Gas and particle dynamics of a contoured shock tube for pre-clinical microparticle drug delivery

We investigate the gas-particle dynamics of a device designed for biological pre-clinical experiments. The device uses transonic/supersonic gas flow to accelerate microparticles such that they penetrate the outer skin layers. By using a shock tube coupled to a correctly expanded nozzle, a quasi-one-dimensional, quasi-steady flow (QSF) is produced to uniformly accelerate the microparticles. The system utilises a microparticle cassette (a diaphragm sealed container) that incorporates a jet mixing mechanism to stir the particles prior to diaphragm rupture. Pressure measurements reveal that a QSF exit period - suitable for uniformly accelerating microparticles - exists between 155 and 220 mus after diaphragm rupture. Immediately preceding the QSF period, a starting process secondary shock was shown to form with its (x,t) trajectory comparing well to theoretical estimates. To characterise the microparticle, flow particle image velocimetry experiments were conducted at the nozzle exit, using particle payloads with varying diameter (2.7-48 mu m), density (600-16,800 kg/m(3)) and mass (0.25-10 mg). The resultant microparticle velocities were temporally uniform. The experiments also show that the starting process does not significantly influence the microparticle nozzle exit velocities. The velocity distribution across the nozzle exit was also uniform for the majority of microparticle types tested. For payload masses typically used in pre-clinical drug and vaccine applications

Characteristics of a micro-biolistic system for murine immunological studies

With an advanced computational fluid dynamics (CFD) technique, we have numerically developed and examined a micro-biolistic system for delivering particles to murine target sites. The micro-particles are accelerated by a high speed flow initiated by a traveling shock wave, so that they can attain a sufficient momentum to penetrate in to the cells of interest within murine skin (or mucosa). In immunization application, powdered vaccines are directly delivered into the antigen presenting cells (APCs) within the epidermis/dermis of the murine skin with a narrow and highly controllable velocity range (e.g., 699 +/- 5.6 m/s for 1.8 mu m modeled gold particles) and a uniform spatial distribution over a diameter of similar to 4 mm target area. Key features of gas dynamics and gas-particle interaction are presented. Importantly, the particle impact velocity conditions are quantified as a function of: stand-off distance (2-15 mm), driver gas species (air/helium mixtures), particle density (1,050 kg/m(3) and 19,320 kg/m(3)) and particle size (1-5 mu m for gold particles and 10-50 mu m for less dense particles, respectively). The influential parameters-representative of immunotherapeutic (e.g., DNA vaccination) and protein (e.g., lidocaine) biolistic applications-are studied in detail