2011 Feb 9. [Epub ahead of print]
Micro-Shock Waves Mediated Needle-less Vaccine Delivery.
Jagadeesh G, Divya Prakash G, Rakesh SG, Allam US, Gopala Krishna M, Eswarappa SM, Chakravortty D.
Department of Aerospace Engineering, Indian Institute of Science, Bangalore-560012, India; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore-560012, India.
Abstract
Shock waves are one of the most efficient mechanisms of energy dissipation, observed in nature. In this study, utilizing the instantaneous mechanical impulse generated behind the micro-shock wave during controlled explosion, a novel non-intrusive needleless vaccine delivery system has been developed. It is well established, that antigens in the epidermis are efficiently presented by resident Langerhans cells, eliciting the requisite immune response, making them a good target for vaccine delivery. Unfortunately, needle free devices for epidermal delivery have inherent problems from the perspective of patient safety and comfort. The penetration depth of less than 100 μm in the skin can elicit higher immune response without any pain. Here we show the efficient utilization of our device for micro-shock wave mediated vaccination. The production of liquid jet was confirmed with high speed microscopy and the penetration in acrylamide gel and mouse skin was observed by confocal microscopy. Salmonella enterica serovar Typhimurium vaccine strain pmrG-HM-D (DV-STM-07) was delivered using our device in the murine salmonellosis model and the effectiveness of the delivery system for vaccination was compared with other routes of vaccination. Our device mediated vaccination elicits better protection as well as IgG response even in lower vaccine dose (ten-fold lesser), in comparison to other routes of vaccination. We anticipate our novel method can be utilized for the effective, cheap and safe vaccination in the near future.
PMID: 21307276 [PubMed - as supplied by publisher]
2010 Oct 28;28(46):7373-80. Epub 2010 Sep 17.
Needle-free jet injection of small doses of Japanese encephalitis DNA and inactivated vaccine mixture induces neutralizing antibodies in miniature pigs and protects against fetal death and mummification in pregnant sows.
Imoto J, Ishikawa T, Yamanaka A, Konishi M, Murakami K, Shibahara T, Kubo M, Lim CK, Hamano M, Takasaki T, Kurane I, Udagawa H, Mukuta Y, Konishi E.
Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Abstract
Japanese encephalitis (JE) virus causes abortion and stillbirth in swine, and encephalitis in humans and horses. We have previously reported that immunogenicity of a DNA vaccine against JE was synergistically enhanced in mice by co-immunization with a commercial inactivated JE vaccine (JEVAX) under a needle-free injection system. Here, we found that this immunization strategy was also effective in miniature pigs. Because of the synergism, miniature pigs immunized twice with a mixture of 10 μg of DNA and a 1/100 dose of JEVAX developed a high neutralizing antibody titer (1:190 at 90% plaque reduction assay). Even using 1 μg of DNA, 3 of 4 pigs developed neutralizing antibodies. Following challenge, all miniature pigs with detectable neutralizing antibodies were protected against viremia. Pregnant sows inoculated with 10 or 1 μg of DNA mixed with JEVAX (1/100 dose) developed antibody titers of 1:40-1:320. Following challenge, fetal death and mummification were protected against in DNA/JEVAX-immunized sows.
Copyright © 2010 Elsevier Ltd. All rights reserved.
PMID: 20851083 [PubMed - indexed for MEDLINE]
2010 Sep;184(3):978-83.
No-needle local anesthesia for adult male circumcision.
Peng Y, Masson P, Li PS, Chang Y, Tian L, Lee R, Kim H, Sokal DC, Goldstein M.
Department of Sexual Medicine, Yijishan Hospital-Wannan Medical College, Wuhu, People's Republic of China.
Abstract
PURPOSE: We used a local anesthetic jet injection technique for adult male circumcision. This method eliminates needle use and may decrease the fear of local anesthetic injection used for male circumcision.
MATERIALS AND METHODS: We recruited 60 men seeking voluntary adult male circumcision into the study from June to September 2009. We used a MadaJet Medical Injector to deliver a high pressure spray of 0.1 ml 2% plain lidocaine solution directly through the penile skin circumferentially around the proximal third of the penis. All men underwent circumcision using the Shang Ring and were evaluated for anesthetic safety, efficacy and acceptability. Pain was measured on a visual analog scale.
RESULTS: The average volume of 2% lidocaine anesthetic solution delivered by jet injection was 0.1 ml with a mean total of 0.9 ml per circumcision procedure. More than 85% of men did not require supplemental anesthesia. Anesthetic onset required approximately 45 seconds from the time that injections were completed. Mean pain scores for immediate postoperative, 24-hour postoperative, ring removal and post-ring removal events were 0.1, 6.8, 2.2 and 0.9, respectively. In 4 patients (6.67%) mild urethral bleeding resolved with pressure, resulting in technique modification.
CONCLUSIONS: No-needle jet injection is safe and effective for adult MC. The technique efficiently delivers local anesthesia with rapid onset in men undergoing circumcision. This needle-free approach may enhance the popularity of adult male circumcision.
2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID: 20643441 [PubMed - indexed for MEDLINE]
2010 Sep;88(9):368.
Needle-free vaccination in sheep.
CSIRO Livestock Industries, Armidale, New South Wales 2350, Australia. Ian.Colditz@csiro.au
Abstract
Multi-dose vaccinators have been in use for many years to vaccinate livestock. A number of needle-free vaccinators that use compressed gas to drive the vaccine through intact skin have been recently introduced to the market. We recently examined the efficacy of a needle-free vaccinator to induce antibodies to tetanus toxoid in sheep. The result indicates that needle-free vaccination can stimulate antibody responses comparable to conventional needle vaccination.
PMID: 20726975 [PubMed - indexed for MEDLINE]
2010 Aug 16;6(16):1785-93.
Targeted, needle-free vaccinations in skin using multilayered, densely-packed dissolving microprojection arrays.
Raphael AP, Prow TW, Crichton ML, Chen X, Fernando GJ, Kendall MA.
The University of Queensland Australian Institute for Bioengineering and Nanotechnology (AIBN) Brisbane, QLD 4072, Australia.
Abstract
Targeting of vaccines to abundant immune cell populations within our outer thin skin layers using miniaturized devices-much thinner than a needle and syringe, could improve the efficacy of vaccines (and other immunotherapies). To meet this goal, a densely packed dissolving microprojection array (dissolving Nanopatch) is designed, achieving functional miniaturization by 1) formulating small microneedles (two orders of magnitude smaller than a standard needle and syringe) and 2) multiple layering of the payload within microprojections with tight tolerances (of the order of a micrometer). The formulation method is suitable to many vaccines because it is without harsh or complex chemical processes, and it is performed at low temperatures and at a neutral pH. When the formulated dNPs are applied to skin, consistent and robust penetration is achieved, rapidly targeting the skin strata of interest (<5 min; significantly faster than larger dissolving microneedles that have been previously reported). Resultant diffusion is significantly enhanced within the dermis compared with the epidermis. Using two different antigens (ovalbumin and a commercial trivalent influenza vaccine [Fluvax2008]), the administration of these dissolving patches generate robust systemic immune responses in a mouse model. To the authors' knowledge, this is the first report of successful vaccination with any form of dissolving microneedles. The patches made by this method therefore have the potential for pain-free, needle-free, and effective vaccination in humans.
