Home-Use Hyaluronic Acid Jet Injectors: Unreliable and Unsafe.

BACKGROUND: Needle-free hyaluronic acid (HA) jet injectors are gaining popularity for rejuvenation treatment. The devices are widely available online and are used for self-injection or in beauty salons by nonphysicians. However, little is known about their performance and safety. OBJECTIVE: To explore the injection efficiency and cutaneous biodistribution patterns administered with home-use compared with medical jet injectors and to assess safety aspects. MATERIALS AND METHODS: The authors injected HA into ex vivo human skin with 4 home-use and 2 medical injectors. The intracutaneous dose of HA was calculated, and the cutaneous biodistribution of HA was assessed using a 3-dimensional Fluorescent Imaging Cryomicrotome System (3D-FICS). Safety aspects were evaluated based on the presence of a manual, CE (conformité européenne) mark, and sterility. RESULTS: The intracutaneous dose delivered by the home-use injectors was markedly lower compared with the medical injectors. 3D imaging for home-use injectors showed superficial epidermal distribution with low distribution volumes. For medical injectors, volumes were substantially larger and mainly middermal. All evaluated safety aspects were lacking. CONCLUSION: Results of this study suggest that the specific combinations of home-use injectors and HA used in this study are unreliable and unsafe, which casts doubts on the performance of these treatments in general.

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.

A Comparison in Patient Comfort Using Conventional Syringe and Needleless Jet Anesthesia Technique in Periodontal Surgery-A Split-Mouth Randomized Clinical Trial.

Background and Objectives: Periodontal surgery requires local anesthetic coverage to alleviate patient discomfort. Needles and injections can engender feelings of fear and anxiety in individuals. This study aimed to assess the level of comfort and anxiety in patients during the administration of local anesthesia using needleless jet anesthesia (JA) when compared to a conventional syringe (CS) in periodontal surgery. Method and Materials: 60 sites were designated for injection in a split-mouth design in 30 subjects who required periodontal surgery. Local anesthesia was administered in two appointments scheduled one week apart using either a JA system or a CS. The Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), and Beck's anxiety inventory were used to report the pain and anxiety levels while injecting local anesthesia. Statistical analysis of the results was performed using the Shapiro-Wilks test and Paired t-test. Results: Patients reported greater comfort with JA. The VAS and VRS values were statistically significant-(p = 0.003) and (p = 0.001), respectively. Patients showed fear and were nervous about receiving a local anesthetic using a CS. A few subjects experienced lingering pain with the CS, whereas greater comfort and no lingering soreness were reported post-operatively at the site of JA administration. Conclusions: This study provides the first comprehensive assessment of using JA for periodontal surgical procedures. Lower pain scores were consistently observed with the use of jet injectors. Patients were at ease and reported lesser anxiety and greater comfort with jet injectors, making it ideally suited for providing local anesthesia in periodontal surgery.

Subcutaneous nicotine delivery via needle-free jet injection: A porcine model.

Subcutaneous delivery of nicotine was performed using a novel electrically-operated needle-free jet injector, and compared to hypodermic needle delivery in a porcine model. Nicotine was delivered as a single, one-milligram dose into the abdominal skin, formulated as a 50 microliter aqueous solution. Plasma levels of nicotine and cotinine, its main metabolite, were then monitored over 2 h, following which the injection site was excised for histological examination. No irritation or tissue damage were found at the injection sites, and the jet-injected nicotine exhibited comparable absorption into the systemic circulation to that injected using a conventional needle and syringe. The needle-free jet injection of nicotine is a promising and well tolerated method. The data presented from this porcine model will support a first in human trial towards a new promising nicotine replacement therapy.

Needle-free jet versus conventional needle injection for local anesthesia in men undergoing surgical sperm retrieval.

