Needle-free Jet Injection Research Articles

Therapeutic Performance of Needle Injection Versus Needle-Free Jet Injector System for Polynucleotide Filler in Skin Rejuvenation.

Polynucleotide (PN) filler often causes pain and can lead to delivery inaccuracies when applied via intradermal injection using a traditional needle. To evaluate the efficacy of treatment and the pain during the procedure using conventional needle injection versus a needle-free jet system for intradermal PN filler application. In this split-face clinical trial, 10 Korean subjects were enrolled. Each subject received an intradermal injection of PN filler on one side of the face and a needle-free jet injection using CureJet on the other side. Assessments included global and 3D skin imaging at each visit. Pain intensity was evaluated using visual analogue scale (VAS) scores during the injection. Additionally, patient satisfaction and adverse events were documented. Findings revealed that Global Aesthetic Improvement Scale scores and patient satisfaction were significantly higher with the CureJet compared to the needle injection method. VAS scores were notably lower on the CureJet side. Improvements in both pore and wrinkle indices were observed from baseline, with a more pronounced improvement rate on the CureJet side compared to the needle injection side. Needle-free injection of PN for aging skin was found to be effective in enhancing pore and wrinkle improvement, while reducing associated discomfort.

Thermocavitation in gold-coated microchannels for needle-free jet injection

Continuous-wave lasers generated bubbles in microfluidic channels are proposed for applications such as needle-free jet injection due to their small size and affordable price of these lasers. However, water is transparent in the visible and near-IR regime, where the affordable diode lasers operate. Therefore, a dye is required for absorption, which is often unwanted in thermocavitation applications, such as vaccines or cosmetics. In this work, we explore a different mechanism of the absorption of optical energy. The microfluidic channel wall is partially covered with a thin gold layer, which absorbs light from a blue laser diode. This surface absorption is compared with the conventional volumetric absorption by a red dye. The results show that this surface absorption can be used to generate bubbles without the requirement of a dye. However, the generated bubbles are smaller and grow slower when compared to the dye-generated bubbles. Furthermore, heat dissipation in the glass channel walls affects the overall efficiency. Finally, degradation of the gold layer over time reduces the reproducibility and limits its lifetime. Further experiments and simulations are proposed to potentially solve these problems and optimize the bubble formation. Our findings can inform the design and operation of microfluidic devices used in phase transition experiments and other cavitation phenomena, such as jet injectors or liquid dispensing for bio-engineering.

Effect of orientation angle for needle-free jet injection

In this paper, we report on the delivery efficiency of needle-free jet injections using injectors with typical jet speed vj≈140m/s, orifice diameter do=157μm, and volume V=0.1 mL. The target substrates were either hydrogel tissue phantoms or porcine tissues combined with excised human skin. The novelty of this study is two-fold: First, we investigate the influence of injection angle relative to the skin surface, and second, we also study the influence of the jet path relative to the orientation of muscle fibers. While most commercial jet injectors employ a fitting that would render the device normal to the skin surface, recent studies have proposed oblique injections, which may be beneficial for intradermal or subcutaneous tissue injection. Furthermore, for deeper intramuscular injections, we propose that an angled jet path taking the muscle fiber orientation into account may result in a bolus or dispersion zone that is conducive to increased cellular uptake of the drug.

Needle-free jet injector treatment with bleomycin is efficacious in patients with severe keloids: a randomized, double-blind, placebo-controlled trial.