PMID: 20665628 [PubMed - indexed for MEDLINE]
2010 Oct;10(10):699-711.
Needle-free influenza vaccination.
Amorij JP, Hinrichs WLj, Frijlink HW, Wilschut JC, Huckriede A.
Department of Pharmaceutical Technology and Biopharmacy, University of Gröningen, Netherlands.
Erratum in:
- Lancet Infect Dis.2010 Nov;10(11):740.
Abstract
Vaccination is the cornerstone of influenza control in epidemic and pandemic situations. Influenza vaccines are typically given by intramuscular injection. However, needle-free vaccinations could offer several distinct advantages over intramuscular injections: they are pain-free, easier to distribute, and easier to give to patients, and their use could reduce vaccination costs. Moreover, vaccine delivery via the respiratory tract, alimentary tract, or skin might elicit mucosal immune responses at the site of virus entry and better cellular immunity, thus improving effectiveness. Although various needle-free vaccination methods for influenza have shown preclinical promise, few have progressed to clinical trials-only live attenuated intranasal vaccines have received approval, and only in some countries. Further clinical investigation is needed to help realise the potential of needle-free vaccination for influenza.
Copyright © 2010 Elsevier Ltd. All rights reserved.
PMID: 20883966 [PubMed - indexed for MEDLINE]
2010;(197):193-219.
Needle-free vaccine injection.
Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Building 75-Cnr of College and Cooper Road The University of Queensland Brisbane, Brisbane, QLD4072, Australia. m.kendall@uq.edu.au
Abstract
Millions of people die each year from infectious disease, with a main stumbling block being our limited ability to deliver vaccines to optimal sites in the body. Specifically, effective methods to deliver vaccines into outer skin and mucosal layers--sites with immunological, physical and practical advantages that cannot be targeted via traditional delivery methods--are lacking. This chapter investigates the challenge for physical delivery approaches that are primarily needle-free. We examine the skin's structural and immunogenic properties in the context of the physical cell targeting requirements of the viable epidermis, and we review selected current physical cell targeting technologies engineered to meet these needs: needle and syringe, diffusion patches, liquid jet injectors, and microneedle arrays/patches. We then focus on biolistic particle delivery: we first analyze engineering these systems to meet demanding clinical needs, we then examine the interaction of biolistic devices with the skin, focusing on the mechanical interactions of ballistic impact and cell death, and finally we discuss the current clinical outcomes of one key application of engineered delivery devices--DNA vaccines.
PMID: 20217531 [PubMed - indexed for MEDLINE]
2010 Spring;57(1):3-12.
Comparison of acceptance, preference, and efficacy between jet injection INJEX and local infiltration anesthesia in 6 to 11 year old dental patients.
Arapostathis KN, Dabarakis NN, Coolidge T, Tsirlis A, Kotsanos N.
Department of Pediatric Dentistry, School of Dentistry, Aristotle University of Thessaloniki, Greece. koarap@dent.auth.gr
Abstract
Needleless devices have been developed to provide anesthesia without injections. Little controlled research has examined the acceptability of needleless devices in pediatric patients. The aims of the study were to compare children's acceptance and preference for one type of needleless jet injection with classical local infiltration as well as to evaluate the efficacy of the needleless anesthesia. Eighty-seven nonfearful children with no previous experience of dental anesthesia were studied using a split-mouth design. The first dental procedure was performed with the classical infiltration anesthesia. The same amount of anesthetic was administered using the INJEX needleless device in a second session 1 week later, during which a second dental procedure was performed. Patients rated their acceptance and preference for the 2 methods, and the dentist recorded data about the need for additional anesthesia. More negative experiences were reported for the INJEX method. Most (73.6%) of the children preferred the traditional method. Among the 87 treatment procedures attempted following the use of INJEX, 80.5% required additional anesthesia, compared with 2.3% of those attempted following traditional infiltration. Traditional infiltration was more effective, acceptable, and preferred, compared with the needleless INJEX.
PMID: 20331333 [PubMed - indexed for MEDLINE]PMCID: PMC2844236Free PMC Article
2010 Oct 28;28(46):7373-80. Epub 2010 Sep 17.
Needle-free jet injection of small doses of Japanese encephalitis DNA and inactivated vaccine mixture induces neutralizing antibodies in miniature pigs and protects against fetal death and mummification in pregnant sows.
Imoto J, Ishikawa T, Yamanaka A, Konishi M, Murakami K, Shibahara T, Kubo M, Lim CK, Hamano M, Takasaki T, Kurane I, Udagawa H, Mukuta Y, Konishi E.
Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Abstract
Japanese encephalitis (JE) virus causes abortion and stillbirth in swine, and encephalitis in humans and horses. We have previously reported that immunogenicity of a DNA vaccine against JE was synergistically enhanced in mice by co-immunization with a commercial inactivated JE vaccine (JEVAX) under a needle-free injection system. Here, we found that this immunization strategy was also effective in miniature pigs. Because of the synergism, miniature pigs immunized twice with a mixture of 10 μg of DNA and a 1/100 dose of JEVAX developed a high neutralizing antibody titer (1:190 at 90% plaque reduction assay). Even using 1 μg of DNA, 3 of 4 pigs developed neutralizing antibodies. Following challenge, all miniature pigs with detectable neutralizing antibodies were protected against viremia. Pregnant sows inoculated with 10 or 1 μg of DNA mixed with JEVAX (1/100 dose) developed antibody titers of 1:40-1:320. Following challenge, fetal death and mummification were protected against in DNA/JEVAX-immunized sows.
Copyright © 2010 Elsevier Ltd. All rights reserved.
PMID: 20851083 [PubMed - indexed for MEDLINE]
2008 Aug;24(8):511-5.
Jet Injection of 1% buffered lidocaine versus topical ELA-Max for anesthesia before peripheral intravenous catheterization in children: a randomized controlled trial.
Spanos S, Booth R, Koenig H, Sikes K, Gracely E, Kim IK.
Division of Pediatric Emergency Medicine and Department of Pediatrics, Kosair Children's Hospital, KY, USA. stephaniespanos@hotmail.com
Abstract
BACKGROUND: Peripheral intravenous (PIV) catheter insertion is a frequent, painful procedure that is often performed with little or no anesthesia. Current approaches that minimize pain for PIV catheter insertion have several limitations: significant delay for onset of anesthesia, inadequate anesthesia, infectious disease exposure risk from needlestick injuries, and patients' needle phobia.
OBJECTIVE: Comparison of the anesthetic effectiveness of J-Tip needle-free jet injection of 1% buffered lidocaine to the anesthetic effectiveness of topical 4% ELA-Max for PIV catheter insertion.
