INJEX50 could improve the success rate of local anesthesia for arterial cannulation in the pediatric intensive care unit: A randomized, double-blind, single-center study.

BACKGROUND: Quick arterial cannulation is required in pediatric emergency situation, which require effective local anesthesia to avoid withdrawal movement. However, pediatric local anesthesia could be difficult because of withdrawal movement. Jet injectors, which are needleless and provide local anesthesia quickly, could be helpful for pediatric local anesthesia during arterial cannulation. AIMS: This study aimed to examine whether new jet injector "INJEX50" could improve the success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with the current standard of care, infiltration using a 26-gauge needle. METHODS: This study was a randomized, double-blind, single-center study. Participants were infants and young children in the pediatric intensive care unit, who required an arterial line. Local anesthesia was performed with either a 26-gauge needle (group C) or INJEX50 (group I) before arterial cannulation. The primary outcome (success of local anesthesia) was the presence of withdrawal movement at the time of skin puncture for arterial cannulation. The secondary outcomes included rescue sedation during arterial cannulation. Data were analyzed using Fisher's exact test and the Mann-Whitney U-test, with values of p < .05 considered statistically significant. RESULTS: Seventy patients were randomly assigned to groups C and I. The local anesthesia success rate in group I (30/35 [86%]) was significantly higher than that in group C (15/35 [43%], odds ratio, 8.00; 95% confidence interval, 2.51-25.5; p = .0005). In conclusion, INJEX50 could improve success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with 26-gauge needle.

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-induced small-droplet aerosol formation during intralesional bleomycin therapy.

OBJECTIVES: Needle-free jet injectors are frequently used in dermatological practice. Injection-generated small-droplet aerosols could be harmful upon inhalation when chemotherapeutics, like bleomycin, are used. Here, we aim to explore jet injector-induced small-droplet aerosol formation of bleomycin in relation to air ventilation and to provide safety measures for clinical practice. MATERIALS AND METHODS: With a professional particle sensor, we measured airborne aerosol particles (0.2-10.0 µm) after electronic pneumatic injection (EPI), spring-loaded jet injection (SLI), and needle injection (NI) of bleomycin and saline (100 µl) on ex vivo human skin. Three levels of air ventilation were explored: no ventilation, room ventilation, and room ventilation with an additional smoke evacuator. RESULTS: EPI and SLI induced significant small-droplet aerosol formation compared with none after NI (0.2-1.0 µm; no ventilation). The largest bleomycin aerosol generation was observed for the smallest particles (0.2-1.0 µm) with 673.170 (528.802-789.453) aerosol particles/liter air (EPI; no ventilation). Room ventilation and smoke evacuation led to a reduction of ≥99% and 100% of measured aerosols, respectively. CONCLUSION: Jet injectors generate a high number of small-droplet aerosols, potentially introducing harmful effects to patients and healthcare personnel. Room ventilation and smoke evacuation are effective safety measures when chemotherapeutics are used in clinical practice.

Clinical endpoints of needle-free jet injector treatment: An in depth understanding of immediate skin responses.

OBJECTIVES: Needle-free jet injectors have been used in dermatological practice for many years. However, predefined clinical endpoints that guide physicians to choose optimal device settings have not been clearly defined. Here, we evaluate immediate skin responses as clinical endpoints for needle-free jet injector treatments. METHODS: We injected methylene blue in ex vivo human skin using an electronically-controllable pneumatic injector (EPI; 3-6 bar, 50-130 µl; n = 63), and a spring-loaded jet injector (SLI) with fixed settings (100 µl; n = 9). We measured the immediate skin papule (3D-camera), residual surface fluid (pipette), dermal dye distribution by estimating depth and width, and subcutaneous dye deposition. RESULTS: EPI with 4 bar and 100 µl resulted in the largest skin papule of 48.7 mm3 (35.4-62.6 mm3 ) and widest dermal distribution of 8.0 mm (5.5-9.0 mm) compared to EPI with 6 bar and 100 µl (p < 0.001, p = 0.018, respectively). The skin papule volume showed a significant moderate to high positive correlation with the width and depth of dye distribution in the dermis (rs = 0.63, rs = 0.58, respectively; p < 0.001 for both correlations). SLI showed high variability for all outcome measures. Finally, a trend was observed that a small skin papule (≤7 mm) and little residual surface fluid (≤10% of injection volume) were warning signs for subcutaneous deposition. CONCLUSIONS: The immediate skin papule and residual surface fluid correspond with dermal drug deposition and are relevant clinical endpoints for needle-free jet injector treatments in dermatological practice.

