Laser-induced liquid micro-jets for drug delivery

Jet injection devices have been studied and developed for transdermal drug delivery to avoid the use of needles. Such contact-less devices provide several advantages such as better dose control, lateral and depth localisation, lower collateral damage than the needles and reportedly higher efficacy of some treatments. The administration is based on a fast stream of liquid which yields sufficient power to penetrate deep into soft body tissue. This thesis describes laser-based jet injection technology where the actuation scheme exploits optical cavitation in a capillary nozzle.

We present several advancements in the system design. First, I optimised the working conditions for the generation of supersonic liquid microjets in a repetitive regime. The use of multiple jets with smaller diameters allows keeping proper dosing while mitigating damage to the tissue. Second, we introduce a novel laser-pulse distribution scheme by using a multimode optical fibre for light delivery in a capillary which allows a liquid delivery device design to be thin and long (e.g. flexible and 30 cm long with 1.2 mm outer diameter) compatible with minimally invasive surgical procedures. This innovation step opens up the possibility of the jet injection to inner body organs or other hardy accessible targets. I also found a convenient laser source in the near-infrared spectrum, which circumvents the need for sample reformulation and allows the generation of fast (60 kPa). I provide insights on the penetration of microjets into hydrogel samples with elastic modulus ranging from 16 kPa to 0.5 MPa. Our study suggests possible administration into materials with elasticity covering the broad spectrum of biological soft tissues like blood vessels, all skin layers, scarred or dried skin or tumours. I also show a superior injection efficiency with the fibre-based illumination system, which is because only focused part of the jet is propelled from the nozzle.

Intense laser illumination of a drug raises the question of potential degradation of the product and hence the biocompatibility of the delivered product. I evaluated the integrity of several molecules (Lidocaine, 5-Aminolevulinic acid, rabbit immunoglobulin, DNA) and their functionality after delivery with the injection device. Our tests showed no degradation, and therefore we can conclude that this technology can be a promising route of local drug administration.