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At least 37 records · Page 2Linked to original sources

Low-volume jet injection for intradermal immunization in rabbits.

BACKGROUND: This study tested a low-volume (20-30 microl/20-30 microg DNA) jet injection method for intradermal delivery of a DNA vaccine. Jet injection offers the advantages of a needle-less system, low-cost, rapid preparation of the injected DNA solution, and a simple delivery system. More than one construct can be injected simultaneously and the method may be combined with adjuvants. RESULTS: Low-volume jet injection targeted delivery of a DNA solution exclusively to the dermis and epidermis of rabbits. A three injection series of plasmid DNA, encoding the Hepatitis B Surface Antigen stimulated a humoral immune response in 2/5 rabbits. One rabbit developed a significant rise in antibody titer after 1 injection and one following 2 injections. There were no significant differences between jet injection and particle bombardment in the maximal antibody titers or number of injections before response. A three injection series of the same plasmid DNA by particle bombardment elicited a significant rise in antibody titer in 3/5 rabbits. One rabbit developed antibody after 1 injection and two after 3 injections. In contrast, 0/5 rabbits receiving DNA by needle and syringe injection responded. In the jet injection and particle bombardment groups, gene expression levels in the skin did not predict response. While immune responses were similar, luciferase gene expression levels in the skin following particle bombardment were 10-100 times higher than jet injection. CONCLUSION: Low-volume jet injection is a simple, effective methodology for intradermal DNA immunization.

Animals↗

Gene transfer by jet injection into differentiated tissues of living animals and in organ culture.

Jet injection can be used to introduce genes into the cells of differentiated tissues of living animals and organ cultures. When a solution of plasmid DNA is jet injected into a selected tissue or organ, cells lying in or near the path of the jet injection are transfected with the DNA and the introduced gene(s) are expressed. Since there is minimal morbidity from each jet injection, multiple injections can be performed at the same or nearby sites. Both mRNA and protein expression from transfected genes can be quantitated using standard methods. In addition, the technique is an efficient means of DNA immunization. Methodology for using jet injection to transfer plasmid DNA into the cells of skin, fat, mammary gland, and muscle are described.

Adipose Tissue↗

Pharmacokinetics and pharmacodynamics of a single dose of recombinant human growth hormone after subcutaneous administration by jet-injection: comparison with conventional needle-injection.

The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers completed an open label, randomised, two-way crossover study, with a 7-day washout period between the two single sc doses. Pharmacokinetic parameters were derived from rhGH concentrations in blood samples collected regularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%-confidence interval 108-142). The AUC0-infinity for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%-confidence interval 93-103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH were associated with identical rhythmical changes in FFA. The study indicates that jet-injected and needle-injected rhGH are bioequivalent with respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter finding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.

Adult↗

Jet-induced skin puncture and its impact on needle-free jet injections: experimental studies and a predictive model.

Needle-free jet injections constitute an important method of drug delivery, especially for insulin and vaccines. This report addresses the mechanisms of interactions of liquid jets with skin. Liquid jets first puncture the skin to form a hole through which the fluid is deposited into skin. Experimental studies showed that the depth of the hole significantly affects drug delivery by jet injections. At a constant jet exit velocity and nozzle diameter, the hole depth increased with increasing jet volume up to an asymptotic value and decreased with increasing values of skin's uniaxial Young's modulus. A theoretical model was developed to predict the hole depth as a function of jet and skin properties. A simplified model was first verified with polyacrylamide gels, a soft material in which the fluid mechanics during hole formation is well understood. Prediction of the hole depth in the skin is a first step in quantitatively predicting drug delivery by jet injection.

Biomechanical Phenomena↗

JET INJECTION.

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Humans↗

Nonviral jet-injection gene transfer for efficient in vivo cytosine deaminase suicide gene therapy of colon carcinoma.

