound waves
ultrasound probe
Cavitational
bubble
activity at
skin surface
stratum corneum viable epidermis
dermis
3rd generation transdermal delivery (nano) electroporation
stratum corneum
viable epidermis and dermis
voltage
electrode electrode
stratum corneum viable epidermis
dermis
chemical enhancer mixture
3rd generation transdermal delivery (nano) chemical enhancer mixtures
Mixture
composition
dilutes and
changes
stratum corneum viable epidermis
dermis
3rd generation transdermal delivery (micro) microneedles
microneedle patch
stratum corneum viable epidermis
dermis
3rd generation transdermal delivery (micro) thermal ablation
thermal ablation device
stratum corneum viable epidermis
dermis
3rd generation transdermal delivery (micro) thermal ablation
stratum corneum viable epidermis
dermis
3rd generation transdermal delivery (micro) microdermabrasion
microdermabrasion handpiece
stratum corneum viable epidermis
dermis
3rd generation transdermal delivery (micro) microdermabrasion
Three generations of transdermal delivery No enhancement needed
Limited to drugs with
appropriate properties
Increase stratum corneum
permeability
Insufficient targeting of
stratum corneum
Increase permeability
targeted to stratum corneum
Requires devices and/or
tissue removal
1st generation
· conventional patches
2nd generation
· chemical enhancers
· non-cavitational ultrasound
· iontophoresis
3rd generation (nano and micro)
· cavitational ultrasound
· electroporation
· chemical enhancer mixtures
· microneedles
· thermal ablation
· microdermabrasion
Three generations of transdermal delivery
many successful products
(no biologics)
in some patches
physical therapy (NSAIDs)
lidocaine, fentanyl, sweat test
(no biologics)
lidocaine
research
research
influenza vaccine, clinical trials
clinical trials
research
1st generation
· conventional patches
2nd generation
· chemical enhancers
· non-cavitational ultrasound
· iontophoresis
3rd generation (nano and micro)
· cavitational ultrasound
· electroporation
· chemical enhancer mixtures
· microneedles
· thermal ablation
· microdermabrasion
Three generations of transdermal delivery - no enhancement needed
- increase stratum corneum permeability
- increase permeability targeted to stratum corneum
Delivery of biologics using microneedle
patches - human studies of microneedle patches
- influenza vaccination
Outline of Talk
Microneedles deliver drugs to the skin
using a simple patch
Stratum corneum Viable epidermis (Langerhans cells)
Dermis (dermal dendritic cells)
microneedle patch
Drug delivery mechanisms
using microneedles
Solid
MN
Coated
MN
Dissolving
MN
Hollow
MN
stratum corneum
viable epidermis
dermis
Microneedles deliver drugs to the skin
using a simple patch
650
um
Green dye represents
location of drug
Manufacturing Low-cost fabrication Transportation and storage Small package size Possible thermal stability Patient administration No reconstitution Possible reduced dose Minimally trained personnel Waste disposal Difficult or impossible reuse Reduced or no disposal volume
Microneedles meet public health needs
Tolerability of
placebo microneedle patch
Determine the tolerability of
a placebo microneedle patch
in human subjects.
Acceptability of influenza vaccination
using a microneedle patch
Determine the acceptability
of a placebo microneedle patch
in future use for influenza vaccination
in untrained human subjects.
Acceptability of influenza vaccination
using a microneedle patch
Normally
vaccinated
Normally
unvaccinated
46%
54%
Acceptability of influenza vaccination
using a microneedle patch
Normally
vaccinated
Normally
unvaccinated 54% 54%
Acceptability of influenza vaccination
using a microneedle patch
Normally
vaccinated
Normally
unvaccinated
Influenza vaccination
using a microneedle patch
A phase I study of the safety,
reactogenicity, acceptability
and immunogenicity of
inactivated influenza vaccine
delivered by microneedle patch
or by hypodermic needle.
Three generations of transdermal delivery - no enhancement needed
- increase stratum corneum permeability
- increase permeability targeted to stratum corneum
Delivery of biologics using microneedle
patches - human studies of microneedle patches
- influenza vaccination
Summary of Talk
Mark Prausnitz serves as a consultant and is an inventor on patents licensed to companies developing products related to this presentation. This potential conflict of interest is managed by Georgia Tech and Emory University
Conflict of interest disclosure
Current lab members
Jaya Arya, Donna Bondy, Bryce Chiang, Brandon Gerberich, Yasmine Gomaa, Sebastien Henry,
Stefany Holguin, Jessica Joyce, Jae Hwan Jung, Priya Kalluri, Chandana Kolluru, Jeong Woo Lee,
Devin McAllister, Joshua Palacios, Wilmarie Medina-Ramos, Matthew Mistilis, Monica Perez,
Winston Pewin, Sanjay Rawat, Andrew Romanyuk, Pradnya Samant, Andrew Tadros.
Past lab members
Samantha Andrews, Harold Azencott, Paul Canatella, Prerona Chakravarty,, Hyo-Jick Choi,
Seong-O Choi, Young-Bin Choy, Leonard Chu, Stephen Cochran, Arlena Coulberson, Tanicia Daley,
Shawn Davis, Christina Easley, Chris Edens, Esi Ghartey-Tagoe, Harvinder Gill, Michael Gray,
Xin Dong Guo, Jyoti Gupta, Hector Guzman, Daniel Hallow, Yasuhiro Hiraishi, Josh Hutcheson,
Jason Jiang, Shilpa Kaushik, Yeu-Chun Kim, Yoo Chun Kim, Jin Liu, Ying Liu, Saffar Mansoor,
Wijaya Martanto, James Norman, Han Jung Park, Jung-Hwan Park, Seonhee Park, Samir Patel,
Mychael Scoggins, Aritra Sengupta, Sean Sullivan, Cetin Tas, Ping Wang, Hong-Wei Yang,
Vladimir Zarnitsyn.
Collaborators
Mark Allen, Andreas Bommarius, Richard Compans, Henry Edelhauser, Ross Ethier, Eric Felner,
Courtney Jarrahian, Baoming Jiang, Sang-Moo Kang, Uday Kompella, Mikolaj Milewski,
Mark Mulligan, Steve Oberste, Paul Rota, Suraj Sable, Ioanna Skountzou, Naresh Thadhani,
William Weldon, Chinglai Yang, Darin Zehrung
Funding sources
CDC, Gates Foundation, Georgia Research Alliance, NIH, NSF, WHO .
Acknowledgements