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Introduction: Striae distensae (SD), or stretch marks, result from rapid stretching of the skin due to various factors. Conventional treatments often yield unsatisfactory results, leading to the exploration of alternative methods. Laser-induced microjet technology offers a promising approach for drug delivery to target areas. This study investigates the efficacy of using a microjet injector with poly-d,l-lactic acid for treating SD., Methods: Four female participants with SD were treated with poly-d,l-lactic acid solution using a microjet injector over five sessions. Patients were assessed based on severity scales before and after treatment. Topical anesthetics were applied to minimize discomfort. Injection techniques were optimized to reduce side effects such as bleeding and pain., Results: All patients showed significant improvement in SD appearance after 5-7 treatments. Assessment scales indicated positive outcomes both immediately after treatment and at the 32-week follow-up. Minimal side effects, primarily petechiae, were observed., Discussion: Laser-induced microjet technology offers several advantages, including rapid drug delivery and mechanotransduction effects, promoting skin regeneration. Poly-d,l-lactic acid injections demonstrated effectiveness in treating SD, particularly when delivered via microjet injectors. Patients expressed high satisfaction due to the procedure's minimal invasiveness and quick recovery., Conclusion: Utilizing a needleless microjet injector with poly-d,l-lactic acid shows promise as a treatment for SD, typically requiring 5-7 sessions for optimal results. Mild petechiae may occur as a common side effect. This approach offers an effective and minimally invasive alternative for addressing this common cosmetic concern., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Poor glycemic management persists among people practicing insulin therapy in relation to type 1 and 2 diabetes despite a clear relationship with negative health outcomes. Skin penetration by jet injection has recently been shown as a viable method for inducing blood release from fingertips. This study examines the use of vacuum to enhance the volume of blood released and quantifies any dilution of the collected blood., Methods: A single-blind crossover study involving 15 participants, each receiving four different interventions, was conducted wherein each participant served as their own control. Each participant experienced fingertip lancing and fingertip jet injection, both with and without applied vacuum. Participants were divided into three equal groups to explore different vacuum pressures., Results: This study found that glucose concentration in blood collected under vacuum following jet injection and lancing were equivalent. We found that applying a 40 kPa vacuum following jet injection produced a 35-fold increase in the collected volume. We determined the limited extent to which the injectate dilutes blood collected following jet injection. The mean dilution of blood collected by jet injection was 5.5%. We show that jet injection is as acceptable to patients as lancing, while being equally suited for conducting glucose measurements., Conclusions: Vacuum significantly enhances the volume of capillary blood released from the fingertip without any difference in pain. The blood collected by jet injection with vacuum is equivalent to that from lancing for glucose measurement purposes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.T. has a minority interest in medical device company Portal Instruments, Inc.

Needle-free jet injectors have been proposed as an alternative to injections with hypodermic needles. Currently, a handful of commercial needle-free jet injectors already exist. However, these injectors are designed for specific injections, typically limited to large injection volumes into the deeper layers beneath the skin. There is growing evidence of advantages when delivering small volumes into the superficial skin layers, namely the epidermis and dermis. Injections such as vaccines and insulin would benefit from delivery into these superficial layers. Furthermore, the same technology for small volume needle-free injections can serve (medical) tattooing as well as other personalized medicine treatments. The research dedicated to needle-free jet injectors actuated by laser energy has increased in the last decade. In this case, the absorption of the optical energy by the liquid results in an explosively growing bubble. This bubble displaces the rest of the liquid, resulting in a fast microfluidic jet which can penetrate the skin. This technique allows for precise control over volumes (pL to µL) and penetration depths (µm to mm). Furthermore, these injections can be tuned without changing the device, by varying parameters such as laser power, beam diameter and filling level of the liquid container. Despite the published research on the working principles and capabilities of individual laser-actuated jet injectors, a thorough overview encompassing all of them is lacking. In this perspective, we will discuss the current status of laser-based jet injectors and contrast their advantages and limitations, as well as their potential and challenges., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

X-ray free-electron lasers (XFELs) enable obtaining novel insights in structural biology. The recently available MHz repetition rate XFELs allow full data sets to be collected in shorter time and can also decrease sample consumption. However, the microsecond spacing of MHz XFEL pulses raises new challenges, including possible sample damage induced by shock waves that are launched by preceding pulses in the sample-carrying jet. We explored this matter with an X-ray-pump/X-ray-probe experiment employing haemoglobin microcrystals transported via a liquid jet into the XFEL beam. Diffraction data were collected using a shock-wave-free single-pulse scheme as well as the dual-pulse pump-probe scheme. The latter, relative to the former, reveals significant degradation of crystal hit rate, diffraction resolution and data quality. Crystal structures extracted from the two data sets also differ. Since our pump-probe attributes were chosen to emulate EuXFEL operation at its 4.5 MHz maximum pulse rate, this prompts concern about such data collection.

