Hydrodynamics of needle-free jet injections

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Although traditional hypodermic needle injections are currently used across the globe for the delivery of therapeutic drugs and vaccines, their use is associated with needle-stick injuries, cross-contamination, needle phobia, sharps waste management, etc. The annual cost of needle-stick injuries for the US alone is billions of dollars. Needle-free jet injections (NFJIs) are one of the leading alternatives to needle-based injections, in which a narrow jet of the drug is generated with a diameter of O(100) microns and a jet speed of O(100) m/s; this liquid jet punctures the skin and delivers the drug inside the skin tissue within O(10) ms. Moreover, improved immune responses for intradermal drug delivery of DNA vaccines have triggered research in this area. Although the idea of fast and easy drug delivery via jet injector seems fascinating, their use is limited by insufficient drug delivery, cross-contamination, pain, bruises during injection, etc.

My dissertation work is based on leveraging the hydrodynamics of NFJIs to achieve complete (~100%) drug delivery inside the skin within the dermis region. We use a spring-powered jet injector with a spring constant of 63 lb/in which generates a stagnation pressure of O(10) MPa, which generates liquid jets with a force enough to puncture the top layer and deposit the drug inside the skin. We investigated the effects of a wide range of parameters associated with the drug properties, design of the nozzle and the jet injector, and jet actuation on the delivery efficiency and the drug dispersion within the skin. Using various skin models, we comprehensively studied the effect of these parameters on the delivery percentage and dispersion of liquid inside the skin.

Using a commercial spring-powered jet injector, we ultimately achieved nearly complete delivery by identifying a range of applied loads (i.e., the force with which the injector is pressed onto the skin) during the injection. Moreover, drug dispersion was observed to depend on the liquid properties, standoff distance, and nozzle dimensions. Through an extensive study, we showed hydrogels are poor skin models and we propose poroelastic sponge-gel composites as a better skin model. We also addressed the effect of air pockets in pre-filled nozzles on the efficiency and effectiveness of drug delivery via jet injectors. Further, we studied the feasibility of innovative techniques such as spark-induced and laser-induced jetting for precise low-volume drug delivery via jet injection technique. The results of our study showed jet injectors to be an excellent candidate as a drug delivery device for a wide range of liquid drugs with significant improvement in performance. We believe that this work can help circumvent the current shortcomings of jet injectors and improve the outlook for needle-free intradermal drug delivery. This is especially relevant for resource-limited and developing countries that do not have the infrastructure for large volume sharps waste. Furthermore, it is highly promising for the emergence of nucleic acid vaccines for future pandemics.

Embargo status: Restricted until 09/2023. To request the author grant access, click on the PDF link to the left.

Needle-free, Jet injections, Drug delivery, Intradermal, Injections, Hydrogel