A one-time pneumatic jet-injection of 5-fluorouracil and triamcinolone acetonide for treatment of hypertrophic scars-A blinded randomized controlled trial.

BACKGROUND: Patients with hypertrophic scars (HTS) risk reduced quality of life due to itching, pain, poor cosmesis, and restriction of movement. Despite good clinical efficacy, patients are often reluctant to undergo repeated needle injections due to pain or needle phobia. OBJECTIVES: To evaluate the applicability of needle-free pneumatic jet injection (PJI) and assess changes in hypertrophic scars following a single PJI treatment with 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC). METHODS: Twenty patients completed this blinded, randomized, controlled, split-scar trial. The intervention side of the HTS received a one-time treatment with PJIs containing a mixture of TAC + 5-FU injected at 5 mm intervals (mean 7 PJI per HTS); the control side received no treatment. Assessments were made at baseline and 4 weeks posttreatment. Outcome measures included change in (1) Vancouver Scar Scale (VSS) total score and subscores, (2) scar volume and surface area assessed by three-dimensional imaging, (3) skin microarchitecture measured by optical-coherence tomography (OCT), (4) photo-assessed scar cosmesis (0-100), (5) patient-reported pain and satisfaction (0-10), and (6) depiction of drug biodistribution after PJI. RESULTS: PJI with TAC + 5-FU significantly decreased both HTS height (-1 VSS; p = 0.01) and pliability (-1 VSS; p < 0.01) with a nonstatistically significant reduction of -1 in total VSS score (0 in control; p = 0.09). On 3D imaging, a 33% decrease in scar volume (p = 0.016) and a 37% decrease in surface area (p = 0.008) was observed. OCT indicated trends towards smoother scar surface (Ra 11.1-10.3; p = 0.61), normalized dermal microarchitecture (attenuation coefficient: 1.52-1.68; p = 0.44), and a reduction in blood flow between 9% and 17% (p = 0.50-0.79). Despite advances in VSS subscores and OCT, no improved photo-assessed cosmesis was found (-3.2 treatment vs. -1.4 control; p = 0.265). Patient-reported pain was low (2/10) and 90% of the patients that had previously received needle injections preferred PJI to needle injection. Depositions of TAC + FU were imaged reaching deep into the scar at levels corresponding to the reticular dermis. CONCLUSION: A single PJI injection containing 5-FU and TAC can significantly improve the height and pliability of HTS. PJI is favored by the patients and may serve as a complement to conventional needle injections, especially for patients with needle phobia.

Jet or conventional local anaesthesia? A randomized controlled split mouth study.

OBJECTIVES: To compare the efficacy, acceptance and preference of conventional infiltration technique with a needleless jet anaesthetic device (Comfort-In). MATERIALS AND METHODS: Non-fearful healthy adult volunteers, aged 19-40 years, were recruited in the Dental School of Aristotle University of Thessaloniki, Greece. Intact maxillary premolars were selected for local anaesthesia. Both techniques were applied sequentially with 35 min time gap on either buccal side on the same day by the same operator. The quadrant and the order of administration were randomly assigned using an online randomization generator. Immediately after administration, at 1, 3, 5, 10, 15, 20, 25 and 30 min, pulp vitality and soft tissue pain reaction tests were performed. Each participant was asked 6 questions in order to assess acceptance. At the end of the session, at 24 h and 7 days, all participants were asked to report any adverse events and their preference. RESULTS: In 63 volunteers who were successfully followed, 63 teeth received conventional local infiltration and 63 the Comfort-In. Both techniques presented with similar anaesthetic efficacy at 1, 3, 5, 10 and 15 min, whereas the conventional technique was more efficacious at 20 min (p < 0.005). Both presented similar acceptance apart from higher pain/discomfort during administration of Comfort-In (p = 0.002). Significantly higher preference was reported for the conventional technique immediately after the session, at 24 h and at 7 days (p < 0.0005); 19 (30.2%) reported the presence of ecchymosis or lacerations at the Comfort-In site as opposed to 5 (7.9%) with the conventional method (p < 0.0001). CONCLUSION: Both techniques showed similar effectiveness. Conventional infiltration was preferred to needleless anaesthesia by non-fearful adult volunteers and was associated with less adverse events. CLINICAL RELEVANCE: This study enhances the advantages of conventional local anaesthesia. TRIAL REGISTRATION: ISRCTN17400733.