Background and Objectives: Many cutaneous drug-delivery techniques rely on passive diffusion to deliver topical compounds to the skin. When attempting to deliver drugs to thicker lesions, such as skin tumors, modalities that do not rely on diffusion may serve as a better drug-delivery method. In this histological study, we aim to investigate the cutaneous delivery patterns of an electronic pneumatic needle-free injection device., Study Design/materials and Methods: Needle-free-injection was investigated in 24 ex vivo porcine skin samples and one basal cell carcinoma (BCC) tissue sample. A needle-free injection device with a nozzle size of 200 μm delivered 80 μl compound ink (0.1 cc black ink: 5.0 cc saline) at low (30%/3.1 bar; n = 6 porcine skin; n = 1 BCC tissue), medium (50%/3.9 bar; n = 6 porcine skin), high (65%/4.6 bar; n = 6 porcine skin), and stacked (30 + 50%/3.1 + 3.9 bar; n = 6 porcine skin) pressures. Depth, width, and depth of maximum width of ink deposition were evaluated on histological slides., Results: Depositions with small ink-lined vacuoles were seen intra-dermally in all samples, including the BCC tissue. Deposition depth was similar at low and medium pressures (924 vs. 994 μm; P = 0.873) but increased significantly with high pressure (1,564 μm; P = 0.010). When injections were stacked (3.1 + 3.9 bar), the depth remained similar to that of a single injection (931 μm; P = 1.000). The width of the deposition stayed comparable for low, medium, and high pressures when a single needle-free injection was performed (30% = 2,394 μm; 50% = 2,226 μm; and 65% = 2,757 μm; P = 0.09), but increased significantly with stacking (2,979 μm; P = 0.037). The depth of maximal width was superficially located in the papillary dermis at low and medium pressures (321 and 305 μm; P = 0.748) but shifted to the deeper reticular dermis with high pressure (950 μm; P = 0.004) and with stacking (734 μm; P = 0.004)., Conclusions: In conclusion, with an electronically controlled, pneumatic needle-free injector, depth and width of a cutaneous deposition can be influenced by pressure and stacking, respectively. The pneumatic needle-free injection can potentially serve as a viable drug-delivery technique for cutaneous pathologies where dermal deposition is essential. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Objective: Jet injectors use a high-pressure liquid jet to pierce the skin and deliver drug into underlying tissues. This jet is formed through a short, narrow orifice; the geometry of the orifice and the properties of the fluid affect the nature of the flow. We aimed to discover information about the turbulent and viscous processes that contribute to pressure loss and flow patterns during jet injection., Methods: We used computational fluid dynamics methods and experimental observation to investigate the effects of nozzle geometry, fluid viscosity, and viscous heating on jet production. We experimentally verified the temperature change of the jet during ejection, using an infrared camera., Results: Our models accurately predict the average jet speed produced for two example nozzle geometries over two orders of magnitude of viscosity. The models reveal the previously unreported importance of viscous heating in the formation of the jet. Temperatures >65 °C were predicted at the edge of the flow as a result of viscous heating. These caused a significant local reduction in viscosity and effectively allowed the fluid to lubricate itself. Our experiments confirmed changes in mean jet temperature of up to 2.5 °C, which are similar to those predicted by our model (∼2.8 °C)., Conclusion: These results reveal the importance of the viscous heating properties of a fluid in the formation of high-speed jets for drug delivery., Significance: This property is crucial to consider when formulating new drugs for needle-free jet injection.

Needle-free drug delivery is highly sought after for reduction in sharps waste, prevention of needle-stick injuries, and potential for improved drug dispersion and uptake. Whilst there is a wealth of literature on the array of different delivery methods, jet injection is proposed as the sole candidate for delivery of viscous fluids, which is especially relevant with the advent of DNA-based vaccines. The focus of this study was therefore to assess the role of viscosity and jet configuration (i.e. stand-off relative to the skin) upon injection efficiency for a fixed spring-loaded system (Bioject ID Pen). We performed this assessment in the context of mouse cadavers and found that the dominant factor in determining success rates was the time from euthanasia, which was taken as a proxy for the stiffness of the underlying tissue. For overall injection efficiency, ANOVA tests indicated that stiffness was highly significant (P <  < 0.001), stand-off was moderately significant (P < 0.1), and viscosity was insignificant. In contrast, both viscosity and standoff were found to be significant (P < 0.01) when evaluating the percentage delivered intradermally. Using high-resolution micro-computed tomography (μ-CT), we also determined the depth and overall dispersion pattern immediately after injection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Various jet injectors have been developed and used for the effective and efficient administration of drugs. Jet injections overcome the limitations of other drug delivery methods, such as ablation, iontophoresis, electroporation, sonophoresis, and microneedles, because jet injection is not limited by the diffusion rates of different drugs. However, controlling the jet pressure during drug delivery is difficult with most conventional jet injectors. Efficacy evaluation of such devices on laboratory animals is strongly required before initiating human clinical trials, but minimal research has been performed for the device developments. Therefore, we developed jet injector devices based on pyrotechnics using 2 types of explosives with different burning rates; we call these pyro-drive jet injectors. The liquid jet pressure profile suggests that the penetration depth and injection volume for soft materials and skin tissue are controllable. Here, we propose the pyro-drive jet injectors as another candidate well-controlled jet injector for laboratory animals in drug discovery testing as well as human clinical use., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