BACKGROUND: Surgical sperm retrieval, requiring local anesthetic injection, is the most frequent surgical procedure in male infertility. However, needle phobia is common and may contribute to negative experiences or refusal of procedures employing needle injection. OBJECTIVES: The aim of this study was to compare the acceptability, safety, and efficacy of needle-free jet anesthetic technique (MadaJet) with conventional needle injection for surgical sperm retrievals in patients with azoospermia. MATERIALS AND METHODS: This single-blind randomized controlled trial (RCT) was included of 59 participants who underwent surgical sperm retrievals. Patients were randomly assigned to the needle-free jet (n = 29) or needle injection (n = 30) groups prior to undergoing the surgery. The primary endpoint was the pain score. RESULTS: Baseline characteristics were comparable between the two groups. The safety and adverse outcomes were also not statistically significant difference (p > 0.05). The pain score in patients using needle-free jet was significantly lower than that in patients using needle injection (p < 0.05). Patients in MadaJet group had a significantly lower discomfort score during (p < 0.001) and after (p = 0.01) injection than those in the needle injection group. However, there was no significant difference in the fear score (before, during, and after) of MadaJet and needle injection (p = 0.98, p = 0.74, and p = 0.94, respectively). The mean time to onset of anesthesia was much shorter in the MadaJet group as compared with needle injection (10 ± 4 vs. 157.5 ± 71 s, p < 0.001). However, the duration of anesthesia in patients using MadaJet was shorter compared with those using needle injection (44 ± 13 vs. 63 ± 26 min, p < 0.001). CONCLUSION: In conclusion, for local anesthesia in patients undergoing surgical sperm retrieval, MadaJet produces less pain and discomfort with quicker time to onset and offset of anesthesia compared with conventional needle injection.

Assessment of anesthetic properties and pain during needleless jet injection anesthesia: a randomized clinical trial

Abstract Pain due to administration of local anesthetics is the primary reason for patients' fear and anxiety, and various methods are used to minimize it. This study aimed to measure the degree of pain during administration of anesthesia and determine the latency time and duration of pulpal anesthesia using two anesthetic methods in the maxilla. Materials and Methods: A randomized, single-blind, split-mouth clinical trial was conducted with 41 volunteers who required class I restorations in the maxillary first molars. Local anesthesia was administered with a needleless jet injection system (experimental group) or with a carpule syringe (control) using a 30-gauge short needle. The method of anesthesia and laterality of the maxilla were randomized. A pulp electric tester measured the latency time and duration of anesthesia in the second molar. Visual analogue scale (VAS) was used to measure the degree of pain during the anesthetic method. Data were tabulated and then analyzed by a statistician. The t-test was used to analyze the differences between the groups for basal electrical stimulation. Duration of anesthesia and degree of pain were compared using the Mann-Whitney test. A 5% significance level was considered. Results: There was no statistical difference in the basal electrical stimulation threshold (mA) and degree of pain between the two methods of anesthesia (p>0.05). Latency time was 2 minutes for all subjects. The duration of pulpal anesthesia showed no statistical difference (minutes) between the two methods (p<0.001), with a longer duration for the traditional method of anesthesia (median of 40 minutes). Conclusions: The two anesthetics methods did not differ concerning the pain experienced during anesthesia. Latency lasted 2 minutes for all subjects; the traditional infiltration anesthesia resulted in a longer anesthetic duration compared with the needleless jet injection.

HybridKnife high-pressure glycerol jet injection for endoscopic submucosal dissection increases procedural ease and speed: a randomised study in pigs and a human case series.