Severe keloids are difficult to treat. Corticosteroid injections with needles are painful and associated with frequent recurrences. Therefore, more effective, safe and patient friendly alternative treatments are urgently needed. To assess the efficacy, tolerability, and patient satisfaction of intralesional bleomycin treatment using a needle-free electronic pneumatic jet injector (EPI) in severe keloids. Patients with severe keloids were included in this double-blind, randomized placebo-controlled trial with split-lesion design. Three EPI treatments with bleomycin or saline, were administered every four weeks in respectively the intervention and control side. Outcome measures were change in scar volume assessed by 3D-imaging, Patient and Observer Scar Assessment Scale (POSAS), skin perfusion with laser speckle contrast imaging (LSCI), spilled volume, procedure related pain, adverse events, and patient satisfaction. Fourteen patients (9 female, 5 men) were included. The estimated mean keloid volume was significantly reduced with 20% after EPI-assisted bleomycin, compared to a slight increase of 3% in the control side (p<0.01). The estimated mean POSAS patient and observer scores decreased with respectively 26% and 28% (p = 0.02; p = 0.03). LSCI showed no significant change in perfusion. EPI treatment was preferred over previous needle injections in 85% of patients. The estimated mean spilled volume after EPI was around 50%, and NRS pain scores were moderate. Adverse events included bruising, hyperpigmentation, and transient superficial necrosis. Three EPI-assisted bleomycin treatments are efficacious and well-tolerated in severe keloids. Moreover, EPI treatment was preferred by most patients and may serve as a patient-friendly alternative treatment.

Hydrodynamics of a dual-orifice needle-free jet injector

In the recent literature, it has been shown that an enhanced, multi-faceted, balanced immune response can be generated using a combined intradermal (ID) and intramuscular (IM) delivery of vaccines, especially for novel DNA vaccines. However, needle-based injection for a combined ID/IM delivery may require separate injections, which may prove to be time consuming, and impractical for mass immunizations. In contrast, a novel multi-orifice jet injector could be used to deliver drugs at multiple penetration depths simultaneously, which may provide advantages such as ease of operation, elimination of sharps, and short injection timeframe (O (10 m)).Here, we consider a dual-orifice geometry with both a wide orifice (200 μm–400 μm) for IM drug delivery and a narrow orifice (100 μm) for ID drug delivery. Using numerical simulations, we found that, at a fixed upstream pressure, jet velocities through wide and narrow orifices do not vary significantly for low-viscosity fluids (≲4%). However, it was previously hypothesized that the jet power, Pj=π8ρdj2vj3, is a more appropriate parameter to characterize tissue penetration depth. Thus, the jet power could vary by a factor of ∼10, yielding different depths for the two orifices. Using non-dimensional analysis via Euler (Eu) and Reynolds (Re) numbers, we characterize the role of orifice geometry and driving pressure, to generate geometry-specific correlations in the Eu–Re parameter space to estimate the jet velocity and pressure losses. We also elucidate the orifice size ratios that are best suited for fractional doses of ∼100 μL to intradermal tissue from a total injection of 1 ml.Preliminary experiments to visualize the penetration of wide and narrow jet streams into gelatin and pork substrates showed that the wide jet stream leads to substantially greater penetration depth than the narrow jet stream. In summary, we provide the initial feasibility of simultaneous delivery of a drug to multiple penetration depths from the same injection cartridge using the needle-free jet injection technique.

Delivery of Experimental mRNA Vaccine Encoding the RBD of SARS-CoV-2 by Jet Injection.

We studied a needle-free jet injection delivery of an experimental mRNA vaccine encoding the receptor-binding domain of the SARS-CoV-2 S protein (mRNA-RBD). Immunization of BALB/c mice with mRNA-RBD by a needle-free jet injector induced high levels of antibodies with virus-neutralizing activity and a virus-specific T-cell response. The immune response was low in the group of mice that received intramuscular injection of mRNA-RBD. The effectiveness of this simple and safe method of mRNA delivering has been demonstrated. Thus, jet injection of mRNA vaccine can be a good alternative to lipid nanoparticles.

Needle-Free Jet Injection of Poly-(Lactic Acid) for Atrophic Acne Scars: Literature Review and Report of Clinical Cases.