We present a new mechanism for achieving needle free jet injection that significantly reduces the power required to perform a given injection. Our 'compound ampoule' produces two phases of jet speed under a constant force input by changing the effective piston area part-way through the injection. In this paper we define the benefits associated with a compound ampoule, relative to those of the conventional single piston design, by developing expressions for the power and energy required to perform an injection. We demonstrate that a compound ampoule can reduce the maximum input power required to perform a jet injection to less than one fifth of that previously required, enabling motors of less than half the mass to perform the same injection. We then detail the development of a prototype compound ampoule injector. Results from testing of this prototype demonstrate the function of a compound ampoule and verify the expected reduction in the required power and energy. Injections into post mortem porcine tissue confirm that our compound ampoule prototype can achieve the delivery of 1 mL of liquid into post-mortem tissue at least as effectively as a conventional ampoule. This approach will advance progress toward light-weight and power-efficient needle-free jet injectors for transdermal drug delivery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Jet injection presents a promising alternative to needle and syringe injection for transdermal drug delivery. The controllability of recently-developed jet injection devices now allows jet speed to be modulated during delivery, and has enabled efficient and accurate delivery of volumes up to 0.3 mL. However, recent attempts to inject larger volumes of up to 1 mL using the same methods have highlighted the different requirements for successful delivery at these larger volumes. This study aims to establish the jet speed requirements for delivery of 1 mL of liquid using a controllable, voice coil driven injection device. Additionally, the effectiveness of a two-phase jet speed profile is explored (where jet speed is deliberately decreased toward the end of the injection) and compared to the constant jet speed case. A controllable jet injection device was developed to deliver volumes of 1 mL of liquid at jet speeds >140 m/s. This device was used to deliver a series of injections into post-mortem porcine tissue in single and two-phase jet speed profiles. Single-phase injections were performed over the range 80 m/s to 140 m/s. Consistent delivery success (>80% of the liquid delivered) was observed at a jet speed of 130 m/s or greater. Consistent penetration into the muscle layer coincided with delivery success. Two-phase injections of 1 mL were performed with a first phase volume of 0.15 mL, delivered at 140 m/s, while the injection of the remainder of fluid was delivered at a second phase speed that was varied over the range 60 m/s to 120 m/s. Ten two-phase injections were performed with a second phase speed of 100 m/s producing a mean delivery volume of 0.8 mL ± 0.2 mL, while the single-phase injections at 100 m/s achieved a mean delivery volume of 0.4 mL ± 0.3 mL. These results demonstrate that a reduced jet speed can be used in the later stages of a 1 mL injection to achieve delivery success at a reduced energy cost. We found that a jet speed approaching 100 m/s was required following initial penetration to successfully deliver 1 mL, whereas speeds as low as 50 m/s have been used for volumes of <0.3 mL. These findings provide valuable insight into the effect of injection volume and speed on delivery success; this information is particularly useful for devices that have the ability to vary jet speed during drug delivery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: We conducted a randomized, non-inferiority, clinical study of MMR vaccine by a disposable-syringe jet injector (DSJI) in toddlers in India in comparison with the conventional administration., Methods: MMR vaccine was administered subcutaneously by DSJI or needle-syringe (N-S) to toddlers (15-18 months) who had received a measles vaccine at 9 months. Seropositivity to measles, mumps, and rubella serum IgG antibodies was assessed 35 days after vaccination. Non-inferiority was concluded if the upper limit of the 95% CI for the difference in the percent of seropositive between groups was less than 10%. Solicited reactions were collected for 14 days after vaccination by using structured diaries., Results: In each study group, 170 subjects received MMR vaccine. On day 35, seropositivity for measles was 97.5% [95% CI (93.8%, 99.3%)] in the DSJI group and 98.7% [95% CI (95.5%, 99.8%)] in the N-S group; for mumps, 98.8% [95% CI (95.6%, 99.8%)] and 98.7% [95% CI (95.5%, 99.8%)]; and for rubella, 98.8% [95% CI (95.6%, 99.8%)] and 100% [95% CI (97.7%, 100.0%)]; none of the differences were significant. The day 35 post-vaccination GMTs in DSJI and N-S groups were measles: 5.48 IU/ml [95% CI (3.71, 8.11)] and 5.94 IU/ml [95% CI (3.92, 9.01)], mumps: 3.83 ISR [95% CI (3.53, 4.14)] and 3.66 ISR [95% CI (3.39, 3.95)] and rubella: 95.27 IU/ml [95% CI (70.39, 128.95)] and 107.06 IU/ml [95% CI (79.02, 145.06)]; none of the differences were significant. The DSJI group reported 173 solicited local reactions and the N-S group reported 112; most were mild grade. Of the total of 156 solicited systemic adverse events, most were mild, and incidence between the two groups was similar., Conclusions: MMR vaccination via DSJI is as immunogenic as vaccination by N-S. Safety profile of DSJI method is similar to N-S except for injection site reactions which are more with DSJI and are well-tolerated. Registration US National Institutes of Health clinical trials identifier - NCT02253407. Clinical trial registry of India identifier - CTRI/2013/05/003702., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Intradermal immunization of mice against hepatitis B surface antigen (HBsAg) using a novel real-time controlled jet injector was assessed by comparison with intradermal and subcutaneous injection of antigen using a 27G needle and syringe. Three doses of aluminium-absorbed HBsAg were delivered at 0, 14, and 28days. Antibodies to HBsAg were detected only in mice injected with antigen with antibody levels increasing with secondary injections. Mice vaccinated by intradermal injection using the jet injector or subcutaneous needle injection exhibited comparable immune responses at day 47. Differences in titer observed between intradermal jet injected and needle injected animals reflect differences in the volume of antigen delivered. With the exception of minor bleeding at the injection site in a few animals injected either by jet injection or needle, no adverse events were observed in any of the mice used in the study., (Copyright © 2017. Published by Elsevier B.V.)

Background: Needle-free, transcutaneous pneumatic injection systems can be used to deliver therapeutic solutions to targeted layers of skin in a minimally invasive manner., Methods: To evaluate jet infiltration patterns and tissue reactions, 5% isotonic and 20% hypertonic glucose solutions were pneumatically injected into in vivo micropig skin. Gelatin TM phantom was additionally prepared to analyze penetration and dispersion patterns for different experimental settings., Results: As immediate tissue reactions in the in vivo micropig skin, distinct pneumatic injection injury zones (PIIZs) in the dermis, extending from the papillary dermis deep into the dermo-subcutaneous junction, were generated with the 5% and 20% glucose solutions and with pneumatic pressures of 4.64 and 5.7 bars, respectively. PIIZs markedly decreased in appearance at 1 day after treatment, accompanied by inflammatory cell infiltration, and disappeared at 7 days post-treatment with increased collagen and elastin production. In TM phantom study, the PIIZs created by 20% glucose mainly comprised a single, homogenous, round to oval zone, whereas those created by 5% glucose were irregular and multi-lobular., Conclusion: The present study suggests that transcutaneous pneumatic injection therapy may exert mechanical stimulatory effects, immediate tissue shrinkage via hypertonic solutions, and late tissue regeneration effects during wound healing., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study is conducted to investigate efficacy of an insulin jet injector and an insulin pen in treatment of type 2 diabetic patients. Sixty patients with type 2 diabetes were treated with rapid-acting insulin (regular insulin) and insulin analog (insulin aspart) using the jet injector and the pen in 4 successive test cycles. Postprandial glucose and insulin concentrations in blood were measured over time. Areas under curves of glucose and the insulin were calculated, and efficacy of 2 injection methods in treatment of the diabetes was compared. Regular insulin and insulin aspart administration by the jet injector showed significant decreases in plasma glucose levels as compared to the pen injection (P < 0.05). Postprandial plasma glucose excursions at the time points of 0.5 to 3 hours were obviously lower in the jet-treated patients than the pen-treated ones (P < 0.05). Postprandial plasma insulin levels were markedly higher in the jet-treated patients than the pen-treated ones (P < 0.05). Area under the glucose curve in the pen-treated patients was significantly increased as compared to the jet-treated ones (P < 0.01). Efficacy of the insulin jet injector in treatment of type 2 diabetic patients is obviously superior to the insulin pen in regulating plasma glucose and insulin levels., Competing Interests: The authors have no funding and conflicts of interest to disclose.