BACKGROUND AND AIMS: Good use of the submucosal space is key during endoscopic submucosal dissection (ESD). High-pressure injection of a long-lasting viscous solution using the HybridKnife water-jet system has been demonstrated to be feasible. We compared jet injection of glycerol and normal saline during pig gastric ESD and assessed its feasibility and efficiency during human ESD. MATERIALS AND METHODS: A blinded randomised controlled study of ESD with the HybridKnife injecting either a glycerol mixture or normal saline and a prospective human case series were performed. Twenty gastric pig dissections (10/group) and 38 human ESDs along the gastrointestinal tract were performed. Dissection speed, specimen size, procedure duration, rates of en bloc and R0 resection, and rates of bleeding and perforation were prospectively recorded. An evaluation of operator comfort and perceived safety (dissection score) was performed using a visual analogue scale with zero being the worst score and ten the best. RESULTS: Dissection was significantly more rapid (1.38-fold) with glycerol injection than with normal saline injection (28.94 vs. 20.91 mm(2)/min; p = 0.037). The dissection score was significantly higher in the glycerol group than in the normal saline group (7.3 vs. 4.7; p = 0.0064). No differences were observed in the rates of en bloc resection, bleeding, or perforation. The 38 human cases along the gastrointestinal tract revealed good results (en bloc resection rate = 100 %, R0 resection rate = 90 %) without any complications. CONCLUSION: High-pressure jet injection of glycerol with the HybridKnife for ESD increased the speed and operator comfort of the procedure compared with the use of normal saline, and the procedure was safe and efficient for human ESD. The advantages of using a combination of the HybridKnife system and a viscous glycerol solution will help to spread the use of the ESD technique, particularly in non-Asian countries.

Jet injection of a monoclonal antibody: A preliminary study.

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.

Optimization of drug viscosity used in gas-powered liquid jet injectors.

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.

High-pressure jet injection of viscous solutions for endoscopic submucosal dissection: a study on ex vivo pig stomachs.

BACKGROUND: Long-lasting lifting is a key factor during endoscopic submucosal dissection (ESD) and can be obtained by water-jet injection of saline solution or by injection of viscous macromolecular solutions. Combination of the jet injection and the macromolecular viscous solutions has never been used yet. We assessed the ability of a new water-jet system to inject viscous solutions in direct viewing and in retroflexion. We compared jet injection of saline solution and hyaluronate 0.5 % to perform ESD on ex vivo pig stomachs in order to evaluate the benefits of macromolecular solutions when injected by a jet-injector system. METHODS: This is a prospective comparative study in pig stomachs. Using the jet injector, four viscous solutions were tested: hydroxyethyl starch, glycerol mix, hyaluronate sodic (0.5 %), and poloxamer mix. Ten ESDs larger than 25 mm (five in direct viewing and five in retroflexion) and one larger than 10 cm were performed with each solution. ESD with hyaluronate jet injection was then compared with ESD with saline jet injection by performing 50 ESDs in each group. A single, minimally-experienced operator conducted all the procedures. RESULTS: All 145 resections were complete, including all marking points with two perforations. Eleven jet ESDs per solution were conducted without any injection issue. In the second part of the study, when compared with saline, significant benefit of hyaluronate was observed on dissection speed (0.80 vs. 1.08 cm(2)/min, p < 0.001). CONCLUSION: This is the first report on a jet-injector system allowing injection of macromolecular viscous solutions even with retroflexed endoscope. Jet injection of macromolecular solutions can speed up dissection in comparison with saline, and should now be tested on humans.

Less painful arterial blood gas sampling using jet injection of 2% lidocaine: a randomized controlled clinical trial.

OBJECTIVE: The aim of this study was to compare pain levels from arterial blood gas (ABG) sampling performed with or without application of lidocaine via jet injector. BACKGROUND: Pain is still a primary concern in the emergency department. Arterial blood gas sampling is a very painful procedure. No better technique for decreasing the pain of the ABG procedure has been presented. An ideal local anesthesia procedure for ABG sampling should be rapid, easily learned, inexpensive, and free of needlestick risk. MATERIALS AND METHODS: We evaluated the effectiveness of a lidocaine jet injection technique in achieving satisfactory pain control in patients undergoing ABG sampling. Forty-two patients were randomized to 2 groups: group A, which received lidocaine by jet injection (0.2 mL of lidocaine 2%), and group B, a control group that received a topical application of 1 mL of lidocaine gel 2% 2 minutes before the ABG sampling. Pain was assessed on a 10-cm visual analog scale (0, absence of pain; 10, greatest imaginable pain). RESULTS: The pain visual analog scale score during ABG sampling was considerably lower in group A compared with group B (1.29 ± 0.90 vs 4.19 ± 1.43; P < .001). The number of attempts required for ABG sampling was significantly lower in group A compared with group B (1.29 ± 0.46 vs 2.1 ± 0.12; P = .009). All residents reported ease of use with the lidocaine jet injection procedure (P < .05). CONCLUSION: Lidocaine jet injection provides beneficial and rapid anesthesia, resulting in less pain and a greater rate of successful ABG sampling. Therefore, it is recommended for use before ABG sampling to decrease the patient's pain and the number of unsuccessful attempts and to enhance the patient's satisfaction.

