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By Y. Liu, and M.A.F. Kendall, Department of Engineering Science, University of Oxford, Oxford, UK
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A novel, needle-less, powdered drug delivery system is currently being
developed. It makes use of biolistics technology, where tiny particles
are injected through cell walls by a high-powered gun. The
technology provides a unique capability; it effectively delivers vaccines in
micro-particle form through the skin, into an epidermal layer where Langerhans
cells reside. By targeting these cells, an optimal immune response can be
elicited, potentially decreasing both the risk of disease and cost of protection.
In the gun, high-pressure helium gas is stored in a micro-cylinder,
and the powdered vaccine is stored in a cassette. The gun accelerates
the vaccine particles into human skin with a transient supersonic jet. To
do this, the particles must be delivered with a narrow and controllable
impact velocity range, and a wide, yet uniform spatial distribution.
A schematic of a prototype biolistics system, configured for clinical use1
Ideally, the bulk of the particle cloud should be accelerated in the quasi-steady
supersonic flow (QSSF) regime. Proper choice of system geometry,
gas species, and operating conditions can ensure that this condition
is met. Practical constraints limit the device length and the duration of
QSSF, when the particles are to be entrained. To better understand the
delivery mechanism and biological interaction, the effects of these important
parameters need to be identified and understood.
Instantaneous contour plot of the gas velocity and particle trajectories for a
silenced configuration, taken 120 ms after diaphragm rupture2
The key gas flow regimes and particle cloud trajectories of the prototype biolistics
system are shown together in the calculated space-time (x-t) diagram2
FLUENT software offers comprehensive capabilities to model the biolistics
system, from the transient gas and particle dynamics to interactions
with the skin target. The species transport equations together with the
standard k-e turbulence model are used to solve for the multi-species gas
phase flow. The coupled explicit solver is used to capture the main features
of the unsteady motion of the shock wave process. An overall second
order accuracy is satisfied both spatially and temporally. The particle
trajectory equations, in conjunction with a drag correlation and inter-phase
heat exchange, are advanced in time with the gas flow simulation. The
drag correlations proposed by Igra & Takayama (1993), which consider
unsteady effects and cover a wide range of Reynolds numbers (200 to
101,000), are implemented through user-defined functions (UDFs).
Through the modeling efforts, the FLUENT simulations have allowed
for the evaluation of key parameters, the visualization of different designs,
and the gathering of new insights into the biolistics system. Simulations
of the whole prototype biolistics system, as well as of the key components,
have shown an excellent agreement with the static pressure measurements,
Pitot probe survey, and images made using Doppler global
velocimetry (DGV) and particle image velocimetry (PIV).1,2 A space-time
diagram that shows different gas flow regimes and particle cloud trajectories
can be used to illustrate the performance of the prototype. The diagram
demonstrates that the particles are accelerated to the nozzle exit, avoiding
the starting process1 and the reflected expansion wave, and thereby
remaining in the QSSF regime, as desired.
References:
- M.A.F. Kendall, The Delivery of Particulate Vaccines and Drugs to Human Skin with a
Practical, Hand-held Shock Tube-based System, Shock Waves Journal, 12(1), pp.22-
30, 2002.
- Y. Liu, M.A.F. Kendall, N.K. Truong, and B.J. Bellhouse, Numerical and Experimental
Analysis of a High Speed Needle-free Powdered Vaccines Delivery Device, AIAA-2002-
2807, Proc. 20th AIAA Applied Aerodynamics Conference, St. Louis, MO, USA,
2002.
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