This article presents a miniature shock wave driven micro-jet generator to deliver liquid drugs into human skin, to a controlled depth, with minimal invasion. The device can release the vaccine/drug to the depth of dermal blood vessels, without breaching much of the microcirculation system of dermis. The drug delivery technique is needle-free, which can reduce pain, trauma, and contamination besides minimal dosage and systemic exposure. The device can also be used to deliver liquid or colloidal drugs into soft tissues in human. The mechanical analyses of the device were carried out by analyzing the strength of the impulse of the shock wave, measuring the velocity of the generated jet and capturing the pressure exerted by the jet on the target. The penetrating ability of the jet was investigated by delivering it into sample of human skin and gelatin slabs. Theoretical analyses were carried out on the physics of the delivery and the predicted results had a close agreement with the experimental observations. The development can offer an important cost-effective solution to needle-free health care worldwide. Biotechnol. Bioeng. 2016;113: 2507-2512. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

We present a needle-free jet injection device controllably actuated by a voice coil and capable of injecting up to 1.3 mL. This device is used to perform jet injections of ~900 μL into porcine tissue. This is the first time that delivery of such a large volume has been reported using an electronically controllable device. The controllability of this device is demonstrated with a series of ejections where the desired volume is ejected to within 1 % during an injection at a predetermined jet velocity.

Drugs can be delivered transdermally using jet injectors, which can be an advantageous route compared to oral administration. However, these devices inject large volumes deep into the skin or tissues underneath the skin often causing bruising and pain. This may be prevented by injecting smaller volumes at lower depth in a repetitive way using a microjet injection device. Such a device could be used to apply drugs in a controllable and sustainable manner. However, the efficacy of microjet injection has been rarely examined. In this study, the penetration and delivery capacity was examined of a repetitive microjet injection device. Various experiments were performed on epidermal and full-thickness ex vivo human as well as ex vivo porcine skin samples. Results revealed that microjets with a velocity exceeding 90m/s penetrated an epidermal skin sample with a delivery efficiency of approximately 96%. In full-thickness human skin, the delivery efficiency drastically decreased to a value of approximately 12%. Experiments on full-thickness skin revealed that the microjets penetrated to a depth corresponding to the transition between the papillary and reticular dermis. This depth did not further increase with increasing number of microjets. In vivo studies on rats indicated that intact insulin was absorbed into the systemic circulation. Hence, the microjet injection device was able to deliver medication into the skin, although the drug delivery efficiency should be increased., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Endoscopic treatment of superficial gastrointestinal tumors is routinely performed, however the advantages and shortcomings of submucosal pressure-jet dissection is still debated., Objective: - Aiming to compare this technique with conventional submucosal dissection, a study was designed in pigs., Methods: - Areas of the antral mucosa of the stomach with a diameter of 2 cm2 (6 per animal) were marked, and resected by means of the hybrid-knife (experimental technique), and Flush-knife or IT-knife (controls). An ERBE ICC 300 electrosurgical unit was adopted. End-points were procedural time, complications, and quality of the resected specimen., Results: - A total of 27 interventions were conducted in five animals. Time spent with the two options was quite short, and similar: 9.5±3.1 vs 8.0±3.0 minutes (P=0.21). Complications didn't differ (three per group, not significant), and removed specimen looked adequate in both circumstances., Conclusion: - The hybrid-knife technique is an acceptable alternative to submucosal dissection, showing no difference compared to the standard technique taking into consideration the procedure, the presence of complications and the quality of the resected specimen.