Jet-injection of short hairpin RNA-encoding vectors into tumor cells.

The use of the RNA interference (RNAi) through the expression of small hairpin RNA (shRNA) is a promising approach for efficient gene silencing for therapeutic applications. In this chapter, we describe the in vivo reversal of the classical MDR1/P-glycoprotein (MDR1/P-gp)-mediated multidrug resistance (MDR) phenotype by shRNA. For local intratumoral delivery of naked shRNA-encoding vector constructs, the nonviral jet-injection was used. This jet-injector system uses compressed air to inject small volumes (5-10 muL) of naked nucleic acid solutions into tumor tissues. Furthermore, the design of the jet-injector allows multiple injections. Under our experimental design, the delivery of plasmid DNA encoding anti-MDR shRNA by jet-injection into human MDR1/P-gp overexpressing MaTu/ADR breast cancer xenografts resulted in a decrease of MDR1 mRNA expression level to more than 90%. Accordingly, the corresponding MDR1/P-gp protein is no longer detectable in the tumors after anti-MDR1 shRNA vector injection. Furthermore, combination of two intratumoral jet-injections of anti-MDR1 shRNA vectors with two intravenous administrations of doxorubicin is sufficient for a complete reversal of the MDR phenotype in association with tumor growth inhibition.

Nonviral jet-injection technology for intratumoral in vivo gene transfer of naked DNA.

The main challenges for application of gene therapy to patients are poor selectivity in vector targeting, insufficient gene transfer, and great difficulties in systemic treatment in association with safety concerns for particular vector systems. For success in gene therapy, safe, applicable, and efficient transfer technologies are required. Because of the complex nature of targeted vector delivery to the tumor, our strategy for gene therapy is focused on the development of local nonviral gene transfer. This approach of local interference with tumor growth and progression could contribute to better control of the disease. Transfer of naked DNA is an important alternative to liposomal or viral systems. Different physical procedures are used for improved delivery of naked DNA into the target cells or tissues in vitro and in vivo. Among the various nonviral gene delivery technologies, jet-injection is gaining increased attractiveness, because this technique allows gene transfer into different tissues with deep penetration of naked DNA by circumventing the disadvantages associated with, e.g., viral vectors. The jet-injection technology is based on jets of high velocity for penetration of the skin and underlaying tissues, associated with efficient transfection of the affected area. The jet-injection technology has been successfully applied for in vivo gene transfer in different tumor models. More importantly, the efficacy and safety of jet-injection gene transfer have recently been investigated in a phase I clinical trial.

Combining DNA technologies and different modes of immunization for induction of humoral and cellular anti-HIV-1 immune responses.

We show here that it is possible to combine two different genetic immunogens, one designed to induce HIV-1 specific humoral immune responses (pKCMVgp160B) and one designed to induce cellular anti-HIV-1 immune responses (Auxo-GTU-MultiHIV), and still retain the major properties of both vaccine constructs. The two different constructs were delivered using two different methods; the gene-gun and the Biojector, which both are needle-free devices. In BALB/c mice we were able to induce high levels of HIV-1-specific T cell responses as well as high levels of anti-gp160 antibodies by co-administrating the vaccine constructs. The cellular immune responses, but not antibody responses, were moderately compromised from the combination. This study shows that it is a feasible strategy to combine different vaccines and modes of delivery, but that interference as to magnitude may occur to certain gene products.

Electrosonic ejector microarray for drug and gene delivery.

