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At least 19 recordsLinked to original sources

Gene transfer into mammalian cells by jet injection.

Jet injection of DNA in solution is a technique that can be used to transfer DNA into tissues of living animals, where the introduced genes are expressed. The muscle, fat, skin, and mammary tissue of mice, and the fat, skin, and mammary tissue of sheep can be transfected with DNA. A jet injector, such as the Ped-o-jet (Stirn Industries, Dayton, NJ), is used to form a jet from 100 to 300 microliters of a DNA solution. This jet has sufficient force to travel into and through tissues of adult and juvenile animals. The introduced DNA is found in cells surrounding the path of the jet. When jet injection is performed through the surface of intact skin, underlying muscle, mammary, and fat, cells up to 2 cm distant from the point of injection are transfected with DNA. In this study, we demonstrate that the efficiency of DNA transfer is dependent upon the force of injection. Jet injection is an alternative to needle injection, lipofection, and particle bombardment for the introduction of "naked" DNA into the tissues of animals. This technique has potential for the introduction of genes into living organisms for genetic vaccination and gene therapy.

Animals↗

Dental analgesia by jet injection.

Jet injection is a procedure of introducing anaesthetic solution into the tissues without the use of the hypodermic needle. This is accomplished by forcing the solution under high pressure from a minute orifice in the form of a high velocity jet.

Anesthesia, Dental↗

Trigger point injections vs. jet injection in the treatment of myofascial pain.

Trigger point injections using dilute solutions of local anesthetic agents have proved effective for many patients with myofascial pain. The treatment itself, however, can produce severe pain and may occasionally be associated with complications. It was determined in this study that a local anesthetic solution administered by jet injection in the area of myofascial trigger points was capable of providing short-term pain relief equal to conventional trigger point injections using a hypodermic needle and syringe. The jet injector system produced significantly less pain during treatment than conventional trigger point injections and therefore was preferred by most subjects having the opportunity to compare both forms of treatment.

Adult↗

Needle-free jet injections: dependence of jet penetration and dispersion in the skin on jet power.

Jet injection is a needle-free drug delivery method in which a high-speed stream of fluid impacts the skin and delivers drugs. Although a number of jet injectors are commercially available, especially for insulin delivery, a quantitative understanding of the energetics of jet injection is still lacking. Here, we describe the dependence of jet injections into human skin on the power of the jet. Dermal delivery of liquid jets was quantified using two measurements, penetration of a radiolabeled solute, mannitol, into skin and the shape of jet dispersion in the skin which was visualized using sulforhodamine B (SRB). The power of the jet at the nozzle was varied from 1 to 600 W by independently altering the nozzle diameter (30-560 microm) and jet velocity (100-200 m/s). The dependence of the amount of liquid delivered in the skin and the geometric measurements of jet dispersion on nozzle diameter and jet velocity was captured by a single parameter, jet power. Additional experiments were performed using a model material, polyacrylamide gel, to further understand the dependence of jet penetration on jet power. These experiments demonstrated that jet power also effectively describes gel erosion due to liquid impingement.

Drug Delivery Systems↗

Uptake, biodistribution, and time course of naked plasmid DNA trafficking after intratumoral in vivo jet injection.

Nonviral jet injection is an applicable technology for in vivo gene transfer of naked DNA. However, little is known about the biodistribution and clearance of jet-injected DNA, or about its localization within tissue and cells. Therefore, in this study we analyzed the intratumoral and systemic biodistribution of jet-injected naked DNA in human colon carcinoma-bearing NCr-nu/nu mice, which were jet-injected with the pCMVbeta plasmid DNA. Intratumoral and systemic plasmid DNA biodistribution was analyzed 5, 10, 20, and 40 min and 3, 6, 24, 48, and 72 hr after jet injection, using quantitative real-time polymerase chain reaction. In the tumors, a rapid drop in naked DNA load within 24 hr of jet injection was shown. Detailed analysis of intratumoral distribution of rhodamine-labeled DNA revealed the presence of plasmid DNA within tumor cells 5 min after jet injection and further accumulation of significant DNA amounts in the cell nuclei 30 to 60 min after jet injection. In the blood, DNA amounts rapidly dropped within 10 to 40 min of jet injection to less than 0.001 pg of plasmid per 250 ng of tissue DNA and only minimal plasmid DNA dissemination was detected in liver, lung, spleen, kidney, and ovaries, which was cleared 3 to 6 hr after jet injection. By contrast, in heart, bone marrow, and brain almost no plasmid DNA was detectable.