Needle-Free Injection Assisted Drug Delivery-Histological Characterization of Cutaneous Deposition.

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.

Hydrothermal Ethanol Flames in Co-Flow Jets.

Results on the autoignition and stabilization of ethanol hydrothermal fames in a Supercritical Water Oxidation (SCWO) reactor operating at constant pressure are reported. The flames are observed as luminous reaction zones occurring in supercritical water; i.e., water at conditions above its critical point (approximately 22 MPa and 374 °C). A co-flow injector is used to inject fuel (inner flow), comprising an aqueous solution ranging from 20 %-v to 50 %-v ethanol, and air (annular flow) into a reactor filled with supercritical water at approximately 24.3 MPa and 425 °C. Results show hydrothermal fames are autoignited and form diffusion flames which exhibit laminar and/or turbulent features depending upon flow conditions. Two orthogonal camera views are used; one providing a backlit shadowgraphic image of the co-flow jet and the other providing color images of the flame. In addition, spectroscopic measurements of flame emissions in the UV and visible spectrum are discussed.

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.

DNA Vaccine Encoding a Modified Hemagglutinin Trimer of Avian Influenza A Virus H5N8 Protects Mice from Viral Challenge.

The development of a safe and effective vaccine against avian influenza A virus (AIV) H5N8 is relevant due to the widespread distribution of this virus in the bird population and the existing potential risk of human infection, which can lead to significant public health concerns. Here, we developed an experimental pVAX-H5 DNA vaccine encoding a modified trimer of AIV H5N8 hemagglutinin. Immunization of BALB/c mice with pVAX-H5 using jet injection elicited high titer antibody response (the average titer in ELISA was 1 × 105), and generated a high level of neutralizing antibodies against H5N8 and T-cell response, as determined by ELISpot analysis. Both liquid and lyophilized forms of pVAX-H5 DNA vaccine provided 100% protection of immunized mice against lethal challenge with influenza A virus A/turkey/Stavropol/320-01/2020 (H5N8). The results obtained indicate that pVAX-H5 has good opportunities as a vaccine candidate against the influenza A virus (H5N8).

Effect of the new needle-free injection system on pain perception and dental anxiety during anesthesia: randomized controlled split-mouth study.

Backgrounds: Pain management is one of the most important factors affecting the success of pediatric dentistry. Therefore, new needle- and pain-free local anesthesia techniques have been developed in parallel with technological advancements. The purpose of this study is to compare the pain perception and dental anxiety levels associated with a needle-free injection system (Comfort-in™) and the classic needle method during treatment-required infiltration anesthesia in children. Methods: This randomized controlled crossover split-mouth clinical study included 94 children who required dental treatment with local anesthesia using a dental needle or needle-free injection system for the bilateral primary molars. The Wong-Baker Scale (WBS) was used to measure pain perception at different times, and the Modified Child Dental Anxiety Scale (MCDAS) was used to measure the anxiety level of the child. A statistical software package was used to process the data. Statistical significance was set at P < 0.05. Results: There was no significant difference between the needle-free injection system and dental needle method during the induction stage for filling and pulpotomy (P > 0.05). "Pain on postoperative 1st day" was similar in both types of anesthesia (P = 0.750). Conclusions: The needle-free injection system was as effective as the dental needle method. The Comfort-in™ system was an acceptable alternative for patients during the postoperative period. Understanding how pain management may be provided during local anesthesia administration and a child's fear and anxiety regarding the dentist may lead to better dental compliance.