We report on development and experimental characterization of a novel cell manipulation device-the electrosonic ejector microarray-which establishes a pathway for drug and/or gene delivery with control of biophysical action on the length scale of an individual cell. The device comprises a piezoelectric transducer for ultrasound wave generation, a reservoir for storing the sample mixture and a set of acoustic horn structures that form a nozzle array for focused application of mechanical energy. The nozzles are micromachined in silicon or plastic using simple and economical batch fabrication processes. When the device is driven at a particular resonant frequency of the acoustic horn structures, the sample mixture of cells and desired transfection agents/molecules suspended in culture medium is ejected from orifices located at the nozzle tips. During sample ejection, focused mechanical forces (pressure and shear) are generated on a microsecond time scale (dictated by nozzle size/geometry and ejection velocity) resulting in identical "active" microenvironments for each ejected cell. This process enables a number of cellular bioeffects, from uptake of small molecules and gene delivery/transfection to cell lysis. Specifically, we demonstrate successful calcein uptake and transfection of DNA plasmid encoding green fluorescent protein (GFP) into human malignant glioma cells (cell line LN443) using electrosonic microarrays with 36, 45 and 50 mum diameter nozzle orifices and operating at ultrasound frequencies between 0.91 and 0.98 MHz. Our results suggest that efficacy and the extent of bioeffects are mainly controlled by nozzle orifice size and the localized intensity of the applied acoustic field.

Influence of solution viscosity and injection protocol on distribution patterns of jet injectors: application to photodynamic tumour targeting.

Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA) and preformed photosensitisers. In this study, we investigated the potential of jet injection to deliver both ALA and a preformed photosensitiser (meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate, TMP) into a defined volume of skin. Initial studies using a model hydrogel showed that as standoff distance is increased, injection depth decreases. As the ejected volume is increased, injection depth increases. It was also shown, for the first time, that, as injection solution viscosity was increased, for a given injection setting and standoff distance, both total depth of jet penetration, L(t), and depth at which the maximum width of the penetration pattern occurred, L(m), decreased progressively. For a standoff distance of zero, the maximum width of the penetration pattern, L(w), increased progressively with increasing viscosity at each of the injection settings. Conversely, when the standoff distance was 2.5 mm, L(w) decreased progressively with increasing viscosity. Studies with neonate porcine skin revealed that an injection protocol comprising an 8.98 mPas solution, an arbitrary injection setting of 8 and a standoff distance of zero was capable of delivering photosensitisers to a volume of tissue (L(t) of 2.91 mm, L(m) of 2.14 mm, L(w) of 5.10 mm) comparable to that occupied by a typical nodular basal cell carcinoma. Both ALA and TMP were successfully delivered using jet injection, with peak tissue concentrations (67.3 mg cm(-3) and 5.6 mg cm(-3), respectively) achieved at a depth of around 1.0mm and substantial reductions in drug concentration seen at depths below 3.0 mm. Consequently, jet injection may be suitable for selective targeting of ALA or preformed photosensitisers to skin tumours.

Intracellular targeting of CEA results in Th1-type antibody responses following intradermal genetic vaccination by a needle-free jet injection device.

The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen) affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector). CEA was expressed either in a membrane-bound form (wild-type CEA) or in two truncated forms (CEA6 and CEA66) with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.

Selective tissue elevation by pressure injection (STEP) facilitates endoscopic mucosal resection (EMR).