Acne scars, particularly atrophic ones, present a persistent challenge in cosmetic medicine and surgery, requiring extended and multifaceted treatment approaches. Poly-(lactic acid) injectable fillers show promise in managing atrophic acne scars by stimulating collagen synthesis. However, the utilization of needle-free injectors for delivering poly-(lactic acid) into scars remains an area requiring further exploration. In this article, a summary of the latest advancements in needle-free jet injectors is provided, specifically highlighting the variations in jet-producing mechanisms. This summary emphasizes the differences in how these mechanisms operate, offering insights into the evolving technology behind needle-free injection systems. The literature review revealed documented cases focusing on treating atrophic acne scars using intralesional poly-(lactic acid) injections. The results of these clinical studies could be supported by separate in vitro and animal studies, elucidating the feasible pathways through which this treatment operates. However, there is limited information on the use of needle-free jet injectors for the intradermal delivery of poly-(lactic acid). Clinical cases of atrophic acne scar treatment are presented to explore this novel treatment concept, the needle-free delivery of poly-(lactic acid) using a jet pressure-based injector. The treatment demonstrated efficacy with minimal adverse effects, suggesting its potential for scar treatment. The clinical efficacy was supported by histological evidence obtained from cadaver skin, demonstrating an even distribution of injected particles in all layers of the dermis. In conclusion, we suggest that novel needle-free injectors offer advantages in precision and reduce patient discomfort, contributing to scar improvement and skin rejuvenation. Further comprehensive studies are warranted to substantiate these findings and ascertain the efficacy of this approach in scar treatment on a larger scale.

Needle-Free Jet Injector-Assisted Triamcinolone Treatment of Keloids and Hypertrophic Scars is Effective and Well Tolerated in Children.

Keloids and hypertrophic scars can cause severe pain, pruritus, and psychological distress. Conventional intralesional corticosteroid treatment with needle injections remains challenging, especially in children with needle phobia. We aimed to evaluate the effectiveness, tolerability, and patient satisfaction of intralesional treatment with triamcinolone acetonide using a needle-free electronic pneumatic jet injector in children with keloids and hypertrophic scars. A retrospective study was performed in children with keloids and hypertrophic scars who received intralesional triamcinolone acetonide treatments using an electronic pneumatic jet injector. Effectiveness was evaluated using the Patient and Observer Scar Assessment Scale and Global Aesthetic Improvement Score at follow-up versus baseline. Tolerability was assessed with reported adverse effects and injection-related pain using a visual analog scale. Satisfaction questionnaires were used to evaluate treatment-related patient satisfaction. Six female patients and five male patients aged 5-17 years, with a total of >118 keloids or hypertrophic scars were included. Electronic pneumatic jet injector treatment led to a significant reduction in the total Patient and Observer Scar Assessment Scale observer and patient scores compared with baseline, with a median reduction of 28.9% and 23.8%, respectively (p = 0.005; p = 0.009). Median visual analog scale pain scores for electronic pneumatic jet injector treatment were significantly lower compared with needle injections, 3.0 versus 7.0, respectively (p = 0.027). No severe adverse effects were reported. Overall, 6 patients were 'satisfied' and five patients were 'very satisfied' with the treatment. Electronic pneumatic jet injector-assisted intralesional triamcinolone acetonide is an effective and well-tolerated treatment for keloids and hypertrophic scars in children. It should be considered as an alternative non-traumatic delivery method, especially in children with needle phobia or severe pain during previous needle injections.

Large volume subcutaneous delivery using multi-orifice jet injection

Needle-free jet injection is an alternative drug delivery technique that uses the liquid drug itself to penetrate through the skin. This technology is not only a promising alternative to hypodermic needles but also has the potential to replace intravenous delivery with rapid, needle-free subcutaneous delivery for large-volume treatments. In this work we propose a parallelised, ‘multi-orifice’ approach to overcome the volume constraints of subcutaneous tissue. We present a prototype multi-orifice nozzle with up to seven orifices and use this nozzle to perform injections into samples of ex vivo porcine tissue. These injections demonstrated the rapid (<0.15 s) delivery of up to 2 mL into the tissue using both three and seven orifices. Delivery success (measured as the percentage of fluid deposited in the tissue relative to the total volume that left the device) was very similar when using three versus seven injection orifices. A computational fluid dynamic model of multi-orifice jet injection is also presented. This model predicts that jet production is largely unaffected as the spacing between orifices is changed from 3 mm to 48 mm. This finding is supported by measurements of the speed, volume, and shape of the jets produced by the prototype nozzle that showed very similar jets were produced through all seven orifices. These findings demonstrate the feasibility of multi-orifice jet injection for needle-free delivery of large volumes. This promising technique has the potential to improve patient experience and reduce healthcare costs in large volume parenteral delivery applications.