Jet-Induced Blood Release From Human Fingertips: A Single-Blind, Randomized, Crossover Trial.

BACKGROUND: Lancet pricks are often poorly received by individuals with diabetes; jet injection may allow lancet-free blood sampling. We examine whether the technique of jet injection can release sufficient blood from the fingertip to enable measurement of blood glucose concentration. In addition, we assess the effect of jet shape and cross-sectional area on fluid release, blood dilution, and perceived pain. METHODS: A randomized, single-blind, crossover study was conducted on 20 healthy volunteers who received interventions on four fingertips: a lancet prick, and jet injection of a small quantity of saline solution through three differently shaped and sized nozzles. Released fluid volume, blood concentration, and glucose concentration were assessed immediately after the intervention. Pain perception and duration, and any skin reactions, were evaluated both immediately and 24 hours after the intervention. RESULTS: Jet injection released sufficient blood from the fingertip to conduct a glucose measurement. A slot-shaped nozzle released the most blood, although less than a lancet, with slightly higher pain. The blood glucose levels estimated from the extracted fluid showed a mean absolute percentage error of 25%. There was no consistent evidence that a jet injection leads to different skin reactions at the intervention site relative to a lancet prick. CONCLUSIONS: Fingertip penetration by jet injection can release a volume of fluid sufficient for blood glucose measurement. Jet injection with a slot-shaped nozzle and/or a nozzle with larger outlet area helps to release more fluid. This technique may enable blood sampling, glucose concentration measurement, and insulin delivery to be performed in a single device.

Minimally invasive capillary blood sampling methods.

INTRODUCTION: Whole blood samples, including arterial, venous, and capillary blood, are regularly used for disease diagnosis and monitoring. The global Covid-19 pandemic has highlighted the need for a more resilient screening capacity. Minimally invasive sampling techniques, such as capillary blood sampling, are routinely used for point of care testing in the home healthcare setting and clinical settings such as the Intensive Care Unit with less pain and wounding than conventional venepuncture. AREAS COVERED: In this manuscript, we aim to provide a overview of state-of-the-art of techniques for obtaining samples of capillary blood. We first review both established and novel methods for releasing blood from capillaries in the skin. Next, we provide a comparison of different capillary blood sampling methods based on their mechanism, testing site, puncture size, cost, wound geometry, healing, and perceptions of pain. Finally, we overview established and new methods for enhancing capillary blood collection. EXPERT OPINION: We expect that microneedles will prove to be a preferred option for paediatric blood collection. The ability of microneedles to collect a capillary blood sample without pain will improve paediatric healthcare outcomes. Jet injection may prove to be a useful method for facilitating both blood collection and drug delivery.

Therapeutic efficacy of metronidazole by needle-free jet injection combined with blue light therapy in Moderate-to-Severe facial acne vulgaris.

BACKGROUND: Acne vulgaris is one of the most common dermatological diseases. Some topical treatments for acne used in combination, such as blue light and topical antibiotics (such as metronidazole) by needle-free jet injection (NFJI), are becoming prevalent in clinical practice, but the efficacy remains uncertain. METHODS: In order to investigate the effect of blue light combined with metronidazole by NFJI in the treatment of acne, the 251 enrolled patients were randomly assigned into the blue light group, metronidazole (MNZ) group, and MNZ + blue light group, and then received 6-weeks' treatment. A variety of objective and subjective methods such as clinical pictures, skin barrier physiological parameters (including trans-epidermal water loss (TEWL), stratum corneum hydration, facail surface sebum, erythema and pigmentation), the Investigator Global Assessment score, acne lesion count assessment, Patients' Self-Assessment, and VAS score were used to evaluate the efficacy and side effects of the treatments. RESULTS: Compared to the baseline, the MNZ + blue light group showed significant improvement in acne lesion count reduction, TEWL, straum corneum hydration, facial surface sebum and erythema (p < 0.05). The MNZ + blue light group showed significant differences compared with the MNZ group and blue light group in terms of acne lesion count reduction and erythema (p < 0.05) Compared to the MNZ group, the MNZ + blue light group demonstrated significant improvement in TEWL and sebum (p < 0.05). While compared to the blue light group, the MNZ + blue light group showed significant improvement in hydration (p < 0.05). There was no statistically significant difference among the three groups in pigmentation (p > 0.05). CONCLUSION: The combination of MNZ by NFJI and blue light has a synergistic effect and can relieve acne skin lesion within 6 weeks in the treatment of moderate and moderate-to-severe facial acne vulgaris, meanwhile, this method has a good safety.