Animals↗

Jet injection into polyacrylamide gels: investigation of jet injection mechanics.

Jet injectors employ high-velocity liquid jets that penetrate into human skin and deposit drugs in the dermal or subdermal region. Although jet injectors have been marketed for a number of years, relatively little is known about the interactions of high-speed jets with soft materials such as skin. Using polyacrylamide gels as a model system, the mechanics of jet penetration, including the dependence of jet penetration on mechanical properties, was studied. Jets employed in a typical commercial injector, (orifice diameter: 152 microm, velocity: 170-180 m/s) were used to inject fluid into polyacrylamide gels possessing Young's moduli in the range of 0.06-0.77 MPa and hardness values in the range of 4-70 H(OO). Motion analysis of jet entry into polyacrylamide gels revealed that jet penetration can be divided into three distinct events: erosion, stagnation, and dispersion. During the erosion phase, the jet removed the gel at the impact site and led to the formation of a distinct cylindrical hole. Cessation of erosion induced a period of jet stagnation ( approximately 600 micros) characterized by constant penetration depth. This stage was followed by dispersion of the liquid into the gel. The dispersion took place by crack propagation and was nearly symmetrical with the exception of injections into 10% acrylamide (Young's modulus of 0.06 MPa). The penetration depth of the jets as well as the rate of erosion decreased with increasing Young's modulus. The mechanics of jet penetration into polyacrylamide gels provides an important tool for understanding jet injection into skin.

Acceleration↗

Delivery of recombinant adeno-associated virus by jet injection.

The jet-injection technology was used for delivery of recombinant adeno-associated virus (rAAV). Although AAV-based vectors are an attractive tool in gene therapy, some methodological and technical problems of their targeted delivery remain to be solved. We tried to address some of these cell-targeting problems by using a new low-volume needleless injection device the Swiss Injector. First we tested, by electron microscopy, whether jet-injection would have any detrimental effect on rAAV particle integrity. Second, we compared transgene expression after infection of 293T cells with fired or control (non-fired) rAAV that expressed the green fluorescent protein (GFP), beta-galactosidase (beta-gal), the B7.1 molecule, and interleukin 2 (IL2). Third, an rAAV carrying the genes coding for beta-gal was jet-injected into mouse subcutaneous (s.c.) tumours. The staining of tumour cryosections revealed beta-gal expression 72 h after the delivery. Our study demonstrated the applicability of the Swiss Injector for the delivery of rAAV into tumour tissue without either vector particle integrity or the level of expression of the transgenes, as tested in vitro, being affected. The jet-injection technology could improve the distribution of vector particles in the tumour mass without leakage of liquid from the injection site.

Animals↗

Nonviral in vivo gene delivery into tumors using a novel low volume jet-injection technology.

The jet-injection technology has developed as an applicable alternative to viral or liposomal gene delivery systems. In this study a novel, low-volume, 'high-speed jet injector' hand-held system was used for the direct gene transfer of naked DNA into tumors. Lewis-lung carcinoma bearing mice were jet-injected with the beta-galactosidase (LacZ), the green fluorescence (GFP) or the human tumor necrosis factor alpha (TNF-alpha) gene carrying vector plasmids. The animals received five jet injections into the tumor at a pressure of 3.0 bar, delivering 3--5 microl plasmid DNA (1 microg DNA/microl in water) per single jet injection. The jet injection of DNA leads to a widespread expression pattern within tumor tissues with penetration depths of 5--10 mm. Analysis of tumor cryosections revealed moderate LacZ or GFP expression at 48 h and strong reporter gene expression 72 h and 96 h after jet injection. The simultaneous jet injection of the TNF-alpha and LacZ carrying vectors demonstrated efficient expression and secretion of both the cytokine, as well as LacZ expression within the tumor 24 h, 48 h, 72 h, 96 h and 120 h after jet injection. These studies demonstrate the applicability of jet injection for the efficient in vivo gene transfer into tumors for nonviral gene therapy of cancer using minimal amounts of naked DNA.