Systematic Review: Teknologi Needle Free Jet Injection Insulin (NFJI) Efektif Mengontrol Konsentrasi Glukosa Pada Penderita Diabetes Melitus Tipe 2

Needle-free jet injection (NFJI) is a needleless method for insulin delivery in type 2 diabetes mellitus (T2DM) patients. This study evaluates NFJI's effectiveness in controlling blood glucose. In this study, we conducted a systematic review following the PRISMA guidelines, searching six databases (EBSCO Host, ProQuest, PubMed, ScienceDirect, Scopus, and Web of Science). The search yielded a total of 379 articles. We used the following keywords: "Jet injection," "Injection Ject," "Needle-Free Injection," "Insulin," "Diabetes Mellitus Type 2," "Diabetes Type 2," "Type 2 Diabetes," and "Blood Glucose" to identify relevant studies. The aim was to investigate the effectiveness of insulin jet NFJI in controlling blood glucose levels in T2DM patients. We assessed the risk of bias using the Joanna Briggs Institute (JBI) critical appraisal tools checklist. Out of the 379 articles identified, only seven met the inclusion criteria. Among these, six articles employed the Randomized Controlled Trial (RCT) method, while one article used a quasi-experimental design. Respondents in the study consisted of T2DM patients who were divided into two research groups: the intervention group and the control group. The results indicated a significant difference in blood glucose control values between the two groups. NFJI insulin method significantly improves glucose control. It offers advantages like painless, scar-free, low drug preparation, reusability, ease of use, and minimal disease transmission. Recommended for long-term T2DM treatment.

Needle-free electronically-controlled jet injector treatment with bleomycin and lidocaine is effective and well-tolerated in patients with recalcitrant keloids.

The treatment of recalcitrant keloids is challenging. Although intralesional bleomycin using conventional needle injectors (CNI) is effective, it has important drawbacks, such as the need for repetitive and painful injections. Therefore, we aimed to evaluate the effectiveness, tolerability and patient satisfaction of intralesional bleomycin with lidocaine administered with a needle-free electronically-controlled pneumatic jet-injector (EPI) in recalcitrant keloids. This retrospective study included patients with recalcitrant keloids who had received three intralesional EPI-assisted treatments with bleomycin and lidocaine. Effectiveness was assessed using the Patient and Observer Scar Assessment Scale (POSAS) at baseline and four to six weeks after the third treatment. Additionally, treatment related pain scores numeric rating scale, adverse effects, patient satisfaction and Global Aesthetic Improvement Scale (GAIS) were assessed. Fifteen patients with a total of >148 recalcitrant keloids were included. The median total POSAS physician- and patient-scores were respectively 40 and 41 at baseline, and reduced with respectively 7 and 6-points at follow-up ( p < 0.001; p < 0.001). The median pain scores during EPI-assisted injections were significantly lower compared to CNI-assistant injections, (2.5 vs. 7.0, respectively ( p < 0.001)). Adverse effects were mild. Overall, patients were "satisfied" or "very satisfied" with the treatments (14/15, 93.3%). The GAIS was "very improved" in one patient, "improved" in nine patients and "unaltered" in four patients. EPI-assisted treatment with bleomycin and lidocaine is an effective, well tolerated, patient-friendly alternative for CNI in patients with recalcitrant keloid scars. Randomized controlled trials are warranted to confirm our findings and improve the clinical management of recalcitrant keloids.

