Fundamental mechanisms of drug delivery by jet injection: Basis for the development of a painless microject injector

Conventional needles are the primary method for the delivery of macromolecular drugs such as insulin and vaccines. However, patient compliance with needle injections is low, especially for chronic prescriptions. In addition, concern about the spread of disease around the world from needlestick injuries and the reuse of needles calls for the use of needle-free drug delivery methods.; Jet injection is a needle-free drug delivery method which employs a high-speed stream of fluid that impacts the skin and delivers drugs intradermally, subcutaneously, or intramuscularly often with quicker absorption and greater immune response from vaccines than by needle injections. Although jet injectors have been commercially used for vaccinations and insulin delivery since the 1940s, little had been known about the mechanism of jet injection or the parameters which control it. Occasional pain and variability associated with injections may have limited their widespread use. My research has focused on determining the overall mechanisms of drug delivery by jet injection in order to identify design parameters for a new generation of painless jet injectors.; The overall mechanism and controlling parameters of drug delivery were determined through experiments quantifying fluid penetration into human skin as a function of jet and material parameters, analyzing jet penetration into a model soft material, and measuring jet-impingement erosion of skin. Jet injection occurs by jet-induced erosion of skin followed by fluid dispersion into the skin. The quantity and depth of penetration are controlled by the jet velocity and nozzle diameter as well as the Young's modulus of the skin. The power of the jet, which described the effects of both jet velocity and nozzle diameter, was identified as a critical parameter for drug delivery due to its linear relationship with the quantity of delivery into skin. A predictive model of the erosion of the skin was developed that incorporates jet and skin properties as the first major step in mathematically predicting the depth and quantity of drug delivery by jet injection. As a result of these mechanistic studies guidelines were developed for a painless jet injector and implemented in a pulsed microjet injector for shallow intradermal delivery.