METHODS: A prospective, block-randomized, controlled trial comparing J-Tip jet injection of 1% buffered lidocaine to a 30-minute application of 4% ELA-Max for topical anesthesia in children 8 to 15 years old presenting to a tertiary care pediatric emergency department for PIV catheter insertion. All subjects recorded self-reported visual analog scale (VAS) scores for pain at time of enrollment and pain felt following PIV catheter insertion. Jet injection subjects also recorded pain of jet injection. Subjects were videotaped during jet injection and PIV catheter insertion. Videotapes were reviewed by a single blinded reviewer for observer-reported VAS pain scores for jet injection and PIV catheter insertion.
RESULTS: Of the 70 children enrolled, 35 were randomized to the J-Tip jet injection group and 35 to the ELA-Max group. Patient-recorded enrollment VAS scores for pain were similar between groups (P = 0.74). Patient-recorded VAS scores were significantly different between groups immediately after PIV catheter insertion (17.3 for J-Tip jet injection vs 44.6 for ELA-Max, P < 0.001). Blinded reviewer assessed VAS scores for pain after PIV catheter insertion demonstrated a similar trend, but the comparison was not statistically significant (21.7 for J-Tip jet injection vs 31.9 ELA-Max, P = 0.23).
CONCLUSION: J-Tip jet injection of 1% buffered lidocaine provided greater anesthesia than a 30-minute application of ELA-Max according to patient self-assessment of pain for children aged 8 to 15 years undergoing PIV catheter insertion.
PMID: 18645542 [PubMed - indexed for MEDLINE]
2008 Apr 24;26(18):2186-90. Epub 2008 Mar 17.
Superiority of needle-free transdermal plasmid delivery for the induction of antigen-specific IFNgamma T cell responses in the dog.
Goubier A, Fuhrmann L, Forest L, Cachet N, Evrad-Blanchard M, Juillard V, Fischer L.
Merial S.A.S., R&D, Laboratoire de Lyon Gerland, Lyon, France.
Abstract
Although successful needle-free DNA vaccination has been described on several occasions, the true benefit of this delivery technology over needle-based injections for DNA vaccination of dogs has not yet been documented. We conducted a side-by-side comparison of needle-free transdermal plasmid delivery vs. intramuscular vs. intradermal needle-based delivery of the same plasmid in dogs. Our data confirmed the importance of the route of plasmid delivery and further established the unique potential of needle-free transdermal plasmid delivery to elicit strong antigen-specific, hTyr-specific IFNgamma T in the dog. Further, this study demonstrated that properly enabled DNA vaccination has the potential to trigger very significant cell-based immune responses in dogs, establishing needle-free transdermal plasmid delivery as a critical technology for successful immunotherapy of cancer and/or chronic infectious diseases in companion animal medicine.
PMID: 18395307 [PubMed - indexed for MEDLINE]
2007;14(27):2898-910.
A needle-free approach for topical immunization: antigen delivery via vesicular carrier system(s).
Mahor S, Gupta PN, Rawat A, Vyas SP.
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishwavidyalaya, Sagar - 470003 (MP), India.
Abstract
Topical immunization (TI) is novel and needle free strategy involving vaccine delivery through topical application of antigen and adjuvant(s) directly or via a suitable carrier system on intact skin. Anatomy and physiology of skin attracts scientists in developing topical carrier system(s) for enhanced delivery of bioactive(s). Numerous techniques i.e. physical, chemical and vesicular carrier systems have been exploited for topical immunization. The present review discuss various vesicular systems i.e. liposomes, niosomes, transfersomes, vesosomes etc. for the efficient topical delivery of various immunogens along with comparative points of their merit(s) in TI. The mechanism of permeation of bioactive(s) through skin route via these carriers to the immune system for development of both cellular and humeral immunity has also been discussed. Moreover, the effect of composition and type of carrier system on type of immunity induced has also been focused to develop new effective carrier system(s) for topical immunization.
PMID: 18045135 [PubMed - indexed for MEDLINE]
2007 Aug;30(8):297-303.
[Needle-free injection--science fiction or comeback of an almost forgotten drug delivery system?].
[Article in German]
Abstract
The first to create a "needle-free injector" was the American anesthetist Robert A. Hingson, 65 year ago. Since that time those devices underwent a changeful history. In 1986 an outbreak of hepatitis B among patients receiving injections from a needle-free multiple-use-nozzle injector was documented and related to the use of the injector device. Due to such risk of transmission of infection with these reusable devices, their application has been restricted. In 1998 the WHO recommended that only conventional needles and syringes should be used for immunization until safe needle-free injectors are identified through independent safety testing. Since needle-free injection has shown numerous advantages in comparison to conventional injection, new systems were developed that combine the advantages of needle-free injection with sufficient safety in mass vaccination programs. As an alternative to this early injector type, the disposable-cartridge injectors were developed. The newest research field in the area of the needle-free injection systems opened with the development of powder injectors, in which the drug preparation is no longer a suspension or solution, but a powdered solid. This injector type using powder formulations shows a number of advantages in comparison with the conventional needle/syringe injection technique as well as towards the liquid jet injectors. Due to this new kind of injectors the comeback of the needle-free injection technique in large-scale vaccination programs of the WHO seems reasonable and within reach.
PMID: 17879809 [PubMed - indexed for MEDLINE]
2007 Nov-Dec;38(10):E572-6.
Needle-less local anesthesia: clinical evaluation of the effectiveness of the jet anesthesia Injex in local anesthesia in dentistry.
Dabarakis NN, Alexander V, Tsirlis AT, Parissis NA, Nikolaos M.
Department of Oral Surgery, Implantology, and Roentgenology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece. nikosd@dent.auth.gr
Abstract
OBJECTIVES: To clinically evaluate the jet injection Injex (Rösch AG Medizintechnik) using 2 different anesthetic solutions, and to compare the jet injection and the standard needle injection techniques.
METHOD AND MATERIALS: Of the 32 patients in the study, 10 received mepivacaine 3% anesthetic solution by means of the jet injection technique, while the remaining 22 patients received lidocaine 2% with epinephrine 1:80,000 by the same method. The 14 patients in whom pulp anesthesia was achieved were selected for an additional evaluation of the pulp reaction using standard needle injection anesthesia. The differences between the 2 compounds with Injex were statistically evaluated by means of independent-samples t test analysis. The differences between subgroups receiving both jet injection and needle injection anesthesia were evaluated by means of paired t test analysis.
RESULTS: The administration of mepivacaine 3% using Injex did not achieve pulp anesthesia in any of the 10 patients, although the soft tissue anesthesia was successful. The administration of lidocaine with epinephrine using Injex resulted in pulp anesthesia in only 14 patients; soft tissue anesthesia was observed in all patients of this group. There was no statistically significant difference between Injex and the needle injection technique in onset of anesthesia. However, the duration of anesthesia was significantly longer for the needle infiltration group than for the Injex injection group.