Conceptualisation of a novel electromechanical system for small-volume needle-free jet injection

Needle-free jet injectors are minimally invasive drug delivery systems that utilise high-velocity microjets (∼100 m/s) created by pressurising the liquid drug through a micronozzle (50–300 µm in diameter). Most of the current commercially available jet injectors use a mechanical power possessed by a compressed spring or air to pressurise the fluid inside the injection chamber to deliver the liquid drug (typically ∼100 µL in volume) into the skin matrix. However, they cannot be utilised for achieving shallow penetration depths as they lack dynamic control that can shape the real-time microjet characteristics. Recently, electrically or optically powered jet injection systems are being developed to achieve shallow penetration depth by small-volume (<5 μL) injections. However, they require complex system and have a limited injection frequency (maximum reported value is 16 Hz). Herein, we propose a novel electro-mechanical jet injection system, where a mechanically actuated source pressurises the fluid inside the injection chamber and an electrically actuated system controls the characteristics of the propelled microjet. A computational model was developed to prove the feasibility of the proposed system, and the obtained results showed that the proposed system could produce stable small-volume microjets at about 100 Hz frequency that could be utilised for drug delivery applications.

Measurement of Blood Dilution during Lancet-Free Blood Sampling.

In this paper, we report on a fluorescent and colorimetric system for measuring the dilution of capillary blood released by a needle-free jet injector. Jet injection uses a high-speed liquid jet to penetrate tissue, and in the process can release capillary blood that can be collected for performing blood tests. In this way, blood sampling can be performed without the use of a lancet. However, any injectate that mixes with the collected blood dilutes the sample and may significantly impact subsequent analyses. By adding the fluorescent marker indocyanine green to the injected liquid, the fraction of injectate mixed into the collected blood can be measured. The incorporation of colorimetry allows our system to also correct for the impact of hematocrit on fluorescence. The results from this system show that it can determine the dilution of blood that has been diluted by up to 10 %, the upper limit of dilution typically observed in lancet-free blood sampling via jet injection.Clinical Relevance- Blood samples can be collected by jet injection without significant dilution, avoiding the need for lancing.

Humoral immunogenicity of a Coronavirus Disease 2019 (COVID-19) DNA vaccine in rhesus macaques (Macaca mulatta) delivered using needle-free jet injection.

A SARS-CoV-2 DNA vaccine targeting the spike protein and delivered by jet injection, nCOV-S(JET), previously shown to protect wild-type and immunosuppressed Syrian hamsters (Mesocricetus auratus), was evaluated via two needle-free delivery methods in rhesus macaques (Macaca mulatta). The methods included intramuscular delivery of 2 mg per vaccination with the PharmaJet Stratis device and intradermal delivery of 0.4 mg per vaccination with the PharmaJet Tropis device. We hypothesized that the nCOV-S(JET) vaccine would mount detectable neutralizing antibody responses when delivered by needle-free jet injection by either the intradermal or intramuscular route. When delivered intramuscularly, the vaccines elicited neutralizing and variant (Beta, Gamma, and Delta) cross-neutralizing antibodies against SARS-CoV-2 in all six animals after three vaccinations. The neutralizing response to Omicron was lower with only 4 of 6 animals responding. When delivered at a lower dose by the intradermal route, strong neutralizing antibody responses were only detected in two of six animals. This study confirms that a vaccine previously shown to protect in a hamster model can elicit neutralizing and cross-neutralizing antibodies against SARS-CoV-2 in nonhuman primates. We posit that nCOV-S(JET) has the potential for use as booster vaccine in heterologous vaccination strategies against COVID-19.

A Promising Needle-Free Pyro-Drive Jet Injector for Augmentation of Immunity by Intradermal Injection as a Physical Adjuvant.