Pre-filled syringes (PFS) and auto-injection devices with cartridges are increasingly used for parenteral administration. To assure functionality, silicone oil is applied to the inner surface of the glass barrel. Silicone oil migration into the product can be minimized by applying a thin but sufficient layer of silicone oil emulsion followed by thermal bake-on versus spraying-on silicone oil. Silicone layers thicker than 100nm resulting from regular spray-on siliconization can be characterized using interferometric profilometers. However, the analysis of thin silicone layers generated by bake-on siliconization is more challenging. In this paper, we have evaluated Fourier transform infrared (FTIR) spectroscopy after solvent extraction and a new 3D-Laser Scanning Microscopy (3D-LSM) to overcome this challenge. A multi-step solvent extraction and subsequent FTIR spectroscopy enabled to quantify baked-on silicone levels as low as 21-325μg per 5mL cartridge. 3D-LSM was successfully established to visualize and measure baked-on silicone layers as thin as 10nm. 3D-LSM was additionally used to analyze the silicone oil distribution within cartridges at such low levels. Both methods provided new, highly valuable insights to characterize the siliconization after processing, in order to achieve functionality., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We present a novel method of quickly acquiring dermal interstitial fluid (ISF) samples using a Lorentz-force actuated needle-free jet injector. The feasibility of the method is first demonstrated on post-mortem porcine tissue. The jet injector is used to first inject a small volume of physiological saline to breach the skin, and the back-drivability of the actuator is utilized to create negative pressure in the ampoule and collect ISF. The effect of the injection and extraction parameters on sample dilution and extracted volumes is investigated. A simple finite element model is developed to demonstrate why this acquisition method results in faster extractions than conventional sampling methods. Using this method, we are able to collect a sample that contains up to 3.5% ISF in 3.1s from post-mortem skin. The trends revealed from experimentation on post-mortem skin are then used to identify the parameters for a live animal study. The feasibility of the acquisition process is successfully demonstrated using live rats; the process is revealed to extract samples that have been diluted by a factor of 111-125., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Conventional injection is still the leading method to deliver macromolecular therapeutics. Needle injection is considered a low compliance administration strategy, principally due to pain and needle phobia. This has fostered the research on the development of alternative strategies to circumvent the skin barrier. Among needle-free drug delivery methods, jet injection is an old strategy with great potential not yet completely disclosed. Here, the design, engineering and dynamic behavior of a novel spring-powered micronozzle needle-free injector is presented. Fluid mechanics was first studied in air to calculate jet force and speed as well as injection duration in different conditions. Polyacrylamide gel was used to simulate a soft tissue and to investigate the jet evolution over time of different injected doses. Finally, ex vivo characterization was carried out on pig skin. Results evidenced a direct dependence of the force, velocity, and duration with the injection volume. The model material allowed individuating the different steps of jet penetration and to attempt a mechanistic explanation. A different behavior has been recorded in the skin with interesting findings for subcutaneous and/or dermal delivery. Peculiar features with respect to existing jet injectors confers to this device good potentiality for a future clinical application., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This paper describes the effect of drug viscosity on the performance of gas powered liquid jet injectors. The analysis is accomplished utilizing a Computational Fluid Dynamics (CFD) model that obtains the stagnation pressure at the nozzle outlet. The technique is based on previous work used to predict gas power driven injector piston velocity with time. The results depict the variation in average and peak injector stagnation pressure for three different driven pressures; driving injections which vary from 0.2 cP to 87 cP in viscosity. Furthermore, a numerical representation of jet shape is also obtained to verify the effect of viscosity on jet geometry. These results demonstrate that increasing viscosity by 10 times that of water produces only a slight decrease in injector stagnation pressure and produces jets with greater confinement, which will display better characteristics for puncturing the skin.

We present a new design for a needle-free injector ampoule, using two concentric pistons to pressurize the fluid during the injection. The smaller, inner piston is used to provide an initial high-velocity piercing jet; it then engages the outer piston to deliver the remaining drug via a low-velocity jet. The goal of this design is to enable needle-free delivery of relatively large volumes to controlled depths in tissue, a task impractical with conventional ampoules and actuators. We demonstrate this concept by constructing a 1.2mL ampoule, measuring the jet velocity it produces in free air, and performing a set of injections into post-mortem porcine tissue. The ampoule smoothly produces the two desired phases of an injection, with a smooth transition of jet velocity as the two pistons engage. The injection is able to penetrate porcine skin to a controlled depth and deliver fluid to the subcutaneous and/or intramuscular layers, though further investigation is required to ensure that all of the fluid delivered can be retained at the desired depth.

The effects of the dispersion pattern of a needle-free jet injector are explored. The shape of the jets were compared using a high-speed video camera and jet injections of collimated and dispersed fluid jets with a Lorentz-force actuated jet injector were made into acrylamide gel and post-mortem porcine tissue. A custom-built high-speed X-ray imaging system was used in order to observe the dynamics of the dispersion mechanism for each injection in real time. We show that a collimated jet stream results in greater tissue penetration than a dispersed jet stream.

A nonlinear, sliding mode adaptive controller was created for a needle-free jet injection system. The controller was based on a simplified lumped-sum parameter model of the jet-injection mechanics. The adaptive control scheme was compared to a currently-used Feed-forward+PID controller in both ejection of water into air, and injection of dye into ex-vivo porcine tissue. The adaptive controller was more successful in trajectory tracking and was more robust to the biological variations caused by a tissue load.

Monoclonal antibodies (mAbs) represent a major group of biotherapeutics. The high concentration and volume of drug administered together with a shift to administration via the subcutaneous route have generated interest in alternative delivery technologies. The feasibility of using a novel, highly controllable jet injection technology to deliver a mAb is presented. The effect of delivery parameters on protein structure were evaluated and compared with delivery using a conventional needle and syringe. Injection of mAb into a rat model showed that jet injection using the device resulted in more rapid absorption and longer duration of exposure.

Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection (PNI) device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors (gas pressure, cylinder volume, and nozzle distance) were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs.

We present a scaling model for electrically-actuated needle free jet injectors, establishing the relationship between injection volume and motor size. Using an analytical electromagnetic model for the motor, we derive an optimal motor design, and show that this design is approximately scale-invariant. To illustrate the utility of this model, we then describe the design of a motor for use with 300 μL disposable injection ampoules with a mass of just 300 g, including a light-weight support structure. Experimental verification of the motor performance shows close agreement to model predictions, with a peak force of 1000 N/kg and a 150 m/s water jet delivered.