Animals↗

Diphtheria-tetanus-pertussis immunization by intradermal jet injection.

An intradermal jet injector was used to administer combined diphtheria, tetanus, and pertussis (D.T.P.) vaccines to infants aged 2 to 12 months. A second dose was given one month after the first and a third six months after the second. Each dose was considerably smaller than the standard intramuscular dose. Blood samples taken one month after the third dose showed a satisfactory diphtheria and tetanus antitoxin response in all but a few cases. The antibody response to the pertussis component was not examined. Reactions were insignificant. Intradermal jet injection is proposed as a cheap, extremely rapid, and effective technique for D.T.P. immunization, especially suitable for use in remote areas where trained staff and facilities are few and many children require immunization.

Antibody Formation↗

Intercostal nerve block by jet injection.

A jet injector was used to perform intercostal nerve block as a method of intra-operative and postoperative pain relief at cholecystectomy, using a concentrated solution of local analgesic. This method was shown to be as successful as the conventional needle technique. The risk of pneumothorax, and the problems of the local analgesic solution used are discussed.

Adult↗

Subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection.

To assess the feasibility of jet injection for mass immunization against hepatitis B virus, inactivated, alum-adsorbed hepatitis B vaccine (Merck, Sharp, and Dohme Research Laboratories, West Point, PA) was administered subcutaneously by automatic jet injection to 19 volunteers lacking antibody to hepatitis B surface antigen (anti-HBs). Three 20-microgram doses were given at 0, 1, and 6 months. Of 19 volunteers, 5 (26%) developed anti-HBs by 1 month after the first injection, and 15 of 19 (79%) were anti-HBs-positive 6 to 8 weeks after the first booster administration. Following the second booster, 16 of 19 (84%) recipients had detectable anti-HBs. Possible systemic reactions were limited to low-grade fever (37.8 degrees C) in one volunteer following one injection, and mild lethargy in a second recipient. Local reactions to jet injection of vaccine occurred more frequently, with indurated, nodular lesions 3-10 mm in diameter developing at the site of 19 of 57 (33%) vaccine injections, compared with 2 of 57 (3%) saline placebo injections. Such nodules were generally painless. Sore arms were noted in 11 of 57 (19%) vaccine injections. With the exception of frequent but minor local reactions, subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection is safe, and results in vaccine immunogenicity approximating that associated with intramuscular needle injection.

Adult↗

Needle-free liquid jet injections: mechanisms and applications.

Liquid jet injections employ a high-speed jet to puncture the skin and deliver drugs without the use of a needle. They have been used to deliver a number of macromolecules including vaccines and insulin, as well as small molecules, such as anesthetics and antibiotics. This article reviews liquid jet injectors with respect to their historical perspective, clinical applications, mechanisms and future prospects. An overview of the use of jet injectors for delivery of vaccines, insulin and growth hormones is presented. Particular attention is paid to the mechanistic understanding of jet injections, especially the dependence of jet penetration on parameters such as nozzle diameter, velocity and jet power. Finally, gaps in the current understanding are presented and suggestions for future research and development are made.

Biomechanical Phenomena↗

Low-volume jet injection for efficient nonviral in vivo gene transfer.

The transfer of naked deoxyribonucleic acid (DNA) represents an alternative to viral and liposomal gene transfer technologies for gene therapy applications. Various procedures are employed to deliver naked DNA into the desired cells or tissues in vitro and in vivo, such as by simple needle injection, particle bombardment, in vivo electroporation or jet injection. Among the various nonviral gene delivery technologies jet injection is gaining increasing acceptance because it allows gene transfer into different tissues with deeper penetration of the applied naked DNA. The versatile hand-held Swiss jet injector uses pressurized air to force small volumes of 3 to 10 microL of naked DNA into targeted tissues. The beta-galactosidase (LacZ) reporter gene construct and tumor necrosis factor alpha gene-expressing vectors were successfully jet injected at a pressure of 3.0 bar into xenotransplanted human tumor models of colon carcinoma. Qualitative and quantitative expression analysis of jet injected tumor tissues revealed the efficient expression of these genes in the tumors. Using this Swiss jet-injector prototype repeated jet injections of low volumes (3-10 microL) into one target tissue can easily be performed. The key parameters of in vivo jet injection such as jet injection volume, pressure, jet penetration into the tumor tissue, DNA stability have been defined for optimized nonviral gene therapy. These studies demonstrate the applicability of the jet injection technology for the efficient and simultaneous in vivo gene transfer of two different plasmid DNAs into tumors. It can be employed for nonviral gene therapy of cancer using minimal amounts of naked DNA.

