Bubble dynamics and speed of jets for needle-free injections produced by thermocavitation.

Significance: The number of injections administered has increased dramatically worldwide due to vaccination campaigns following the COVID-19 pandemic, creating a problem of disposing of syringes and needles. Accidental needle sticks occur among medical and cleaning staff, exposing them to highly contagious diseases, such as hepatitis and human immunodeficiency virus. In addition, needle phobia may prevent adequate treatment. To overcome these problems, we propose a needle-free injector based on thermocavitation. Aim: Experimentally study the dynamics of vapor bubbles produced by thermocavitation inside a fully buried 3D fused silica chamber and the resulting high-speed jets emerging through a small nozzle made at the top of it. The injected volume can range from ∼0.1 to 2 µL per shot. We also demonstrate that these jets have the ability to penetrate agar skin phantoms and ex-vivo porcine skin. Approach: Through the use of a high-speed camera, the dynamics of liquid jets ejected from a microfluidic device were studied. Thermocavitation bubbles are generated by a continuous wave laser (1064 nm). The 3D chamber was fabricated by ultra-short pulse laser-assisted chemical etching. Penetration tests are conducted using agar gels (1%, 1.25%, 1.5%, 1.75%, and 2% concentrations) and porcine tissue as a model for human skin. Result: High-speed camera video analysis showed that the average maximum bubble wall speed is about 10 to 25 m/s for almost any combination of pump laser parameters; however, a clever design of the chamber and nozzle enables one to obtain jets with an average speed of ∼70 m/s. The expelled volume per shot (0.1 to 2 µl) can be controlled by the pump laser intensity. Our injector can deliver up to 20 shots before chamber refill. Penetration of jets into agar of different concentrations and ex-vivo porcine skin is demonstrated. Conclusions: The needle-free injectors based on thermocavitation may hold promise for commercial development, due to their cost and compactness.

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).

Delivery of insulin by jet injection: recent observations.

Medi-Ject Corporation (now Antares Pharma, Inc.) has been providing delivery devices for the needle-free administration of insulin for over 25 years. This study was one of the final steps in the development and premarket evaluation of Medi-Ject's newest needle-free system, the Medi-Jector Vision. This study was conducted to evaluate the performance of this device in the hands of experienced jet injection users in a home environment. Diabetic subjects currently using a needle-free device for the administration of their insulin were studied. Subjects used the new Medi-Jector Vision for all of their insulin administration during the course of the study. Insulin was injected on schedule and at doses consistent with their standard of practice as directed by their health care provider. All subjects were required to document each injection in a daily diary. Study subjects utilized all common insulin types (rapid, regular, intermediate, and long acting), and injections were administered in all of the common injection sites (arms, thighs, abdomen, and buttocks). Once subjects optimized the system to the most appropriate orifice size based on completeness of injection, average completeness percentages were greater than 94% for all orifice sizes. Most patients using the new Medi-Jector Vision in the home were able to manage their insulin therapy without significant complication. We conclude that the jet delivery of insulin with the new Medi-Jector Vision is well accepted by people with diabetes and offers a reliable alternative to the use of needles.

Clinical immunogenicity and tolerance studies of liquid vaccines delivered by jet-injector and a new single-use cartridge (Imule): comparison with standard syringe injection. Imule Investigators Group.

A new needleless jet-injector, Mini-Imojet, was developed that administers liquid vaccines from a single-use, pre-filled cartridge named Imule, which avoids the risk of cross-contamination. We conducted clinical trials in several settings in France and West Africa to compare the immunogenicity and tolerance of five vaccines (influenza vaccine, Vi capsular polysaccharide typhoid vaccine, tetanus toxoid vaccine, diphtheria-tetanus-whole cell pertussis vaccine, and inactivated hepatitis A vaccine) administered with the Imule system vs standard syringe technique. In each vaccine study, all subjects of either group were tested for serum antibody titres to calculate the geometrical mean titres and seroconversion rates after complete vaccination. Immediate local-reactions were noted after each injection, and local and general reactions were evaluated during a predetermined period of follow-up. When delivered by the Imule technique, all the administered vaccines were of equivalent or superior immunogenicity, compared to the syringe technique. The tolerance to vaccines injected by the Imule system was acceptable in all studies. The most frequently observed reactions were mild (e.g. minor bleeding, superficial papules, erythema and induration) and could be considered to be inherent to the injection technique. The technical and safety advantages of the Mini-Imojet/Imule system, compared to sterilizable, standard disposable or autodestruct syringes and to classical multi-dose vial jet-injectors, reinforces the interest of this new injection technique for collective immunizations.

Local anesthesia for fine-needle aspiration biopsy of palpable breast masses: the effectiveness of a jet injection system.

