Microneedle Assisted Micro-Particle Delivery from Gene Guns: Experiments Using Skin-Mimicking Agarose Gel

Abstract

A set of laboratory experiments has been carried out to determine if micro‐needles (MNs) can enhance penetration depths of high‐speed micro‐particles delivered by a type of gene gun. The micro‐particles were fired into a model target material, agarose gel, which was prepared to mimic the viscoelastic properties of porcine skin. The agarose gel was chosen as a model target as it can be prepared as a homogeneous and transparent medium with controllable and reproducible properties allowing accurate determination of penetration depths. Insertions of various MNs into gels have been analysed to show that the length of the holes increases with an increase in the agarose concentration. The penetration depths of micro‐particle were analysed in relation to a number of variables, namely the operating pressure, the particle size, the size of a mesh used for particle separation and the MN dimensions. The results suggest that the penetration depths increase with an increase of the mesh pore size, because of the passage of large agglomerates. As these particles seem to damage the target surface, then smaller mesh sizes are recommended; here, a mesh with a pore size of 178 μm was used for the majority of the experiments. The operating pressure provides a positive effect on the penetration depth, that is it increases as pressure is increased. Further, as expected, an application of MNs maximises the micro‐particle penetration depth. The maximum penetration depth is found to increase as the lengths of the MNs increase, for example it is found to be 1272 ± 42, 1009 ± 49 and 656 ± 85 μm at 4.5 bar pressure for spherical micro‐particles of 18 ± 7 μm diameter when we used MNs of 1500, 1200 and 750 μm length, respectively. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:613–627, 2014

Microneedle-assisted microparticle delivery by gene guns: experiments and modeling on the effects of particle characteristics

“…In principle, reduction of the operation pressure in the gene guns (Yoshida et al, 1997;Uchida et al 2009) and particle size can minimize the cell/tissue damage but these tend to decrease the particle momentum and, hence, the penetration depths of the microparticles in the tissue. In order to resolve these issues, a series of experiments that combine solid microneedles (MNs) with an in-house microparticle delivery system (see Figure 1) has been reported recently by Zhang et al (2013aZhang et al ( , 2014.…”

“…In this case, the microparticles can penetrate with less resistance into the skin through the holes and further achieve an enhanced penetration depth to allow gene transfection in deeper tissue. Zhang et al (2014) have used the experimental setup of MN-assisted microparticle delivery to fire biocompatible stainless steel microparticles having an average diameter of 18 mm into a skin mimicking agarose gel. Their results have shown that a number of microparticles penetrate through the holes and achieve a considerable increase in the maximum penetration depth, e.g.…”

“…The overall process of MN-assisted transdermal microparticle delivery from gene guns consists of three main stages, which are the acceleration, separation and deceleration stages (Zhang et al, 2013a(Zhang et al, , 2014. These stages are identified in Figure 1.…”

“…Previously, Zhang et al (2014) used an experimental rig (Figure 1) to deliver stainless steel microparticles into a skin mimicking agarose gel so as to demonstrate the feasibility of MN-assisted microparticle delivery. The results have shown that an enhanced penetration depth of microparticles inside the agarose gel can be achieved using MN-assisted microparticle delivery at a much lower injection pressure compared to typical gene guns.…”

“…Recently, O'Brien & Lummis (2011) reported that the penetration depth of golden microparticles of 1 mm diameter in mouse ear Figure 1. A schematic diagram of the experimental rig for the MN-assisted microparticle delivery system (Zhang et al, 2014). tissue is 50 ± 11 mm when the Helios gene gun is used at an operating pressure of 5.1 bar (75 psi).…”