CONCLUSION: The anesthetic solution should be combined with a vasoconstriction agent when the Injex technique is implemented.
PMID: 18197315 [PubMed - indexed for MEDLINE]
2007 Sep;4(5):459-74.
Needle-free vaccine delivery.
Netherlands Vaccine Institute, Research and Development Department, PO Box 457, 3720 Al Bilthoven, The Netherlands. gideon.kersten@nvi-vaccin.nl
Abstract
The need for minimally invasive delivery methods is urgent. As the number of registered vaccines increases, so does the number of injections. The use of sharps can be unsafe and needle immunisation is less suitable for mass immunisations during emergencies such as pandemics or bioterrorist attacks. The approach of combining vaccines has limitations due to high development costs, risk of pharmaceutical or immunological interference and economic risks. Advancements in the development of alternatives to injection with syringes and needles are discussed in this paper, and include: mucosal vaccination, injection without needles and vaccine delivery via the skin.
PMID: 17880271 [PubMed - indexed for MEDLINE]
2007 Jun 12;7:987-99.
Intracellular targeting of CEA results in Th1-type antibody responses following intradermal genetic vaccination by a needle-free jet injection device.
Johansson S, Ek M, Wahren B, Stout R, Liu M, Hallermalm K.
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Abstract
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.
PMID: 17619780 [PubMed - indexed for MEDLINE]
2007 Mar 13;104(11):4255-60. Epub 2007 Mar 6.
Needle-free delivery of macromolecules across the skin by nanoliter-volume pulsed microjets.
Arora A, Hakim I, Baxter J, Rathnasingham R, Srinivasan R, Fletcher DA, Mitragotri S.
Biomolecular Science and Engineering, University of California, Santa Barbara, CA 93106, USA.
Abstract
Needle-free liquid jet injectors were invented >50 years ago for the delivery of proteins and vaccines. Despite their long history, needle-free liquid jet injectors are not commonly used as a result of frequent pain and bruising. We hypothesized that pain and bruising originate from the deep penetration of the jets and can potentially be addressed by minimizing the penetration depth of jets into the skin. However, current jet injectors are not designed to maintain shallow dermal penetration depths. Using a new strategy of jet injection, pulsed microjets, we report on delivery of protein drugs into the skin without deep penetration. The high velocity (v >100 m/s) of microjets allows their entry into the skin, whereas the small jet diameters (50-100 mum) and extremely small volumes (2-15 nanoliters) limit the penetration depth ( approximately 200 mum). In vitro experiments confirmed quantitative delivery of molecules into human skin and in vivo experiments with rats confirmed the ability of pulsed microjets to deliver therapeutic doses of insulin across the skin. Pulsed microjet injectors could be used to deliver drugs for local as well as systemic applications without using needles.
PMID: 17360511 [PubMed - indexed for MEDLINE]PMCID: PMC1838589
2006 Sep;3(5):565-74.
Needle-free liquid jet injections: mechanisms and applications.
Unilever Research and Development, 40 Merritt Blvd., Trumbull, CT 06611, USA. joybaxter@gmail.com
Abstract
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.
PMID: 17064242 [PubMed - indexed for MEDLINE]
2006;127:91-105.
Needle-free delivery of veterinary DNA vaccines.
van Drunen Littel-van den Hurk S, Babiuk S, Babiuk LA.
Vaccine and Infectious Disease Organization, University of Saskatchewan, Sakatoon, Saskatchewan, Canada.
Abstract
Currently, there are a number of obstacles barring effective immunization of large animal species with DNA-based vaccines. Generally, large concentrations of DNA and multiple doses are required before an effective immune response is detected. To overcome these impediments we have developed approaches to deliver the plasmids via needle-free methods, which have been shown to be more effective than traditional needle and syringe methods. Furthermore, we will describe the delivery of vaccines to mucosal surfaces. The procedures described will use sheep and cattle as model veterinary species.
PMID: 16988449 [PubMed - indexed for MEDLINE]
2006;127:83-9.
Needle-free injection of DNA vaccines: a brief overview and methodology.
Viral Diseases Department, Naval Medical Research Center, Silver Spring, MD, USA.
Abstract
The development of needle-free injection originally stemmed from a general apprehension of needle injections, disease transmission by accidental needle-sticks, and the need for effective mass immunization. Naked DNA vaccines, as attractive and universal as they appear, have not produced robust immune responses in test systems. However, proof of principle for DNA vaccines has been validated with a number of vaccine candidates in a variety of test systems, and the concept of DNA vaccines as a generic platform for vaccines still remains viable and attractive. Many avenues are being explored to enhance the immunogenicity of DNA vaccines. The easiest and most straightforward approach that can be quickly transitioned to a clinical trial setting is vaccine delivery by a needle-free jet injector. This approach has shown much potential in a number of cases and should become the lead method for enhancing DNA vaccines. This approach requires no additional development, and with an expanding market and willingness from jet injector manufacturers to produce prefilled syringes, the technique should become feasible for larger phase II/phase III trials.
PMID: 16988448 [PubMed - indexed for MEDLINE]
2006 Summer;19(2):250-9.
Evaluation of a needle-free delivery platform for prime-boost immunization with DNA and modified vaccinia virus ankara vectors expressing herpes simplex virus 2 glycoprotein D.
Laboratory of DNA Viruses, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20852, USA.
Abstract
A previous report described a prime-boost immunization strategy using plasmid and modified vaccinia virus Ankara (MVA) vectors expressing herpes simplex virus 2 glycoprotein D (gD). Enhanced humoral and cellular immune responses were elicited by the prime-boost combination compared to plasmid DNA immunization alone. Surprisingly, a more diverse antibody isotype response, and a greater antibody and cellular immune response, was obtained if the gD MVA vector was used as the priming immunization rather than the gD plasmid vector. The present report evaluates the use of a needle-free delivery platform (Biojector) for delivery of plasmid and MVA gD-expressing vectors in a prime-boost immunization strategy. Needle-free delivery of both plasmid and MVA gD expression vectors was efficient, reproducible, and elicited a strong immune response in immunized mice. Biojector delivery of plasmid DNA was able to evoke a broader isotype response and cellular immune response than that obtained by gene gun delivered plasmid DNA. Further, DNA priming by Biojector delivery as part of a prime-boost procedure with MVA-gD2 resulted in a diverse antibody isotype distribution and enhanced cellular immune responses, similar to the responses obtained when MVA-gD2 was used as the priming immunization. Thus, needle-free delivery of plasmid DNA may provide additional flexibility and options for effective prime-boost vaccination.
PMID: 16817767 [PubMed - indexed for MEDLINE]
2006 Apr 20;58(1):68-89. Epub 2006 Mar 24.
Needle-free vaccine delivery.
Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore Street, Room 480, Baltimore, MD 21201, USA. egiudice@peds.umaryland.edu
Abstract
The search for methods of vaccine delivery not requiring a needle and syringe has been accelerated by recent concerns regarding pandemic disease, bioterrorism, and disease eradication campaigns. Needle-free vaccine delivery could aid in these mass vaccinations by increasing ease and speed of delivery, and by offering improved safety and compliance, decreasing costs, and reducing pain associated with vaccinations. In this article, we summarize the rationale for delivery of needle-free vaccines and discuss several methods currently in use and under development, focusing on needle-free injection devices, transcutaneous immunization, and mucosal immunization. Jet injectors are needle-free devices that deliver liquid vaccine through a nozzle orifice and penetrate the skin with a high-speed narrow stream. They generate improved or equivalent immune responses compared with needle and syringe. Powder injection, a form of jet injection using vaccines in powder form, may obviate the need for the "cold chain." Transcutaneous immunization involves applying vaccine antigen and adjuvant to the skin, using a patch or "microneedles," and can induce both systemic and mucosal immunity. Mucosal immunization has thus far been focused on oral, nasal, and aerosol vaccines. Promising newer technologies in oral vaccination include using attenuated bacteria as vectors and transgenic plant "edible" vaccines. Improved knowledge regarding the immune system and its responses to vaccination continues to inform vaccine technologies for needle-free vaccine delivery.
PMID: 16564111 [PubMed - indexed for MEDLINE]
2006;63(12):1304-9.
[Comparison of the systems used for providing local anesthesia in dentistry--the Wand (Milestone Scientific) and Injex (Rosch)].
[Article in Polish]
Zarzecka J, Gończowski K, Kesek B, Darczuk D, Zapała J.
Pracownia Stomatologii Zachowawczej z Endodoncja, Instytut Stomatologii. Uniwersytetu Jagiellolńskiego Collegium Medicum, Kraków.
Abstract
Local anesthesia is one of the basic and the most often executed interventions in dentistry. This procedure is very stressful for the patients because it is combined with pain. The new systems for delivering local anesthesia in dentistry have revolutionized the technique considerably by its simplify as well as reduction in pain.
THE AIM: this study presents the comparison between the local anesthesia delivery systems used in dentistry--The Wand and Injex, taking into consideration pain intensity during performing anesthesia and the intensification of fear before executed anesthesia with the given system.
MATERIAL AND METHODS: the Visual Analogue Scale (VAS), verbal scale and questionnaires were used to evaluate pain and fear.
RESULTS: On the basis of our investigations it can be concluded that there were statistically important differences between men and women in fear intensity combined with the anesthesia procedure--men were less afraid than women. The patients who were anaesthetized with system The WAND declared less fear before similar anesthesia in future. The average value of intensity of pain analyzed with both verbal and visual scales during anaesthetizing with the system Injex (independently from sex) was statistically significantly higher than for system The WAND--respectively 0.57 and 8.55 for The WAND, 2.02 and 32.18 for Injex (p = 0.001).
CONCLUSION: on the basis of the results of this study it can be concluded that the less stressful and painful local anesthesia delivery system is the WAND.
PMID: 17642145 [PubMed - indexed for MEDLINE]
2006 Feb;102(2):411-4.
A comparison of a needle-free injection system for local anesthesia versus EMLA for intravenous catheter insertion in the pediatric patient.
Jimenez N, Bradford H, Seidel KD, Sousa M, Lynn AM.
Department of Anesthesiology and Pain Medicine, Children's Hospital and Regional Medical Center, University of Washington School of Medicine, Seattle, WA 98105, USA. nathalia.jimenez@seattlechildrens.org
Abstract
Placement of IV catheters is a painful and stressful procedure for children. J-Tip is a needle-less Food and Drug Administration approved injection system that can be used for delivery of local anesthetic before IV cannulation. In this study, we compared the effectiveness of J-Tip versus eutectic mixture of local anesthetics (EMLA) to facilitate IV cannulation and provide adequate analgesia before IV placement. Children 7-19 years of age (n = 116) were randomized to receive 0.25 mL of 1% buffered lidocaine with J-Tip (n = 57) or 2.5 g of EMLA (n = 59) before IV cannulation. Measurements of success of cannulation (number of attempts for IV placement) and pain (0-10 visual analog scale) at application of local anesthetic and at cannulation were performed. There was a significant (P = 0.0001) difference in pain ratings during IV cannulation between EMLA (median = 3) and the J-Tip (median = 0). Eighty-four percent of patients reported no pain at the time of J-Tip lidocaine application compared to 61% in the EMLA group at the time of dressing removal (P = 0.004). We did not find differences in the number of attempts for IV cannulation. J-Tip application of 1% buffered lidocaine before IV cannulation is not painful and has better anesthetic effectiveness compared with EMLA.
PMID: 16428534 [PubMed - indexed for MEDLINE]
2006;39(14):2593-602. Epub 2005 Nov 8.
The penetration of a soft solid by a liquid jet, with application to the administration of a needle-free injection.
Shergold OA, Fleck NA, King TS.
Cambridge University Engineering Department, Trumpington St., Cambridge, CB2 1PZ, UK.
Abstract
Liquid jet injections have been performed on human skin in vivo and silicone rubber using Intraject needle-free injectors. The discharge characteristics of the liquid jet were measured using a custom-built test instrument. The experiments reveal that a high-speed liquid jet penetrates a soft solid by the formation and opening of a planar crack. The fluid stagnation pressure required for skin penetration decreases with increasing diameter of the liquid jet. These findings are consistent with the slow-speed penetration of a soft solid by a sharp-tipped punch. It is demonstrated that the Shergold-Fleck sharp-tipped punch penetration model [Shergold, O.A., Fleck, N.A., 2004. Mechanisms of deep penetration of soft solids. Proc. Roy. Soc. Lond. A 460, 3037-3058.] gives adequate predictions for the pressure required to penetrate a soft solid by a high-speed liquid jet.
PMID: 16277987 [PubMed - indexed for MEDLINE]
2006 Feb;102(2):411-4.
A comparison of a needle-free injection system for local anesthesia versus EMLA for intravenous catheter insertion in the pediatric patient.
Jimenez N, Bradford H, Seidel KD, Sousa M, Lynn AM.
Department of Anesthesiology and Pain Medicine, Children's Hospital and Regional Medical Center, University of Washington School of Medicine, Seattle, WA 98105, USA. nathalia.jimenez@seattlechildrens.org
Abstract
Placement of IV catheters is a painful and stressful procedure for children. J-Tip is a needle-less Food and Drug Administration approved injection system that can be used for delivery of local anesthetic before IV cannulation. In this study, we compared the effectiveness of J-Tip versus eutectic mixture of local anesthetics (EMLA) to facilitate IV cannulation and provide adequate analgesia before IV placement. Children 7-19 years of age (n = 116) were randomized to receive 0.25 mL of 1% buffered lidocaine with J-Tip (n = 57) or 2.5 g of EMLA (n = 59) before IV cannulation. Measurements of success of cannulation (number of attempts for IV placement) and pain (0-10 visual analog scale) at application of local anesthetic and at cannulation were performed. There was a significant (P = 0.0001) difference in pain ratings during IV cannulation between EMLA (median = 3) and the J-Tip (median = 0). Eighty-four percent of patients reported no pain at the time of J-Tip lidocaine application compared to 61% in the EMLA group at the time of dressing removal (P = 0.004). We did not find differences in the number of attempts for IV cannulation. J-Tip application of 1% buffered lidocaine before IV cannulation is not painful and has better anesthetic effectiveness compared with EMLA.