Jet-injection technology has developed into an efficient gene delivery system for nonviral in vivo gene transfer. In this study the jet-injector system was used for the intratumoral gene transfer of small volumes of naked DNA encoding the Escherichia coli cytosine deaminase (CD) suicide gene. In our in vivo studies human colon carcinoma (patient-derived tumor model Colo5734 and SW480 colon carcinoma)-bearing NMRI-nu/nu male mice received four jet injections (10 microl per injection) of the CD-gene-carrying plasmid, representing 40 microg plasmid DNA per animal. Forty-eight hours after jet-injection, treatment of tumors with 5-fluorocytosine (5-FC; 500 mg/kg ip) was started and during treatment tumor volumes were measured. Starting from day 5 of 5-FC treatment inhibition of tumor growth was seen in the CD-gene-transduced tumors compared to the respective control groups, which lasted for the entire observation time. Expression analysis at the mRNA and protein levels revealed efficient expression of the CD gene in the jet-injected tumors. Therefore, in this in vivo study jet-injection gene transfer of 40 microg CD-expressing naked plasmid DNA leads to a significant tumor growth inhibition. This study demonstrates the applicability of the jet-injection technology for in vivo gene transfer into tumors to achieve efficient tumor gene therapy.

Animals↗

Jet injection of insulin vs the syringe-and-needle method.

A new technique of injecting insulin without a needle employs a jet injector to administer a high-pressure stream of medication. This method causes very little pain and affords great accuracy, ease of administration, and safety. The medication is more widely diffused in the body by jet injection than by the needle-and-syringe technique. The control of blood sugar (with similar doses of insulin) achieved by the two techniques is similar, and their effect on local tissues is also similar. In the patients studied, jet injection appeared to be a very satisfactory method of administering insulin and has met with good patient-acceptance. Jet injection is also a useful method for the visually handicapped.

Absorption↗

New way to deliver fluids: endoscopic jet injection into the beagle prostate.

PURPOSE: Local therapy of the prostate could have a role in the treatment of benign prostatic hyperplasia as well as prostate cancer. Endoscopic jet injection could simplify these treatments. We evaluated the tissue effects of endoscopic jet injection in an animal model. MATERIALS AND METHODS: An endoscopic jet injector was developed. In 12 beagle dogs the prostate was injected with single shot and continuous mode jet injection. Macroscopic and histological analysis was performed 0, 2 and 14 days after jet injection. RESULTS: Jet injection allowed complete penetration of the beagle prostate. The single shot technique resulted in only minimal tissue effects. However, the continuous mode led to major tissue damage, even complete aseptic necrosis, in the injected area. CONCLUSIONS: A new method for endoscopic application of fluids is described. Depending on the jet injection technique it could be used to apply pharmaceutical agents or plasmids, and/or induce aseptic necrosis.

Animals↗

Safety, tolerability, and lack of antibody responses after administration of a PfCSP DNA malaria vaccine via needle or needle-free jet injection, and comparison of intramuscular and combination intramuscular/intradermal routes.

Introduction of a new vaccine requires choosing a delivery system that provides safe administration and the desired level of immunogenicity. The safety, tolerability, and immunogenicity of three monthly 2.5-mg doses of a PfCSP DNA vaccine were evaluated in healthy volunteers as administered intramuscularly (IM) by needle, IM by jet injection (Biojector or IM/intradermally (ID) by jet injection. Vaccine administration was well-tolerated. Adverse events were primarily mild and limited to the site of injection (98%). Jet injections (either IM or ID) were associated with approximately twice as many adverse events per immunization as needle IM, but nevertheless were strongly and consistently preferred in opinion polls taken during the study. No volunteers had clinically significant biochemical or hematologic changes or detectable anti-dsDNA antibodies. In conclusion, the injection of Plasmodium falciparum circumsporozoite (PfCSP) DNA vaccine appeared to be safe and well-tolerated when administered by any of the three modes of delivery. However, despite improved antibody responses following both jet injection and ID delivery in animal models, no antibodies could be detected in volunteers by immunofluorescence antibody test (IFAT) or enzyme-linked immunosorbent assay (ELISA) after DNA vaccination.

Animals↗