To improve the safety of the use of a power injector for pediatric contrast CT, we newly developed a saline test injection mode for a power injector and investigated its usefulness. We used an injection route and investigated the relationship of the injection pressure to the injection rate of saline and the contrast medium. From this relationship, we investigated it was possible to estimate the change of pressure injection of contrast medium from the pressure change of saline injection. The correlation between the saline test injection pressure and the contrast medium injection pressure was investigated in 64 clinical cases. The detection rate of side effects from the saline test injection was investigated in 473 patients. Regarding the correlation between the injection rate and pressure for both saline and contrast, the pressure rose as the rate increased. The contrast medium injection pressure could be estimated from the correlation observed with saline. The clinical data were obtained had a relationship similar to that with phantom data. The detection rate of side effects from the saline test injection was 4.4% in the clinical cases. In these cases, examinations were completed by re-establishing an injection route or administering hypnotics. Our results suggest that contrast medium pressure can be estimated from a saline test injection, thus aiding in prediction of the risk of injection abnormality. Reactions to injections could be observed in the present study, facilitating the prevention of examination failure. Countermeasures can be taken against the cause of the reaction, and the examination can be performed after confirming the absence of a reaction to injection. Therefore, a saline test injection may be useful in pediatric contrast CT.

An experimental study was performed using a custom-built air-powered needle-free injector to investigate the various injector parameters governing the dynamics of jet injection. A parametric study using five different nozzle sizes at driver pressure ranging from 4 to 8 bar was carried out. The fluid stagnation pressure of the liquid jet was determined using a Honeywell force sensor. Performance plots as a function of various parameters were constructed. It was determined that as the driver pressure increased both the peak and average stagnation pressure increased almost linearly within the operating range considered. Varying the injection nozzle diameter, whilst keeping the driver pressure constant did not have any significant impact on the peak or average stagnation pressure. The chamber length was also varied and no significant influence was found on peak or average stagnation pressure.

The feasibility of a new method of quickly acquiring interstitial fluid (ISF) samples using a Lorentz-force actuated needle-free jet injector is demonstrated on ex vivo porcine tissue. The jet injector is used to first inject a small volume of physiological saline to breach the skin, and the back-drivability of the actuator is utilized to create a vacuum in the ampoule and collect ISF. Injection and extraction parameters are tested and optimized for minimal acquired sample dilution and extracted volume consistency. Using this method, we are able to collect a sample that contains up to 3.5% ISF in 3.1 s.

The microjet injector system accelerates drugs and delivers them without a needle, which is shown to overcome the weaknesses of existing jet injectors. A significant increase in the delivered dose of drugs is reported with multiple pulses of laser beam at lower laser energy than was previously used in a Nd:YAG system. The new injection scheme uses the beam wavelength best absorbable by water at a longer pulse mode for elongated microjet penetration into a skin target. A 2.9 μm Er:YAG laser at 250 μs pulse duration is used for fluorescent staining of guinea pig skin and for injection controllability study. Hydrodynamic theory confirms the nozzle exit jet velocity obtained by the present microjet system.

Objective: FT (FlexTouch*) is a new disposable insulin injection pen device for use in insulin-treated patients with diabetes mellitus. The aim of this study was to evaluate patient perception of FT versus IL (InnoLet†) with respect to the ease of use and patient preference in a mixed patient cohort with different kinds and degrees of visual or dexterity impairments., Methods: Ninety patients were included into this investigation (54 male/36 female, age [mean ± SD]: 62 ± 8 yrs, disease duration: 18 ± 11 yrs, HbA1c: 7.2 ± 1.0%). After assessment of visual acuity and dexterity skills (by Jebsen-Taylor Hand Function Test), the patients were introduced to the two pen devices in random order, and were asked to perform mock injections with 10 IU, 30 IU and 50 IU doses before completing a 41 item standardized device assessment questionnaire. The questions asked were covering five topics of pen use (confidence in delivering a correct dose, dose setting, performance of the injection, general handling, and others) and could be answered with a rank scale from '1 = very easy' to '5 = very difficult'., Results: FT was ranked superior to IL with respect to the injection procedure (FT: 1.2 ± 0.1 vs. IL: 2.1 ± 0.4, p < 0.001) and general handling (1.3 ± 0.2 vs. 2.3 ± 0.7, p < 0.001), and numerically better with respect to confidence in correct dosing (1.4 ± 0.2 vs. 2.1 ± 0.9, n.s.). The two devices were ranked equally for ease of dose setting (1.6 ± 0.3 vs. 1.7 ± 0.4, n.s.). When ranked individually, FT use was recommended by 92.2% of the patients (IL: 30.0%)., Key Limitations: Patients of this investigation were from one local area (San Jose, CA, USA) only. The subgroups may be considered small for the performed analysis., Conclusions: In summary, FT was perceived to be easier to use than IL in this investigation.

Objective: The shortest pen needle (PN) for subcutaneous insulin therapy is 4 mm. Clinicians may hesitate to use it in obese patients. We report a post hoc analysis of a previously published study of the 4 mm × 32 G PN, evaluating responses in obese (≥30 kg/m(2)) and non-obese (<30 kg/m(2))., Methods: Subjects (BMI 20 to 49 kg/m(2), 52% obese) with diabetes used 4 mm × 32 G PNs and either 5 mm or 8 mm PNs (both 31 G) in two, 3-week treatment periods in a randomized noninferiority cross-over trial. Percentage absolute change in fructosamine (%│Δ Fru│) was the primary endpoint. Equivalent glycemic control was defined as %│Δ Fru│ within 20% (including 95% CI). The impact of obesity on change in fructosamine, pain and reported insulin leakage from the skin is described., Clinical Trial Registration: Clinicaltrials.gov - identifier: NCT00928057., Limitations: This report is a post hoc analysis of two BMI subgroups resulting in smaller sample sizes., Results: Of 168 who completed the study, 163 were included in the fructosamine analyses - 83 and 80 in the 4/5 mm and 4/8 mm groups, respectively. For the 4/5 mm group, mean BMI ± SD in non-obese and obese groups were 25.9 ± 2.3 and 35.0 ± 4.9 kg/m(2), respectively; 4/8 mm group 25.2 ± 2.6 and 35.6 ± 4.2 kg/m(2). BMI group was not significant for %│Δ Fru│ for either 4/5 mm or 4/8 mm. Between BMI groups, the difference of the means in %│Δ Fru│ was 0.4% (4/5 mm) and 0.3% (4/8 mm). The 4 mm PN was significantly less painful in all subject groups, except non-obese in 4/5 mm. Regardless of needle size, obese subjects reported more leakage events. For both BMI groups, there were fewer total reported leakage events when using the 4 mm vs 5 mm and 8 mm needles., Conclusions: The 4 mm pen needle provided equivalent glycemic control in both obese and non-obese patients compared to 5 mm and 8 mm needles with no increase in reports of skin leakage, in this post-hoc analysis. These findings should be confirmed in a prospective randomized controlled trial.