Current worldwide mRNA vaccination against SARS-CoV-2 by intramuscular injection using a needled syringe has greatly protected numerous people from COVID-19. An intramuscular injection is generally well tolerated, safer and easier to perform on a large scale, whereas the skin has the benefit of the presence of numerous immune cells, such as professional antigen-presenting dendritic cells. Therefore, intradermal injection is considered superior to intramuscular injection for the induction of protective immunity, but more proficiency is required for the injection. To improve these issues, several different types of more versatile jet injectors have been developed to deliver DNAs, proteins or drugs by high jet velocity through the skin without a needle. Among them, a new needle-free pyro-drive jet injector has a unique characteristic that utilizes gunpower as a mechanical driving force, in particular, bi-phasic pyrotechnics to provoke high jet velocity and consequently the wide dispersion of the injected DNA solution in the skin. A significant amount of evidence has revealed that it is highly effective as a vaccinating tool to induce potent protective cellular and humoral immunity against cancers and infectious diseases. This is presumably explained by the fact that shear stress generated by the high jet velocity facilitates the uptake of DNA in the cells and, consequently, its protein expression. The shear stress also possibly elicits danger signals which, together with the plasmid DNA, subsequently induces the activation of innate immunity including dendritic cell maturation, leading to the establishment of adaptive immunity. This review summarizes the recent advances in needle-free jet injectors to augment the cellular and humoral immunity by intradermal injection and the possible mechanism of action.

Evaluation of the Effectiveness of Topical Anaesthetic Gel and Needle Free Jet Anaesthesia in Root Planing: A Cross-sectional Study

Introduction: Although traditional local anaesthetic technique by injection is considered as gold standard for dental procedure, the resultant pain and anxiety caused by the needle prick makes the patient less compliant for further treatment. Many alternatives have been developed by the researchers in the last two decades. Jet anaesthesia and the topical gel are the commonly used alternatives to anaesthetise the local area. Aim: To evaluate and compare the effectiveness of topical anaesthetic gel (MucopainR gel) and jet anaesthesia (Sure ShotR needle free jet injection) during root planing. Materials and Methods: After taking consent, 20 patients who required root planning in the maxillary quadrant bilaterally were recruited for this study. A split mouth study was planned where one quadrant was anaesthetised with benzocaine 20% (MucopainR) gel, whereas sure shotR jet anaesthesia was used on the adjacent quadrant. The side and order of placement of topical gel and jet anaesthesia were randomised. The same operator delivered anaesthesia on both the sides. The root planning was carried out by another operator at two sittings and pain was assessed immediately using Visual Analogue Scale (VAS), Numerical Rating Scale (NRS) and Verbal Response Scale Statistical . Results: The mean NRS score of the jet injection group was 1.50±1.54 and that for the gel group was 3.15±2.16. Also, the mean VAS score of the jet injection group was 1.50±1.54 and that for the gel was 3.15±2.16. The difference between two groups were statistically significantly (p-value=0.008). Conclusion: Jet anaesthesia was significantly superior to gel in providing anaesthesia during root planing.

Induction of potent antitumor immunity by intradermal DNA injection using a novel needle-free pyro-drive jet injector.

The current success of mRNA vaccines against COVID-19 has highlighted the effectiveness of mRNA and DNA vaccinations. Recently, we demonstrated that a novel needle-free pyro-drive jet injector (PJI) effectively delivers plasmid DNA into the skin, resulting in protein expression higher than that achieved with a needle syringe. Here, we used ovalbumin (OVA) as a model antigen to investigate the potential of the PJI for vaccination against cancers. Intradermal injection of OVA-expression plasmid DNA into mice using the PJI, but not a needle syringe, rapidly and greatly augmented OVA-specific CD8+ T-cell expansion in lymph node cells. Increased mRNA expression of both interferon-γ and interleukin-4 and an enhanced proliferative response of OVA-specific CD8+ T cells, with fewer CD4+ T cells, were also observed. OVA-specific in vivo killing of the target cells and OVA-specific antibody production of both the IgG2a and IgG1 antibody subclasses were greatly augmented. Intradermal injection of OVA-expression plasmid DNA using the PJI showed stronger prophylactic and therapeutic effects against the progression of transplantable OVA-expressing E.G7-OVA tumor cells. Even compared with the most frequently used adjuvants, complete Freund's adjuvant and aluminum hydroxide with OVA protein, intradermal injection of OVA-expression plasmid DNA using the PJI showed a stronger CTL-dependent prophylactic effect. These results suggest that the novel needle-free PJI is a promising tool for DNA vaccination, inducing both a prophylactic and a therapeutic effect against cancers, because of prompt and strong generation of OVA-specific CTLs and subsequently enhanced production of both the IgG2a and IgG1 antibody subclasses.

