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Transdermal delivery of biologics using microneedles and other technologies Mark Prausnitz Georgia Institute of Technology Atlanta, GA

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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

Prausnitz & Langer, Nature Biotechnology (2008)

Transdermal drugs approved by the US FDA

Histological structure of human skin

stratum corneum viable epidermis

dermis

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

stratum corneum viable epidermis

dermis

1st generation transdermal delivery

stratum corneum viable epidermis

dermis

1st generation transdermal delivery

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) microneedles

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

Microneedle research is increasing

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

Dissolving polymer microneedles

Dissolving polymer microneedles

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.

Products under development

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