We present a mathematical model of the dynamics of a previously developed needle-free jet injector (NFJI) that is based upon a servo-controlled Lorentz-force motor. The injector creates a fluid jet that can pierce through the skin and deliver a drug to dermal, subcutaneous and muscular tissue. We use the model to predict the jet speed achieved during an injection. The model simulates the electrical response of the motor coil, the mechanical response of the drug piston and ampoule and the friction incident upon the piston during the time course of the injection. High-speed video measurements of piston movement in response to a step input show that the model predicts piston-tip position during an injection within an RMS error of 287 µm. The corresponding jet speed is predicted to be 180 m·s(-1) with a maximum overshoot to 205 m·s(-1).

Background and Objective: To evaluate a minimally invasive injector for intravitreal and subconjunctival administration of medications., Materials and Methods: The device has a microneedle that communicates with an internal formulation chamber. A piercing depth-limiting flange restricts microneedle penetration to a depth of less than 1 mm and defines the location of the pars plana from the limbus. The jet injector creates a force of up to 1,000 psi, forcing the medication through the remaining sclera/choroid thickness. The device was tested in 28 enucleated rabbit eyes and 9 experimental and 4 control rabbit eyes to define jet pressure for subconjunctival and intravitreal injection., Results: Injection pressures of 76 to 156 psi were needed for subconjunctival injection and 974 psi for intravitreal injection. Clinical and histologic examinations did not reveal damage to intraocular structures., Conclusion: The semi-automated jet injector facilitated intravitreal/subconjunctival injection. The microneedle-assisted jet injector minimized the risk of wet injection by anchoring the microneedle in the sclera., (Copyright 2012, SLACK Incorporated.)

We present a new method for needle-free powdered drug injection via a bench-top gas-powered device. This injector provides an alternative method of vaccine delivery to address the cold chain problem--the cost and risk of transporting temperature sensitive vaccines to developing countries. The device houses interchangeable nozzle inserts to vary orifice geometries and is capable of delivering polymer beads (1-5 µm diameter) into the dermal layer of porcine tissue. Results for injection shape and injection depth versus nozzle orifice diameter demonstrate the device's controllability.

Intravitreal injection is a common treatment in ophthalmology, but it can lead to numerous complications. Needle-free jet injection has been shown to successfully deliver fluid to various layers of skin, and, by its nature, may reduce intravitreal injection complications. From injection trials into ex vivo rabbit eyes, we find that needle-free jet injection can be used for intravitreal drug delivery. A custom-designed control scheme, characterized in this study, is crucial to this delivery. The system is capable of delivering 40 µL of fluid to the posterior vitreous humor, with an injection duration less than 100 ms and scleral entry site less than 350 µm in diameter.

Needle-free liquid jet injectors have been developed for the delivery of several drugs including insulin and growth hormone. Here, we assess the ability of liquid jet injectors to deliver polymeric nanoparticles into skin. As a first step, polystyrene particles of several sizes and two shapes were injected into skin using a jet injector. The dispersion area of particles, measured in the cross section of the skin, was found to inversely relate to the particle size and directly proportional to the injection volume. Environmental scanning electron microscopy studies confirmed that particles indeed penetrate into the skin and are generally located around the injection site. Next, poly lactide co-glycolide (PLGA) particles, containing a model solute, coumarin-6, were synthesized and delivered into the skin using the jet injector. PLGA particles were effectively delivered into the skin and released coumarin-6 into the skin., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: A myriad of technologies are available for the treatment of aging skin. These, however, still lack the ability to combine immediate, short-term and long-term aesthetic results with no downtime. Furthermore, the treatment of fine wrinkles on large surfaces remains challenging, as does the treatment of delicate regions, such as the dorsal hand, neck, and chest., Objectives: The aims of this study were to evaluate the short-term as well as the long-term efficacy and safety of a new skin remodeling device that pneumatically accelerates a jet of hyaluronic acid (HA) solution under high pressure into the dermis., Methods: Thirty-four participants at three clinical sites underwent treatments with the Airgent device on the face, neck, chest, and dorsal hands for a total of 69 sites. Safety and efficacy were evaluated in short-term (1-3 months) and long-term follow-up (up to 18 months) by photography, by an independent reviewer and by participant self-evaluation. Histology was assessed before and 4 months after the third treatment., Results: A total of 69 treatment areas were evaluable at 1-3 months follow-up. Photographic analysis demonstrated improvement in skin variables at all body sites treated. Treatment of the face and neck reduced the mean Fitzpatrick-Goldman Wrinkle Classification score by 39.4 and 30.4%, respectively, representing a full wrinkle class improvement. Treatments of the chest demonstrated significant visual improvement. Treatment of the dorsal hands produced good overall improvement (OI), with good improvement of protruding veins. Overall improvement increased with increasing number of treatments. A total of 56 treatment areas were evaluable for long-term follow-up. Treatment of the face and neck reduced the mean Fitzpatrick-Goldman Wrinkle Classification score by 27.6 and 21.2%, respectively. Improvement after treatment of the face represented a full wrinkle class reduction. Treatment of the chest and dorsal hands yielded significant visual improvement. Overall, 80% of subjects were satisfied with the treatment outcome and would recommend the treatment to friends and family. Histological analysis demonstrated increased dermal collagen ΙΙΙ., Conclusions: Pneumatic injection of HA under high pressure provides a safe, well-tolerated and effective method for improving the appearance of wrinkles on the face, neck, chest, and dorsal hands. Improvement can be seen as early as 1 month and as long as 18 months after treatment., (© 2010 The International Society of Dermatology.)