Jet-Induced Tissue Disruption for Blood Release.

Needle-free jet injection is a drug delivery technique that uses the momentum of the fluid drug to break through the skin. This technique has recently also been applied to blood release, aiming to collect samples from capillaries in the skin without needing a lancet prick. This work provides new information about the wound geometry and tissue disruption caused by shallow jet injection with circular-shaped and slot-shaped jets. We use histological analysis to compare the disruption of tissue, including blood vessels, caused by lancet-pricking and jet injection with a circular-shaped jet and a lancet-inspired slot-shaped jet. Intradermal injection into porcine skin using a slot-shaped jet disrupted more vascular endothelium in the tissue than a circular-shaped jet and did so at a smaller penetration depth with smaller wound volume. Our results suggest that shallow jet injections may have the potential to release more capillary blood than a lancet prick. These findings demonstrate that a reversible jet injector might be used in diabetes management as a device to release and collect blood samples, in addition to being used to deliver insulin. Tissue disruption is crucial to consider when using jet injection to deliver drugs and release capillary blood.

Flow field analysis and structure optimization of high-dose multi-hole needle-free jet injector

At present, the single-hole needle-free jet injector has a small injection dose and cannot complete a high-dose liquid injection at one time. This paper proposes a high-dose multi-hole needle-free jet injector to solve this problem. The flow field of the single-hole needle-free jet injector was analyzed by ANSYS Workbench platform, it is found that when the taper angle of the micro-hole is 20° and the aspect ratio is 1.4, the needle-free jet injector can gain a higher exit velocity. According to the simulation results, an orthogonal test was designed to optimize the contraction section of the multi-hole needle-free jet injector. The optimized scheme was obtained as follows: the taper angle of 10°, the aspect ratio of 1.6, the diameter of the distribution circle of 2.6 mm, the contraction section length of 4.35 mm and the diameter of the micro-hole of 0.195 mm. And through the stress analysis of ampoule, it is verified that the optimized scheme can meet the mechanical property requirements of the material. The optimization results show that the dose can be up to 5 ml, a high dose than the traditional single-hole injector, and the injection speed is as high as 150 m/s, which can penetrate the skin without causing too much damage. The feasibility of the optimization scheme is further verified by skin injection simulation, velocity experiment and kinetic analysis.

A DNA vaccine targeting VEE virus delivered by needle-free jet-injection protects macaques against aerosol challenge

We have previously shown that DNA vaccines expressing codon optimized alphavirus envelope glycoprotein genes protect both mice and nonhuman primates from viral challenge when delivered by particle-mediated epidermal delivery (PMED) or intramuscular (IM) electroporation (EP). Another technology with fewer logistical drawbacks is disposable syringe jet injection (DSJI) devices developed by PharmaJet, Inc. These needle-free jet injection systems are spring-powered and capable of delivering vaccines either IM or into the dermis (ID). Here, we evaluated the immunogenicity of our Venezuelan equine encephalitis virus (VEEV) DNA vaccine delivered by either the IM- or ID-DSJI devices in nonhuman primates. The protective efficacy was assessed following aerosol challenge. We found that a prime and single boost by either the IM or ID route resulted in humoral and cellular immune responses that provided significant protection against disease and viremia. Although the ID route utilized one-fifth the DNA dose used in the IM route of vaccination, and the measured humoral and cellular immune responses trended lower, the level of protection was high and performed as well as the IM route for several clinical endpoints.