<title>Analysis of microparticle penetration into human and porcine skin: non-invasive imaging with multiphoton excitation microscopy</title>

Abstract

At the University of Oxford and PowderJect Pharmaceuticals plc, a unique form of needle-free injection technology has been developed. Powdered vaccines and drugs in micro-particle form are accelerated in a high-speed gas flow to sufficient velocity to enter the skin, subsequently achieving a pharmaceutical effect. To optimize the delivery of vaccines and drugs with this method a detailed understanding of the interactive processes that occur between the microparticles and the skin is necessary. Investigations to date of micro-particle delivery into excised human and animal tissue have involved image analyses of histology sections. In the present study, a series of investigations were conducted on excised human and porcine skin using the technique of Multi-Photon fluorescence excitation Microscopy (MPM) to image particles and skin structures post-penetration. Micro-particles of various size and composition were imaged with infrared laser excitation. Three-dimensional images of stratum corneum and epidermal cell deformation due to micro-particle penetration were obtained. Measurements of micro-particle penetration depth taken from z-scan image stacks were used to successfully quantify micro-particle distribution within the skin, without invasively disrupting the skin target. This study has shown that MPM has great potential for the non-invasive imaging of particleskin interactive processes that occur with the transdermal delivery of powdered micro-particle vaccines and drugs.

Numerical simulation of heat transfer from a transonic jet impinging on skin for needle-free powdered drug and vaccine delivery

“…Operation commences with the opening of the helium micro-cylinder, and the subsequent diaphragm rupture initiates a transonic gas flow of accelerating particles that penetrate the outer layer of the skin target. The ballistic interaction of particles with the human, porcine and murine skin targets has been examined experimentally and analytically [4,[9][10][11][12][13][14]. However, investigations of the impinging gas jet interaction with the skin have been limited to surface deflections from the impinging pressure [15].…”

Design and commissioning of a directly coupled in-vivo multiphoton microscope for skin imaging in humans and large animals

“…In recent studies we reported the application of multiphoton microscopy to image powdered micro-particles delivered to excised skin of human and porcine models 18,19 . These investigations revealed the technique's utility to acquire detailed qualitative and quantitative data pertaining to the dynamics of powdered vaccine delivery.…”