PMID: 16428534 [PubMed - indexed for MEDLINE]Free Article
2005 Dec;5(12):905-16.
Immunization without needles.
Department of Chemical Engineering, University of California, Santa Barbara, California 93106, USA. samir@engineering.ucsb.edu
Abstract
Most current immunization procedures make use of needles and syringes for vaccine administration. With the increase in the number of immunizations that children around the world routinely receive, health organizations are beginning to look for safer alternatives that reduce the risk of cross-contamination that arises from needle reuse. This article focuses on contemporary developments in needle-free methods of immunization, such as liquid-jet injectors, topical application to the skin, oral pills and nasal sprays.
PMID: 16239901 [PubMed - indexed for MEDLINE]
2005 Aug;5(4):467-77.
Use of needle-free injection systems to alleviate needle phobia and pain at injection.
University of Texas Medical School, MSB 5020. 6431 Fannin, Houston, TX 77030, USA. peter.szmuk@uth.tmc.edu
Abstract
Needle phobia affects at least 10% of the general population. Subcutaneous injections are used for many reasons, including immunizations, administration of medications such as insulin and heparin, and to provide local anesthesia, both for surgery and for intravenous cannulation. Whatever the reason for its application, the injection itself may cause discomfort and/or pain. In children, in patients with needle phobia, in those who require frequent intravenous cannulations, or in those who need daily medication, the pain at injection can reach unbearable intensity that could lead to refusal of medical care. Various approaches are employed to alleviate the pain caused by intravenous cannulation. These include the use of topical analgesia [i.e., EMLA, Ametop (tetracaine], Numby Stuff and ethylchloridespray], skin infiltration with lidocaine using 25-30-gauge needles and jet injectors. This article will review the complex topic of needle phobia and needle pain, and will summarize the currently available alternatives and the new developments intended to reduce the intensity of injection pain.
PMID: 19807264 [PubMed]
2005 Sep 2;106(3):361-73.
Jet-induced skin puncture and its impact on needle-free jet injections: experimental studies and a predictive model.
Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA.
Abstract
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.
PMID: 16002174 [PubMed - indexed for MEDLINE
2004;59(3):149-55.
[Clinical evaluation of the INJEX system, a local anesthesia system without needles: a comfort evaluation study].
[Article in French]
Geenen L, Marks LA, Martens LC.
Centre de Médecine Dentaire, Spécialisée, Professeur à L'Université de Gand.
Abstract
The use of needless local anaesthesia systems in dentistry can be of a help in treating needle phobia patients. The aim of this comfort study was to compare a classical local infiltration anaesthesia with a needle-free system. INJEX (ROSCH AG Germany). A split mouth design study was performed. All patients in this study needed 2 restorations. In order to receive objective information on both systems needle-phobia patients were banned. Therefore the first restoration was performed with the classical system (with needle) and the well-acceptance was evaluated. The second restoration was done with the needle-free system. Both patient and dental practitioner performed an evaluation after each treatment. Evaluation by the patient was given by a questionnaire on the comfort of the treatment using Faces Pain Scale, Lickert Scale and a modified version of the Abbreviated Acceptability Rating Profile. By the dental practitioner the comfort of the treatment and the amount of local anaesthesia needed was evaluated. The study was approved by the ethical committee of Ghent University Hospital Belgium. CONCLUSION: The INJEX system can be a valuable alternative to use in paediatric dentistry, although non needle phobia patients in this study did not preferred the needle free INJEX system above the classical local injection.
PMID: 15526641 [PubMed - indexed for MEDLINE]
Publication Types, MeSH Terms, Substances
2004 Mar;150(3):455-61.
Assessment of the biological performance of the needle-free injector INJEX using the isolated porcine forelimb.
Wagner S, Dues G, Sawitzky D, Frey P, Christ B.
Vitro-Tec Entwicklungs-GmbH, Wiesenweg 10, D-12247 Berlin, Germany. wagner@vitro-tec.de
Abstract
BACKGROUND: The development and utilization of novel needle-free injection devices in order to minimize needle stick injuries make increasing demands for suitable assay systems, which reflect the physiological situation in humans as close as possible.
OBJECTIVES: It was therefore the goal of the present study to test the biological performance of a needle-free injector (INJEX) by the use of porcine skin as a model with a high predictive value for the feasibility in humans because of its close similarity to human skin.
METHODS: In order to use porcine skin in the context of the underlying tissues, the isolated porcine forelimb was chosen as an assay model for use with the INJEX injector. Ink or the fluorescent dye fluorescein-isothiocyanate was injected and the penetration depth was determined metrically and dye distribution histologically. To assess the resorption of heparin, needle injection was compared with needle-free injection in a perfused limb model.
RESULTS: Increasing amounts of ink increasingly penetrated into subcutaneous tissue layers in a cone-shaped manner mainly following lead structures. Penetration was hampered by skin thickness and by the deep muscle fascia, which served as a penetration barrier. Resorption of heparin was similar irrespective of injection by the use of a needle or the INJEX device.
CONCLUSIONS: The isolated porcine forelimb serves as a versatile tool for the assessment of the biological performance of needle-free injection devices such as INJEX. Further studies are necessary to correlate the model for drug delivery in humans.
PMID: 15030327 [PubMed - indexed for MEDLINE
2003 Dec;8(6):992-8.
Needle-free topical electroporation improves gene expression from plasmids administered in porcine skin.
Babiuk S, Baca-Estrada ME, Foldvari M, Baizer L, Stout R, Storms M, Rabussay D, Widera G, Babiuk L.
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada. babiuks@sask.usask.ca
Abstract
Electroporation has been shown to increase the potency of DNA vaccines that have demonstrated significant potential in mice. However, there is a need to develop noninvasive or minimally invasive vaccination methods. In pigs, in vivo gene expression was assessed to compare intradermal needle injection to a needle-free dermal BioJect as a means of delivery of plasmids. Each administration method was further tested with and without surface electroporation. Experiments with plasmid DNA encoding luciferase demonstrated that needle-free administration results in higher gene expression levels than needle injection. Electroporation enhanced gene expression for both intradermal delivery methods. Needle-free plasmid injection in combination with electroporation led to a more rapid induction of immune responses compared to other methods of plasmid administration. It was concluded that needle-free topical electroporation significantly enhances gene expression, possibly by improving cellular uptake of plasmid DNA.
