Getting under the skin

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    DECEMBER 2006 | VOLUME 9 | NUMBER 1272

    The needle and syringe may be on their way out as materials scientists begin to find better ways of delivering drugs through the skin.

    Mark Kendall | The University of Queensland, Australia |

    The mapping of the human genome1 in 2001

    has provided us with a means of deciphering the

    complex functions and interactions of our genes,

    chemicals, proteins, and cells. This understanding

    is being applied to develop advanced sensors

    and drugs for monitoring and treating major

    diseases. Consequently, an explosion of new drugs

    is expected in the next ten years. How will they

    be delivered effectively to the body? The most

    obvious and convenient drug delivery routes are

    via ingestion or inhalation. However, these are

    frequently inappropriate because drugs must survive

    the harsh environments of the gastrointestinal

    tract, lung lining, and the first-pass metabolism of

    the liver. As a result, the most common delivery

    route is the needle and syringe, a method invented

    in 1853.

    Despite being around for more than 150 years, the

    needle and syringe is far from perfect. Lets start

    with needle-phobia. Most of us do not like needles

    and, with many, needle-phobia can be a major

    impediment to the provision of important vaccines

    and drugs. But of greater concern is the risk of

    cross-contamination through needle-stick injuries in

    health workers. It is estimated by the World Health

    Organization (WHO) that one billion vaccination

    injections are administered through national

    immunization programs each year, and up to 30%

    of these injections are thought to be unsafe2. The

    primary risks are infection with hepatitis B and C and

    HIV. Consequently, effective needle-free vaccination

    strategies are a major priority of international groups

    and organizations, such as the WHO and the Global

    Alliance for Vaccines and Immunization (GAVI).

    However, the biggest limitation of the needle and

    syringe is that the delivery route simply does not

    work in the prevention, treatment, and monitoring

    of a range of currently untreatable diseases. This is

    because the needle and syringe is literally too blunt

    an instrument to deliver new-generation drugs and

    vaccines (e.g. DNA vaccines) to richly abundant

    key skin cells that reside within a tightly-defined

    location about a hair-width (~40 m) below the

    skin surface3. Immunologists have shown that these

    cells called antigen-presenting cells are very

    important in inducing strong immune responses in

    the body4. The challenge for engineers and materials

    scientists is to produce effective technologies for

    targeting these key cells just below the skin surface.

    Initially, materials scientists were slow in responding

    to this need. Up until about 15 years ago, the key

    needle-free approach for drug delivery to skin was

    the diffusive patch. Most of us are familiar with

    the diffusive patch from well-marketed nicotine

    products, but it has also had great success in

    delivering many other drugs. As the name implies,

    drug diffuses through the skins tough outer layer of

    dead cells, called the stratum corneum. This works

    well for small (< 500 Da) lipophilic molecules like

    nicotine. But many of the newer drugs and vaccines

    are much larger sometimes in the megadaltons

    range and just simply do not diffuse into the skin.

    Working collaboratively with biologists and

    clinicians, engineers have applied aerospace

    technologies to help solve this problem. In particular,

    high-speed compressible flow and other rocket-

    based technologies have been applied to deliver

    drugs and vaccines ballistically into the skin. One

    embodiment is the liquid-jet injector, which directs

    a narrow (~100 m) jet to the skin at ~100-200

    m/s that breaches the outer skin layer ballistically.

    This needle-free approach often delivers the jet

    deeper into the skin layers, making contact with the

    underlying nerve endings in the dermis so it can

    be quite painful. Liquid-jet injectors are currently

    being commercialized by BioJect. A more precise

    needle-free alternative directly descendant from

    rockets is the gene gun (otherwise called biolistics).

    In the gene gun, biological agents are reformulated

    as dry microparticles (~2 m in size) and

    accelerated in a supersonic gas jet to give sufficient

    momentum to penetrate the skin and achieve a

    pharmacological effect5. Typically, the microparticles

    impact ~1 cm2 of skin at a speed of ~600 m/s

    about the cruising speed of a Concorde aircraft.

    The method has achieved strong immune responses

    for DNA vaccines and is being commercialized by

    PowderMed, which is conducting many clinical trials

    (e.g. for influenza6).

    Looking forward, the recent explosion of micro-

    and nanotechnologies holds great promise in

    further advanced needle-free drug and vaccine

    delivery systems. For example, nanoparticles

    have been shown to diffuse through the stratum

    corneum, making them a potentially useful drug

    carrier platform. Furthermore, developments in

    microelectromechanical systems are opening up

    new opportunities to make needle-free targeting

    structures, such as micro/nanosized needle patches

    that reach the key skin cells for improved vaccines.

    Getting under the skin


    1. Lander, et al., Nature (2005) 409, 860

    2. World Health Organization, In Safety of injections, Facts & Figures Fact Sheet No. 232, (1999)

    3. Kendall, M. A. F., Vaccine (2006) 24, 4651

    4. Chen, D., et al., Expert Rev. Vaccines (2002) 1, 265

    5. Kendall, M. A. F., Shock Waves J. (2002) 12, 23

    6. Drape, R. J., et al., Vaccine (2006) 24, 4475

    Getting under the skinREFERENCES