A mathematical model has been presented for a high speed liquid jet penetration into soft solid by a needle-free injection system. The model consists of a cylindrical column formed by the initial jet penetration and an expansion sphere due to continuous deposition of the liquid. By solving the equations of energy conservation and volume conservation, the penetration depth and the radius of the expansion sphere can be predicted. As an example, the calculation results were presented for a typical needle-free injection system into which a silicon rubber was injected into. The calculation results were compared with the experimental results.

We evaluated a needle-free injector (NFI), which has been studied as an administration device to the subcutaneous tissue, as a device to deliver drugs into skin tissues. ShimaJet used for self-injection of insulin was selected as a spring-powered NFI in this study. Weak (NFI-w) and strong (NFI-s) injectors were evaluated. Rhodamine 6G, as a model compound, was injected onto the skin surface of hairless rats and the skin distribution and amount released from the skin of the compound were followed. A modified nozzle (able to inject at an angle of 45 degrees ) was prepared in addition to the conventional dedicated nozzle. The spring constants, nozzle shapes and penetration enhancer, 1-[2-(decylthio)ethyl] azacyclopentane-2-one (HPE-101), affected not only the skin distribution, but also the release profiles of rhodamine 6G. In addition, the release profiles of rhodamine 6G after injection using NFI-w or NFI-s obeyed diffusion-controlled or membrane-controlled kinetics, respectively. This difference was probably due to the skin site (depth) of rhodamine 6G delivered by the NFI. Furthermore, HPE-101 increased the retention time of rhodamine 6G in the epidermis. The present results suggested that an NFI can be a useful tool for enhanced drug delivery into skin., (Crown Copyright (c) 2010. Published by Elsevier B.V. All rights reserved.)

Background: Endoscopic submucosal dissection requires a high degree of endoscopic skill and specifically designed dissecting instruments., Objective: To describe the technique for endoscopic submucosal dissection when using the ERBE Hybrid Knife, which combines an ultrafine high-pressure water jet with an electrocautery needle., Design: Descriptive study (ex vivo and in vivo porcine esophagus, stomach, and colon)., Interventions: The only instrument used for the dissection was the ERBE Hybrid Knife. The high-pressure water jet was used at a pressure between 45 and 60 bar for creating submucosal fluid elevation. After this, circumferential mucosal incisions and submucosal dissection were performed with the FORCED COAG and ENDOCUT D modes of the same device. The water jet was used intermittently during the dissection process., Main Outcome Measurements: At the end of the in vivo experiments, animals were killed and the organs removed for evaluation., Results: Multiple endoscopic submucosal dissection procedures were successfully performed. It was possible to create submucosal fluid cushions rapidly. Repeated fluid injections during dissection were easily facilitated with the same device. All ex vivo gastric endoscopic submucosal dissections of 50 x 40-mm lesions were completed within 10 minutes. In the in vivo studies, the mean size of the gastric and colonic specimens was 3.7 +/- 2.1 x 2.3 +/- 1 cm, and the dissections were completed within 8 minutes. No thermal injury was observed on the serosa, and no perforations were detected., Conclusions: Endoscopic submucosal dissection can be safely and effectively achieved in a porcine model with the ERBE Hybrid Knife and should be considered a suitable device for this procedure in humans., (2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Endoscopic resection of colorectal nonpolypoid lesions requires adequate submucosal lifting of the lesion., Objective: To evaluate a self-assembled hydro-jet system for tissue elevation to improve endoscopic resection of colorectal nonpolypoid lesions., Design: Prospective study., Setting: Single-center teaching hospital., Main Outcome Measurements: Efficacy and safety of the hydro-jet system and rate of complete resection., Results: The system was clinically applied in 31 patients to remove a total of 34 lesions throughout the colon. An adequate submucosal fluid cushion was achieved in all but 1 case without any lifting-associated complications. Complete endoscopic resection was possible in all 33 lifted lesions by using a snare. The size of the resected lesions ranged from 7 to 60 mm. Major intraprocedure bleeding occurred in only 1 case. No perforation or late bleeding was recorded. Histological examination showed a selective accumulation of fluid in the submucosa with edema and dissociation of submucosal structures, with no damage to the muscularis mucosa and very limited "burn effect" hampering assessment of radial margins., Limitations: Lack of controls., Conclusions: This inexpensive system allows safe and rapid submucosal lifting of colorectal nonpolypoid lesions to assist endoscopic resection.

A liquid jet injector employs compressed gas or spring to produce a high-velocity stream to deliver liquid drug into human body through skin. There are many clinical jet injection products available, none of which is domestic. A new liquid jet injector is designed based on a comprehensive analysis of the current products. The injector consists of an ejector, trigger and a re-positioning mechanism. The jets characteristics of sample injector are tested, and the results show that the maximum exit pressure is above 15 MPa, a threshold value for penetrating into the skin.

In this study, the mechanical properties of a self-made jet injector and a foreign product are tested from three aspects: penetration ability, injection completeness and injection dispersion. Correspondingly, three different experiments are designed and performed: dynamic pressure measurement, injection into silicon rubbers with fixed hardness yet different thickness and injection into polyacrylamide gels with fixed hardness. The results show similar mechanical properties between self-made system and the foreign system. The evaluation of the mechanical performance of jet injectors that consists of penetration ability, injection completeness and injection dispersion can describe the jet injection process effectively.