PMID: 14664802 [PubMed - indexed for MEDLINE]
2003 Oct 25;315(2):345-52.
Needle-free Biojector injection of a dengue virus type 1 DNA vaccine with human immunostimulatory sequences and the GM-CSF gene increases immunogenicity and protection from virus challenge in Aotus monkeys.
Raviprakash K, Ewing D, Simmons M, Porter KR, Jones TR, Hayes CG, Stout R, Murphy GS.
Viral Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA. raviprakashk@nmrc.navy.mil
Abstract
A dengue-1 DNA vaccine containing sequences encoding premembrane and envelope proteins (DIME) was previously shown to elicit virus neutralizing antibodies in rhesus and Aotus monkeys, and the primates were partially protected from viremia upon challenge. To increase the neutralizing antibody levels and subsequent protection from virus challenge, four strategies were evaluated: (a) coimmunization with a plasmid expressing Aotus GM-CSF gene; (b) coimmunization with a plasmid containing human immunostimulatory sequences (ISS); (c) coimmunization with both the GM-CSF gene and ISS; and (d) delivery of vaccine using the needle-free Biojector system. Vaccination with the mixed formulation containing DIME, GM-CSF gene, and ISS, by either needle injection or Biojector, led to neutralizing antibody titers that were stable for up to 6 months after vaccination. Furthermore, 6 of 7 monkeys (85%), and 7 of 8 monkeys (87%) receiving this formulation were completely protected from viremia when challenged 1 and 6 months after vaccination, respectively. This is a significant improvement compared to our previous study in which one of three monkeys (33%) receiving just the DIME vaccine was completely protected from viremia at 6 months after immunization.
PMID: 14585337 [PubMed - indexed for MEDLINE]
2003 Nov;31(3):255-62.
Genetic immunization by jet injection of targeted pDNA-coated nanoparticles.
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 907 Rose Street, Lexington, KY 40536-0082, USA. rjmump2@uky.edu
Abstract
Genetic immunization strategies have largely focused on the use of "naked" plasmid DNA or the gene gun. However, there remains a clear need to further improve the efficiency and/or cost of potential DNA vaccines. The theoretical basis of our research is to rationally design genetic immunization methodologies for nanoparticle-based delivery systems of plasmid DNA, perhaps in combination with already commercially available needle-free devices, such as the Biojector 2000. These methodologies may both reduce the dose of pDNA required and enhance the breadth and depth of protective immune responses (i.e., humoral and cellular). The purpose of this article is to provide detailed experimental methods to (1) engineer and characterize pDNA-coated cationic nanoparticles (<100nm) directly from oil-in-water microemulsion precursors and (2) enhance both the breadth and depth of immune responses after immunization of mice with pDNA-coated nanoparticles by different routes of administration, including intradermal, using a needle-free jet injection device.
PMID: 14511958 [PubMed - indexed for MEDLINE]
2003 Feb;10(3):251-60.
Enabling topical immunization via microporation: a novel method for pain-free and needle-free delivery of adenovirus-based vaccines.
Bramson J, Dayball K, Evelegh C, Wan YH, Page D, Smith A.
Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Room HSC-4H21B, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Abstract
The skin represents an excellent site for vaccine inoculation due to its natural role as a first line of contact with foreign pathogens and the high local frequency of antigen presenting cells. To facilitate skin-directed immunization, a new technique has been developed (termed microporation) whereby a vaporization process is used to remove tiny areas of the stratum corneum creating microscopic pores that allow access to the underlying viable epidermis. Reporter gene expression was 100-fold increased following application of an adenovirus vector to microporated skin when compared to intact skin. Furthermore, 10-100-fold greater cellular and humoral immune responses were observed following topical administration of an adenovirus vaccine to microporated skin versus intact skin. Hairless mice responded to the microporated adenovirus vaccine equivalently to mice with normal hair follicle distribution demonstrating the activity of the microporated vaccine was not related to follicle count. In a tumor challenge model using a surrogate antigen, microporation increased vaccine efficacy by approximately 100-fold compared to intact skin. Finally, microporation enabled delivery of an adenovirus vaccine carrying a relevant melanoma antigen resulting in the development of auto-immune vitiligo and tumor protection. Thus, the microporation technology has proven to be a reliable and easy method to enable skin-directed vaccination.
PMID: 12571633 [PubMed - indexed for MEDLINE]
2003 Jan;96(1):215-9, table of contents.
A needle-free jet-injection system with lidocaine for peripheral intravenous cannula insertion: a randomized controlled trial with cost-effectiveness analysis.
Lysakowski C, Dumont L, Tramèr MR, Tassonyi E.
Division of Anesthesiology, Department of APSIC (Anesthesiology, Pharmacology, and Surgical Intensive Care), Geneva University Hospitals, Switzerland. lysakowski.christopher@hcuge.ch
Comment in:
Abstract
Insertion of a peripheral IV cannula is a common, although painful, procedure. We tested the analgesic efficacy, adverse effects, and cost-effectiveness of a needle-free intradermal drug delivery system (Jet) with lidocaine for the insertion of an IV cannula (18-gauge; dorsum of hand). Four-hundred patients were randomly allocated to one of four groups: (a) no treatment, (b) Jet (J-Tip), National Medical Products Inc, CA; $3.0 per device) with 0.5 mL of saline, (3) Jet with 0.5 mL of lidocaine 1%, and (4) Jet with 0.5 mL of lidocaine 2%. Pain was evaluated using a numerical verbal scale (NVS 0-10). A NVS < or =3 was considered as acceptable in this context. Incremental cost-effectiveness ratios were calculated. Without treatment, 42.4% of patients had a NVS < or = 3, 39.3% with saline, 60.7% with 1% lidocaine (relative risk [RR] compared with no treatment, 0.70; 95% confidence interval [CI], 0.53-0.93), and 86.7% with 2% lidocaine (RR, 0.49; 95% CI, 0.38-0.62). Nineteen and one-half percent of patients had a NVS >3 because of Jet treatment, 13.5% had local hyperemia, and 16.9% had minor local bleeding. Of all Jet treatments, 10.5% were technical failures, and there were 17.6% cannula insertion failures (10.1% without treatment [RR, 1.74; 95% CI, 0.92-3.32]). Compared with no treatment, costs to generate one additional patient with a NVS < or =3 were $23 with lidocaine 1% and $10 with lidocaine 2%. On insertion of an IV cannula on the back of the hand, 58% of patients report at least moderate pain. Lidocaine-Jet is analgesic; there is dose-responsiveness. However, Jet treatment is not painless, and costs incurred to achieve one success compared with doing nothing are not negligible. IMPLICATIONS: Insertion of an IV cannula is painful. Four-hundred patients were randomly allocated to test the analgesic efficacy, adverse effects, and cost-effectiveness of the needle-free intradermal drug delivery system (J-Tip); Jet). Jet with lidocaine is effective, but its application is not painless. Costs to achieve one patient with no more than moderate pain (numerical verbal scale < or =3 of 10) on insertion of an IV cannula are $10.
