OPINION

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 | m.kendall@uq.edu.au

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. Let’s 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 µm) 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 skin’s 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 µm) 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 µm 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

REFERENCES

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