Efficacy and safety of needle-free jet injector-assisted intralesional treatments in dermatology-a systematic review.

Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and safety of these treatments has not been published. The objectives of this study are to evaluate the efficacy and safety of needle-free jet injections for dermatological indications and to provide evidence-based treatment recommendations. An electronic literature search was conducted in April 2022. Two reviewers independently selected studies based on predefined criteria and performed a methodological quality assessment using the Cochrane Collaborations risk-of-bias 2.0 assessment tool and Newcastle-Ottawa Scale. Thirty-seven articles were included, involving 1911 participants. Dermatological indications included scars, alopecia areata, hyperhidrosis, nail diseases, non-melanoma skin cancer, common warts, local anesthesia, and aesthetic indications. Keloids and other types of scars (hypertrophic, atrophic, and burn scars) were investigated most frequently (n = 7). The included studies reported favorable efficacy and safety outcomes for intralesional jet injector-assisted treatment with triamcinolone acetonide/hexacetonide, 5-fluorouracil, bleomycin, or hyaluronic acid. Two high-quality studies showed good efficacy and tolerability of intralesional jet injections with a combination of 5-fluorouracil and triamcinolone acetonide in hypertrophic scars and with saline in boxcar and rolling acne scars. No serious adverse reactions and good tolerability were reported in the included studies. Overall, the methodological quality of the included studies was low. Limited evidence suggests that needle-free jet injector-assisted intralesional treatment is efficacious and safe for hypertrophic and atrophic acne scars. More well-powered RCTs investigating the efficacy and safety of jet injector treatment in dermatology are warranted to make further evidence-based recommendations.

Vacuum-Assisted Needle-Free Capillary Blood Sampling.

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.

Determining Losses in Jet Injection Subcutaneous Insulin Delivery: A Model-Based Approach.

OBJECTIVE: Accurate, safe glycemic management requires reliable delivery of insulin doses. Insulin can be delivered subcutaneously for action over a longer period of time. Needle-free jet injectors provide subcutaneous (SC) delivery without requiring needle use, but the volume of insulin absorbed varies due to losses associated with the delivery method. This study employs model-based methods to determine the expected proportion of active insulin present from a needle-free SC dose. METHODS: Insulin, C-peptide, and glucose assay data from a frequently sampled insulin-modified oral glucose tolerance test trial with 2U SC insulin delivery, paired with a well-validated metabolic model, predict metabolic outcomes for N = 7 healthy adults. Subject-specific nonlinear hepatic clearance profiles are modeled over time using third-order basis splines with knots located at assay times. Hepatic clearance profiles are constrained within a physiological rate of change, and relative to plasma glucose profiles. Insulin loss proportions yielding optimal insulin predictions are then identified, quantifying delivery losses. RESULTS: Optimal parameter identification suggests losses of up to 22% of the nominal 2U SC dose. The degree of loss varies between subjects and between trials on the same subject. Insulin fit accuracy improves where loss greater than 5% is identified, relative to where delivery loss is not modeled. CONCLUSIONS: Modeling shows needle-free SC jet injection of a nominal dose of insulin does not necessarily provide metabolic action equivalent to total dose, and this availability significantly varies between trials. By quantifying and accounting for variability of jet injection insulin doses, better glycemic management outcomes using SC jet injection may be achieved.