Endoscopic mucosal resection and endoscopic submucosal dissection have become more common in treatment of flat superficial tumors of the gastrointestinal tract. Submucosal injection is used to try to avoid complications and improve the technical feasibility of the procedure. However, the method has its limitations, particularly when treating extensive flat tumors in the colon. The water-jet dissector has already demonstrated its capacity for selective cutting with the dissection of parenchymatous. This chapter addresses a new indication, transmucosal mucosal elevation, together with first clinical results. After carrying out animal experiments into the physical properties using animal preparations and freshly resected human specimens from operations, our work group investigated and compared the applicability of the procedure using different carrier fluids. Six test substances-hydroxyethyl starch (HES), Gelafusal, Infukoll, Glucose 50 und isotonic saline solution-were injected into six anesthetized pigs; the height of the submucosal fluid cushion created by the injection was measured endosonographically over a period of 45 minutes. Endoscopic mucosal resection was subsequently carried out, and the resected specimen together with the area it was taken from were assessed histologically. Using commercially available NaCl cartridges, applied by the way of endocapillaries, 18 lesions were elevated in a series of 12 patients and subsequently resected endoscopically. All investigated substances could be applied without difficulty using the Helix HydroJet (Erbe Elektromedizin GmbH, Waldhörnle-Str., Tübingen, Germany). The plasma expanders (HES and Gelafundin 4%, B. Braun Melsungen AG, Melsungen, Germany) produced longer lasting fluid cushions than the isotonic solutions. Mucosal resections could be carried out in all cases with all of the solutions. Histological investigation confirmed the selective nature of the fluid accumulation in the submucosal tissue, which spared the lamina mucosae and lamina muscularis propria. The first clinical applications were successful. The technique of selective fluid accumulation in the submucosa by pressure injection, selective tissue elevation by pressure injection (STEP), presented herein for the first time in a clinical setting, makes it easier to carry out endoscopic mucosal resections and expands the use of this technique to treatment of extended lesions. The manufacturer has announced his intention of combining this technology with an IT-knife, so further improvements can be expected.

Selective fluid cushion in the submucosal layer by water jet: advantage for endoscopic mucosal resection.

BACKGROUND/AIM: Numerous new techniques have recently been reported and described for the endoscopic mucosal resection of large superficial lesions of the gastrointestinal tract. We present here for the first time the application of a water jet dissector for mucosa elevation. MATERIALS AND METHODS: In an ex vivo study, the effectiveness of a water jet dissector (Helix Hydro-Jet) placed directly on the stomach walls of 8 pigs was examined to create a mucosal elevation. After having determined optimal pressures, angle of application, and application times, 13 submucosal fluid cushions were produced in different areas of the stomach walls of 8 pigs in vivo, and the sizes of the resulting submucosal cushions were measured. RESULTS: Using pressures between 30 and 70 bar, it was routinely possible to create submucosal fluid cushions in the stomach wall ex vivo as well as in vivo. Histological examination showed a selective edema in the submucosa without damage to the deeper mucosal layers of the gastric wall. CONCLUSIONS: The capacity of a targeted high-pressure water jet to penetrate the mucosa and selectively create a fluid cushion in the submucosa facilitates endoscopic resection of the mucosa. This new method could contribute to ameliorate the endoscopic treatment of mucosal tumors which previously could not be resected endoscopically due to their size, extent, or location.

Enfuvirtide plasma levels and injection site reactions using a needle-free gas-powered injection system (Biojector).

OBJECTIVES: To assess the use of the Biojector B2000 needle-free gas-powered injection system for subcutaneous administration of enfuvirtide in HIV-infected patients and to compare this system with standard needles and syringes with respect to ease of use, severity of injection site reactions (ISR), and enfuvirtide plasma levels. DESIGN: An observational study among 32 treatment-experienced HIV clinic patients receiving enfuvirtide. METHODS: Adult patients were assessed before and after switching from standard needles to the Biojector for enfuvirtide administration. Patients used the Biojector for up to 24 weeks and rated ease of use from 0 (easy) to 3 (difficult). ISR were graded from 0 to 31 for signs and symptoms (erythema, induration, pruritus, nodules/cysts, ecchymosis), duration of individual lesions, and number of lesions. Plasma was collected pre-dose and 1 h post-dose for enfuvirtide measurement. The high-pressure liquid chromatography with tandem mass spectrometry method used was specific for enfuvirtide over its known plasma metabolite. Wilcoxon rank sum tests were used to compare needle-based and Biojector outcomes. RESULTS: The Biojector was rated as being significantly easier to use (P < 0.001) and reduced the occurrence of ISR compared with standard needles (P < 0.001). Enfuvirtide plasma levels were not statistically different between the two administration methods at either pre-dose trough (P = 0.41) or 1 h post-dose (P = 0.74). CONCLUSIONS: The Biojector needle-free injection system was easy to use for enfuvirtide administration and was associated with a decreased severity of ISR. Plasma enfuvirtide levels pre-dose and 1 h post-dose were comparable when injecting with standard needles or the Biojector.