The concept of needle free injection isn’t new, injectors such as the Zogenix DosePro have been on the market for several years. The principle of needle-free injection is quite straightforward – liquid drug is squirted onto the skin, through a tiny hole under such high pressure that the liquid drills through the skin and down into the tissues below. As soon as the injection stops – the hole closes up. It sounds a good idea and is helpful for people with needle phobia but it isn’t entirely pain free and the mechanics of a needle free injector aren’t trivial.
Team has a lot of accumulated knowledge about the fluidic dynamics, mechanics and practical challenges of developing needle free injectors. However what we, and the rest of the world, have never been sure of is the fate of the drug once it penetrates the skin.
Until now the most common way to see where the liquid had gone was to inject dye and look at a cross section of the tissue (see image below). This was certainly helpful but it didn’t provide a real picture of what was happening in three dimensions. Something a little more high-tech was required.
Computed Tomography (also known as CT or a CAT scan) is the technique where x-rays are taken from multiple angles around the patient and recombined by computer to create a 3D model. CT has been used in hospitals for years.
At Team we were considering how needle-free delivery could be better characterised, we wondered whether an ultrahigh resolution microCT scanner could be the answer. So we made a borrowed a £0.5m CT scanner, bought some pork, loaded x-ray opaque dye into a needle-free injector, put on some safety specs and started shooting!
The results were quite spectacular.
For the first time ever we were able to see how the drug penetrates and is distributed within the tissues. Until this point we had assumed that jet injection simply pushed liquid straight down into the tissue until it stopped, these findings show us in vivid detail how liquid almost ‘explores’ its way into the body, following multiple paths, sometimes even coming back upwards looking for the path of least resistance.
We discovered that the fluid pathway is much more complex than you might think and doesn’t necessarily always continue downwards. The liquid often bored a fairly straight initial tube before slowing down and spreading out down a number of different paths. Once within the tissue the liquid often spread in planar sheets, presumably through muscle layers and fascia. The macrostructure of different tissues will have a strong influence on the fluid path.
Here’s the video of the rotating 3D image:
It’s well known that biologic and molecular therapies are a growing part of the pharma industry’s new medicines. These new medicines will need to be delivered with ever greater precision and reliability – which in turn requires greater understanding of the interaction between drugs, devices and human physiology. microCT is just one example of a powerful tool which can help increase our understanding.
At Team we love exploring how the newest analytical techniques and technologies can be employed to increase understanding, make devices better and smooth the pathway to regulatory approval.