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Title: Application of microneedles to enhance delivery of micro-particles from gene guns
Authors: Zhang, Dongwei
Keywords: Gene guns
Micro-particles
Microneedles
Agarose gel
Porcine Skin
Modelling
Issue Date: 2013
Publisher: © Dongwei Zhang
Abstract: Gene gun assisted micro-particle delivery system is an excellent method for the delivery of DNA into target tissue so as to carry out gene transfection in the target cells. The gene gun is primarily a particle accelerator which accelerates DNA-coated micro-particles to sufficient velocities to breach the target layer enabling the micro-particles to penetrate to a desired depth and target the cells of interest to achieve gene transfer. However, an inevitable problem in this process is the tissue/cell damage due to the impaction of the pressurized gas and micro-particles on the target. The purpose of this research is developing a new conceptual system which improves the penetration depth of micro-particles at less imposed pressure and particle injection velocity. This is achieved by applying a microneedle array and ground slide in the gene gun system, thus a study involving microneedle assisted micro-particle delivery is conducted in this work. Microneedle array is used to create holes in the target which allows a number of micro-particles to penetrate through the skin which enhances the penetration depth inside target. The ground slide is used to load a pellet of the micro-particles and prevent the pressurized gas to avoid the impaction on the target. The operation principle is that the pellet is attached to ground slide which is accelerated to a sufficient velocity by the pressurized gas. The pellet is released from the ground slide which separates into individual micro-particles by a mesh and penetrates to a desired depth inside the target. An experimental rig to study various aspects of microneedle assisted micro-particle delivery is designed in this PhD research. The passage percentage of the micro-particles and size of the separated micro-particles are analysed in relation to the operating pressure, mesh pore size and Polyvinylpyrrolidone (PVP) concentration to verify the applicability of this system for the micro-particle delivery. The results have shown that the passage percentage increases from an increase in the mesh pore size and operating pressure and a decrease in PVP concentration. A mesh pore size of 178 μm and pellet PVP concentration of 40 mg/ml were used for the bulk of the experiments in this study as these seem to provide higher passage percentage and the narrow size distribution of the separated micro-particles. In addition, the velocity of the ground slide is detected by the photoelectric sensor and shown that it increases from an increase in operating pressure and reaches 148 m/s at 6 bar pressure, A further analysis in the penetration depths of the micro-particles to determine whether they achieve enhanced penetration depths inside the target after using microneedles is carried out. A skin mimicked agarose gel is obtained from comparing the viscoelastic properties of various concentration of agarose gel in comparison with the porcine skin, which is assumed to mimic the human skin. These experiments are used to relate the micro-particle penetration depth with the operating pressure, microneedle length and particle size. In addition, a theoretical model is developed based on the experimental data to simulate the microneedle assisted micro-particle delivery which provide further understanding of the microneedle assisted micro-particle delivery. The developed model was used to analyse the penetration depth of micro-particles in relation to the operation pressure, target properties, microneedle length and particle size and density. The modelling results were compared with the experimental results to verify the feasibility of the microneedle assisted micro-particle delivery for micro-particles delivery. As expected, both experimental and theoretical results show that the micro-particles achieve an enhanced penetration depth inside target. The maximum penetration depth of micro-particles is increased from an increase in operating pressure, microneedle length, particle size and density.
Description: A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.
Sponsor: Loughborough University
URI: https://dspace.lboro.ac.uk/2134/13744
Appears in Collections:PhD Theses (Chemical Engineering)

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