Animals↗

Posterior segment injury developed after injection of anesthetics on eyelids with needleless jet injection device.

BACKGROUND: Though a needleless jet injection device (NJI device) has advantages over a conventional needle attached syringe for injecting anesthetics, safety of using it for lid surgery is not proved. We report a case of posterior segment injury suspected caused by a NJI device. METHODS: A 47-year-old woman presented with decreased visual acuity after regional anesthesia at the lower eyelids with a NJI device. RESULTS: Vitreous and subretinal hemorrhage was found associated with retinal edema adjacent to the optic disc of the right eye and around the inferior temporal arcade of the left eye. Fluorescein angiography revealed choroidal rupture in the both eyes. By 2 months, although the hemorrhage resolved, subretinal fibrosis and chorioretinal atrophy developed. Her vision decreased to 20/60 in the right eye and 20/40 in the left eye. CONCLUSION: The energy generated by the NJI device seemed to have reached the eyeballs to cause the blunt-typed posterior segment injuries. As choroidal rupture may result in a permanent visual loss, the risks associated the off-labeled use of the device for lid surgeries should be awakened.

Anesthesia, Local↗

Intratumoral low-volume jet-injection for efficient nonviral gene transfer.

Jet-injection has become an applicable technology among other established nonviral delivery systems, such as particle bombardment or in vivo electroporation. The low-volume jet injector employed in this study uses compressed air to inject solutions of 1.5-10 microL containing naked DNA into the desired tissue. The novel design of this prototype makes multiple jet-injections possible. Therefore, repeated jet-injections into one target tissue can be performed easily. This jet-injector hand-held system was used for the direct in vivo gene transfer of plasmid DNA into tumors to achieve efficient expression of reporter genes (beta-galactosidase, green fluorescent protein [GFP]) and of therapeutic genes (TNF-alpha) in different tumor models. The study presented here revealed the key parameters of efficient in vivo jet-injection (jet-injection volume, pressure, jet penetration, DNA stability) to define the optimal conditions for a jet-injection-aided nonviral gene therapy.

Animals↗

Smallpox vaccination by intradermal jet injection. I. Introduction, background and results of pilot studies.

Jet injection has met with great success in the rapid and effective mass administration of several immunizing agents. The recent development of a jet injector nozzle specifically designed for intradermal inoculation suggested the possible extension of jet injector methodology to mass smallpox vaccination. A total of 156 volunteer subjects, 16 unvaccinated and 140 vaccinated more than 5 years previously, received either undiluted smallpox vaccine by the multiple-pressure technique, or 0.1 ml of various dilutions of smallpox vaccine by jet injector using the new nozzle. Cutaneous and serological responses in revaccinees revealed that jet injection of diluted vaccine with a titre of 10(7) TCID(50)/ml was as effective as multiple-pressure inoculation of undiluted vaccine. Among the small number of primary vaccinees, jet injection of diluted vaccine with a titre of 10(6) TCID(50)/ml appeared as effective as multiple-pressure inoculation of undiluted vaccine. No complications of vaccination occurred.The findings confirm the utility of the intradermal nozzle for jet injection of smallpox vaccine. In view of the speed of administration and the economy of vaccine, it is suggested that there is a distinct role for jet injection in global smallpox eradication efforts. Further studies on larger numbers of unvaccinated subjects and on persons with significant residual vaccinial immunity are needed to define the optimal concentration of vaccine for mass vaccination by jet injection.

Animals↗