A novel use of a needle-free injection system for improved nucleic acid delivery and expression in vivo.

Transfection, a nonviral method of nucleic acid delivery, often exhibits poor efficiency in vivo. The needle-based in vivo delivery of transfection reagents can be invasive. Here, we report a noninvasive protocol for in vivo gene delivery via the needle-free MED-JET H4 MULTIJET (MJH4M) device using both "home-made" glucose-based and commercial transfection reagents. The objective of this study was to compare the relative transfection efficiencies of the needle-free system to that of the needle-based delivery method. We observed a 15-fold increase in transfection efficiency using the needle-free MJH4M device when compared to the needle-based delivery method. The highest transfection efficiency was achieved using a 5% glucose solution as the delivery vehicle.

Needle-free Mental Incisive Nerve Block:In vitro, Cadaveric, and Pilot Clinical Studies.

The present study aimed to optimize Needle-Free Liquid Jet Injection (NFLJI) for Mental Incisive Nerve Blocks (MINB) and evaluate its clinical safety and feasibility. A MINB protocol was developed and optimized by series of NFLJI experiments in soft tissue phantoms and cadavers, then validated in two pilot Randomized Controlled Trials (RCT). The NFLJI penetration depth was found to be directly proportional to the supply pressure and volume. High-pressure NFLJIs (620 kPa or above) created maximum force and total work significantly greater than needle injections. Low-pressure NFLJIs (413 kPa), however, produced results similar to those of needle injections. Additionally, high-pressure NFLJIs created jet impingement pressure and maximum jet penetration pressure higher than low-pressure NFLJIs. Pilot RCTs revealed that high-pressure NFLJI caused a high risk of discomfort (60%) and paresthesia (20%); meanwhile, low-pressure NFLJI was less likely to cause complications (0%). The preliminary success rates of MINB from cadavers using NFLJIs and needles were 83.3% and 87.5%. In comparison, those from RCTs are 60% and 70%, respectively. To conclude, NFLJI supply pressure can be adjusted to achieve effective MINB with minimal complications. Furthermore, the cadaver study and pilot RCTs confirmed the feasibility for further non-inferiority RCT.

Needle-free injection: Dental infiltration anesthesia.

This study aimed to develop an optimal Needle-Free Liquid Jet Injection (NFLJI) technique for dental infiltration anesthesia and evaluate its clinical safety and feasibility. The fluid dynamics of NFLJI in the dentoalveolar region were investigated using soft tissue phantoms supported by rigid glass. NFLJIs were performed at different incident angles and recorded using a high-speed camera. Accordingly, an optimal NFLJI for infiltration anesthesia was developed and validated on cadavers, then assessed in two pilot Randomized Controlled Trials (RCT): one for validating the safety of optimal NFLJI technique, the other for evaluating its feasibility and safety. High-speed videos showed that perpendicular NFLJIs induced significantly more regurgitation than oblique NFLJIs, which was confirmed in cadavers. Clinical trials revealed that perpendicular NFLJIs induced a high risk of bleeding (83.3%) and laceration (83.3%), whereas oblique NFLJIs induced a low risk of bleeding (33.3%) and laceration (16.7%). Moreover, the preliminary success rates of oblique NFLJIs and needle injections were both 83.3%. The recruitment took 3-5 weeks with a rate of 100%. Oblique NFLJIs could be a promising approach for dental infiltration anesthesia, causing minimal drug regurgitation with a relatively low risk of complication. The pilot RCTs confirmed the feasibility for conducting a non-inferiority RCT.

Needle-free delivery of influenza vaccine using the Med-Jet® H4 is efficient and elicits the same humoral and cellular responses as standard IM injection: A randomized trial.

BACKGROUND: Needle-free vaccine delivery systems have many potential advantages including increased vaccine compliance and decreased risk of needlestick injuries and syringe reuse. The Med-Jet® H4 is a gas-powered, auto-disabling disposable syringe jet injector. The Med-Jet family of products are currently being used in dermatology, podiatry, pain management and veterinary practices. The objectives of this study were to assess patient attitudes, time-efficiency, safety and immunogenicity of the seasonal influenza vaccine delivered by Med-Jet compared to the traditional needle-and-syringe. METHODS: A total of 80 patients were randomized 2:1:1 to receive a commercial trivalent vaccine by Med-Jet or needle injection from a single-dose or multi-dose vial. Patient attitudes were assessed pre-randomization and post-immunization. Safety data were collected for 21 days post-immunization. Efficiency of vaccine administration was measured through a time-and-motion study. Humoral and cellular responses were assessed on Days 0 and 21. RESULTS: Overall, the participants readily accepted Med-Jet vaccination despite greater frequency of transient local reactions (eg: redness, swelling) immediately following immunization. Vaccine administration took slightly longer with the Med-Jet, but this difference decreased over time. Geometric mean hemagglutination inhibition titers, seroconversion and seroprotection rates in the Med-Jet and needle groups were equivalent for all influenza strains in the vaccine. Microneutralization responses were also essentially identical. There were no significant differences between the groups in the frequency of functional CD4 + T cells, memory subset distribution or poly-functionality. CONCLUSIONS: These data suggest that the Med-Jet is an acceptable means of delivering seasonal influenza vaccine. The system was attractive to subjects, rapidly learned by skilled vaccine nurses and elicited both humoral and cellular responses that were indistinguishable from those elicited with needle injection. While other studies have assessed the humoral response to jet injection of influenza vaccine, to our knowledge, this study is the first to assess the cellular aspect of this response. (ClinTrials.gov-NCT03150537).