DNA Aß42 immunization via needle-less Jet injection in mice and rabbits as potential immunotherapy for Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia found in the elderly and disease progression is associated with accumulation of Amyloid beta 1-42 (Aß42) in brain. An immune-mediated approach as a preventive intervention to reduce amyloid plaques without causing brain inflammation is highly desirable for future clinical use. Genetic immunization, in which the immunizing agent is DNA encoding Aß42, has great potential because the immune response to DNA delivered into the skin is generally non-inflammatory, and thus differs quantitatively and qualitatively from immune responses elicited by peptides, which are inflammatory with production of IFNγ and IL-17 cytokines by activated T cells. DNA immunization has historically been proven difficult to apply to larger mammals. A potential barrier to use DNA immunization in large mammals is the method for delivery of the DNA antigen. We tested jet injection in mice and rabbits and found good antibody production and safe immune responses (no inflammatory cytokines). We found significant reduction of amyloid plaques and Aß peptides in brains of the DNA Aß42 immunized 3xTg-AD mouse model. This study was designed to optimize DNA delivery for possible testing of the DNA Aß42 vaccine for AD prevention in a clinical trial.

A Scientometric Analysis and Visualization of Scientific Research and Technology Innovation in Needle-free Insulin Injection From 1974 to 2022.

PURPOSE: Needle-free jet injection has to some extent improved the quality of life of patients with diabetes, but it has not been widely used. Therefore, we analyzed articles, clinical trials, and patents of needle-free insulin injection to (1) perform a systematic and comprehensive analysis of scientific research and technology innovation in needle-free insulin injection during the past 49 years (1974 to 2022) and (2) identify the status of scientific research and technology innovation, their limitations, and future trends. METHODS: With a new perspective, we use scientometric tools, including co-word and word frequency analyses, text mining, and cluster network analysis, to provide a scientometric analysis and visualization of articles, clinical trials, and patents related to needle-free insulin injection delivery applications. FINDINGS: Patent innovation in this field was more active than clinical research, and clinical research prevailed over basic research. Basic research and clinical trials in this field mainly involved therapy, penetration, tolerability, absorption, and pharmacokinetic properties. Drive mechanisms and needle-free injection devices were the core patent technologies in this field. IMPLICATIONS: Although needle-free insulin injection has been under development for decades, its full potential has not yet been reached; needle-free injection technology is still in the growth stage. The field of needleless insulin injection is dominated by patent technology innovation.

Dynamic interaction of injected liquid jet with skin layer interfaces revealed by microsecond imaging of optically cleared ex vivo skin tissue model.

BACKGROUND: Needle-free jet injection (NFJI) systems enable a controlled and targeted delivery of drugs into skin tissue. However, a scarce understanding of their underlying mechanisms has been a major deterrent to the development of an efficient system. Primarily, the lack of a suitable visualization technique that could capture the dynamics of the injected fluid-tissue interaction with a microsecond range temporal resolution has emerged as a main limitation. A conventional needle-free injection system may inject the fluids within a few milliseconds and may need a temporal resolution in the microsecond range for obtaining the required images. However, the presently available imaging techniques for skin tissue visualization fail to achieve these required spatial and temporal resolutions. Previous studies on injected fluid-tissue interaction dynamics were conducted using in vitro media with a stiffness similar to that of skin tissue. However, these media are poor substitutes for real skin tissue, and the need for an imaging technique having ex vivo or in vivo imaging capability has been echoed in the previous reports. METHODS: A near-infrared imaging technique that utilizes the optical absorption and fluorescence emission of indocyanine green dye, coupled with a tissue clearing technique, was developed for visualizing a NFJI in an ex vivo porcine skin tissue. RESULTS: The optimal imaging conditions obtained by considering the optical properties of the developed system and mechanical properties of the cleared ex vivo samples are presented. Crucial information on the dynamic interaction of the injected liquid jet with the ex vivo skin tissue layers and their interfaces could be obtained. CONCLUSIONS: The reported technique can be instrumental for understanding the injection mechanism and for the development of an efficient transdermal NFJI system as well.