To determine the effectiveness of the Biojector 2000 needle-free lidocaine injection system in achieving satisfactory local anesthesia for fine-needle aspiration (FNA) of palpable breast lesions, we studied 29 female patients. Each patient served as her own control and had two FNA biopsies performed on the lesion. The first FNA biopsy was preceded by either no anesthesia, ethyl chloride cold spray, or traditional needle lidocaine injection. The second FNA was preceded by the Biojector 2000. Twenty-four patients (83%) reported that they preferred the Biojector 2000 over either no anesthesia, ethyl chloride spray, or needle and syringe lidocaine injection. The Biojector 2000 needle-free injection system is an effective and useful method of local anesthesia for FNA of palpable breast masses.

Jet-injected insulin is associated with decreased antibody production and postprandial glucose variability when compared with needle-injected insulin in gestational diabetic women.

OBJECTIVE: To elucidate the glycemic response and antibody formation in gestational diabetic women treated with insulin injected by a needle or a jet. The American Diabetes Association's position statement on jet injectors raised the concern that "insulin could be denatured as a result of forceful injection through a tiny port, which could lead to an increase in antibody formation" (Diabetes Care 11:600, 1988). However, the pharmacokinetics of jet-injected insulin suggest that it might be useful in controlling postprandial glucose levels. METHODS: We randomized 20 women with gestational diabetes mellitus (< 34 wk gestation) who required insulin to receive either jet-injected or needle-injected human NPH and regular insulin. Variables of interest were evaluated at the start of therapy, weekly until delivery, and 6-wk postpartum that included: 1) insulin antibodies in the mother and her infant, 2) HbA1c, 3) insulin dose, 4) fasting and postprandial glucose levels, and 5) subject acceptance and preference. RESULTS: Of the 10 women in the needle group, 6 developed significant insulin antibodies compared with 1 of 10 in the jet group (P < 0.001). HbA1c and insulin doses were the same in both groups. During the test meal, glucose levels in the jet group were significantly lower (P < 0.01), yet none of the women in the jet group experienced blood glucose < 70 mg/dl (3.89 mM) at 3-4 h after the meal, compared with 5 in the needle group (P < 0.001). Jet injection was associated with less variability (P < 0.001) in postprandial glucose values but slightly greater variability (P < 0.05) in fasting glucose. Jet-injected insulin was more readily accepted by subjects than needle injections. CONCLUSIONS: Jet injection is associated with a diminished antibody response and postprandial variability compared with needle-injected insulin. Thus, this warrants consideration as a therapeutic option for women with gestational diabetes mellitus and may also be applicable to nonpregnant, insulin-requiring diabetic patients.

A survey of patient preference for insulin jet injectors versus needle and syringe.

Many studies have tested the insulin absorption rate and mechanical reliability of jet injectors. However, no published papers have dealt exclusively with patient preference for this method of administering insulin over a period of years. This paper reports the results of a survey done to determine if use of a jet injector for delivering insulin has an effect on acceptance of and adherence to a regimen of multiple doses of insulin. Over the past 15 years, the authors have instructed approximately 70 patients to use various jet injectors. A questionnaire was developed and sent to 75 patients. Of these, 42 completed and returned the questionnaire. Survey results indicate that even though some problems with the injectors were identified, 70% of those responding still preferred to take insulin by jet injector.

The Medi-Jector II: efficacy and acceptability in insulin-dependent diabetic patients with and without needle phobia.

Efficacy and acceptability of the Medi-Jector II, compared with conventional syringes, was evaluated in a cross-over study (two 4-week periods) in 14 adult insulin-dependent diabetic patients. In 6 out of these 14 patients the clinical diagnosis of needle phobia was confirmed by anxiety tests for trait (45.8 +/- 12.8 (SD) versus 34.0 +/- 6.2; p less than 0.05) and state (50.3 +/- 10.9 versus 28.9 +/- 5.2, p less than 0.05). Five patients (one needle-phobic) dropped out, all for Medi-Jector-related problems. No significant differences were found in body weight, insulin dosage, and number of hypoglycaemic reactions. HbA1 after the Medi-Jector period was significantly higher than after the conventional period (9.8 +/- 1.2 (SE) versus 9.1 +/- 1.1 (SE)%; p less than 0.05). The questionnaire, evaluating the Medi-Jector, revealed poor acceptance of the device (7/9 patients' general impression being moderate or bad). The use of the Medi-Jector in comparison with conventional injections caused the patients to complain about: more immediate pain (4/9 patients), delayed pain (often: 4/9, sometimes: 2/9), more insulin leakage (6/9), more bleeding (6/9), and more haematomas (5/9). Except for 'often occurring delayed pain' (4/5 needle-phobics versus 0/4 non-needle-phobics; p less than 0.05), needle-phobic patients scored the questionnaire similarly to the other patients. We conclude that the use of the Medi-Jector II did not cause a major short-term loss of metabolic control, but that the device was not well accepted by our patients, independent of the existence of needle phobia.