fast liquid jets are investigated for use as a needle-free drug delivery system into an elastic tissue such as skin. Using smaller jet diameters in a repetitive regime can mitigate bruising and pain associated with current injectors. in this study, we aim to unravel the potential of the method to deliver liquids into biological tissues having higher elasticity than healthy skin (i.e >60 kPa). To address this challenge, we have implemented a laser-based jetting system capable of generating supersonic liquid microjets in a repetitive regime. We provide insights on the penetration of microjets into hydrogel samples with elastic modulus ranging from 16 kPa to 0.5 MPa. The unprecedented speeds of injection (>680 m/s) together with a newly introduced repetitive regime opens possibilities for usage in needle-free drug administration into materials with elasticity covering the wide spectrum of biological soft tissues like blood vessels, all skin layers, scarred or dried skin or tumors.Development of needle-free delivery systems for distribution of medicines was listed as one of the grand challenges in global health 1 . The goal is to reduce contaminated waste, mitigate the risk of disease spreading or to avoid needle-stick accidents. Fast liquid jets carry spatially confined kinetic energy that can penetrate into a tissue 2 . Motivation for this work ranges from the development of needle-free transdermal drug injectors 3-9 , "liquid scalpel" for soft tissue dissecting 10-12 or devices for gene delivery [13][14][15] . The main advantage lies in the smaller extent of collateral damage caused to the tissue, superior lateral precision and addressability of certain depths 16 .The use of currently available jet injectors is associated with pain and bruising which originates from the relatively large injection depth and volume 4 . This can be addressed by injecting smaller diameter jets in repetitive regime thus compensating for the smaller volume of each jet by its multiplicity. In the context of needle-free drug delivery, this strategy was first implemented by Arora 4 using a piezo actuator system 17 . The Arora study 4 showed that in vivo injection in rats minimized the collateral damage and provided sufficient dosage of insulin. The same technology was used by Römgens et al. 3 who reported a delivery efficiency through the first skin layer (epidermis) as high as 90%. Jets were mostly stopped by the reticular dermis and reached the hypodermis with the efficiency of only 12%. With regard to the diagram presented by Rodríguez et al. 18 we can claim, that such shallow penetration prevents this technology from delivering a drug aimed to reach the hypodermis or muscle tissue.
Jet injection devices have been studied and developed for transdermal drug delivery to avoid the use of needles. Due to bulky actuation mechanisms, they are limited to body areas that...
Needle-free jet injection enables the delivery of drugs into skin or soft tissue by puncturing them with a high-velocity liquid jet. However, precise and efficient drug delivery requires generating such liquid jets with both a controlled velocity and a high throughput, which remains challenging with current spring-and gas-actuated jet injectors. Here, we propose a depth-controlled and high-throughput injection method by adapting laser-induced forward transfer (LIFT), a high-resolution two-dimensional printing technique, for direct three-dimensional liquid delivery into soft tissues.The velocity of thin liquid jets is laser actuated from 10 to 85 m/s so that doses as small as 10 pL, not achievable with other injectors, are injected at a 1 Hz repetition rate into a 300 μm thick soft gelatin substrate with a 25 μm depth precision and 12 μm lateral resolution. We further investigate the potential of this liquid delivery technique as a direct three-dimensional cell-delivery vehicle and show that depth-controlled particle delivery requires high-delivery efficiency. Our direct three-dimensional liquid delivery system opens up more possibilities for pinpoint drug delivery in soft tissues or tissue-engineered constructs.
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