PMID: 12505955 [PubMed - indexed for MEDLINE]
2002 Nov;42(11):1262-8.
Pharmacokinetics and pharmacodynamics of a new formulation of recombinant human growth hormone administered by ZomaJet 2 Vision, a new needle-free device, compared to subcutaneous administration using a conventional syringe.
Agersø H, Møller-Pedersen J, Cappi S, Thomann P, Jesussek B, Senderovitz T.
Department of Clinical Pharmacology and Kinetics, Ferring Pharmaceuticals A/S, Copenhagen, Denmark.
Abstract
The objective of the present study was to investigate the applicability of a new human growth hormone (Zomacton) formulation, administered both by a conventional syringe and by a new needle-free device (ZomaJet 2 Vision). The study was performed according to a randomized, controlled, three-period crossover design. On 3 separate days, all subjects received in a random order a single subcutaneous injection of 1.67 mg hGH as follows: Zomacton 4 mg/ml conventional syringe administration (Treatment A), Zomacton 10 mg/ml conventional syringe administration (Treatment B), or Zomacton 10 mg/ml ZomaJet 2 Vision administration (Treatment C). The pharmacokinetic parameters were assessed for the individual subjects in each group by noncompartmental methods. Bioequivalence was assessed based on log-transformed AUC and C(max) values. To investigate the effectiveness of two formulations and the different administration methods, the pharmacodynamic parameters (insulin-like growth factor-1 [IGF-1] and free fatty acids [FFA]) were also evaluated. No subjects were withdrawn due to adverse events. The local tolerance assessment (assessed by inspection)revealed no differences between ZomaJet2 Vision application and conventional injections by syringe. Administration of the new hGH formulation by syringe was found to be bioequivalent with the reference treatment, both based on AUC and C(max) values; the new formulation administered by use of ZomaJet 2 Vision was found to be bioequivalent based on AUC values only. When using the ZomaJet 2 Vision, the absorption of hGH was faster, resulting in higher C(max) values. The maximum hGH serum concentration of around 20 ng/ml was observed 3.5 to 4 hours after drug administration. The terminal half-life was found to be around 2.5 hours. Comparison of the pharmacodynamic profiles (both IGF-1 and FFA) demonstrated bioequieffectiveness. These results support the use of jet injectors as a viable alternative to the traditional injection pens.
PMID: 12412826 [PubMed - indexed for MEDLINE]
2002 Oct;1(3):265-76.
Needle-free epidermal powder immunization.
PowderJect Vaccines Inc., Madison, WI 53711, USA. dexiang_chen@powderject.com
Abstract
Due to the presence of a network of antigen-presenting cells and other cells with innate and adaptive immune functions, the skin is both a sensitive immune organ and a practical target site for vaccine administration. A handful of needle-free immunization technologies have emerged in recent years that aim to take advantage of these characteristics. Skin delivery technologies provide potentially safer alternatives to needle injection and promises increased efficacy in the prevention and/or therapy of infectious diseases, allergic disorders and cancer. In this review, we will cover advances in needle-free skin vaccination technologies and their potential applications to disease prevention and therapy. Emphasis will be placed on epidermal powder immunization and particle-mediated ('gene gun') DNA immunization, which use similar mechanical devices to deliver protein and DNA vaccines, respectively, into the viable epidermis.
PMID: 12901567 [PubMed - indexed for MEDLINE]
2002 Sep 1;13(13):1551-60.
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.
Epstein JE, Gorak EJ, Charoenvit Y, Wang R, Freydberg N, Osinowo O, Richie TL, Stoltz EL, Trespalacios F, Nerges J, Ng J, Fallarme-Majam V, Abot E, Goh L, Parker S, Kumar S, Hedstrom RC, Norman J, Stout R, Hoffman SL.
Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910, USA. epsteinj@nmrc.navy.mil
Abstract
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.
PMID: 12228010 [PubMed - indexed for MEDLINE]
2002;103(4-5):144-51.
Optimizing delivery of therapeutics: percutaneous technologies.
The Department of Gynecology and Obstetrics, Stanford University School of Medicine, California, USA. mhenzl@aol.com
Abstract
The purpose of this communications is to 1) demonstrate the potential of percutaneous drug-delivery on the example of female reproductive steroids, 2) point out the differences between transdermal and conventional drug dosing, and 3) outline new technologies and innovations that are looming on the horizon, specifically in the area of pain control. Transdermal delivery systems are of two basic types. The first ones employ principles of passive diffusion, and they are used for hormonal replacement therapy (HRT) and contraception. Patches for HRT, designed to release estradiol (E2) only, require a simultaneous dosing with oral progestogens. Patches employing both E2 and a progestogen release the combination either continuously or sequentially. In the latter method, estrogen-only patches are applied for 14 days, followed by a 14-day application of patches releasing both hormones. Both methods successfully cope with symptoms and signs of menopause, including bone loss. Contraceptive transdermal patches deliver ethinylestradiol in combination with the progestogen norelgestromin. This system provides high contraceptive protection with predictable withdrawal bleeding and without major adverse events and weight changes. Hormones delivered by the skin avoid first-pass liver metabolism. Other advantages include rapid onset and termination of action, self-administration, and attainment of therapeutic hormone levels with low daily doses. A disadvantage is the variable intra- and inter-individual percutaneous absorption. In some patients, patches can cause skin irritation. Active systems deliver therapeutics across intact skin non-invasively by means of an electric potential (electrotransport). A system consisting of tooth-like titanium microprojections that penetrate only the keratinized epidermis facilitates painless and needle-free transport of complex molecules to the capillaries of the dermis. Other devices use low frequency ultrasound. These systems enable precise dosage, delivery of large molecules, such as growth hormone and vaccines, and dosing of analgesics "on demand". Novel transdermal technologies are profoundly changing the current methods of pain management. (Fig. 6, Ref. 47.).
PMID: 12413201 [PubMed - indexed for MEDLINE]
2001 Dec;75(23):11474-82.
Protection against tetanus by needle-free inoculation of adenovirus-vectored nasal and epicutaneous vaccines.
Shi Z, Zeng M, Yang G, Siegel F, Cain LJ, van Kampen KR, Elmets CA, Tang DC.
Vaxin, Inc., USA.
Abstract
The effectiveness of vaccination programs would be enhanced greatly through the availability of vaccines that can be administered simply and, preferably, painlessly without the need for timed booster injections. Tetanus is a prime example of a disease that is readily preventable by vaccination but remains a major threat to public health due to the problems associated with administration of the present vaccine. Here we show that a protective immune response against live Clostridium tetani infection in mice can be elicited by an adenovirus vector encoding the tetanus toxin C fragment when administered as a nasal or epicutaneous vaccine. The results suggest that these vaccination modalities would be effective needle-free alternatives. This is the first demonstration that absorption of a small number of vectored vaccines into the skin following topical application of a patch can provide protection against live bacteria in a disease setting.
PMID: 11689629 [PubMed - indexed for MEDLINE]
2000 Sep;19(9):839-42.
Clinical immunogenicity of measles, mumps and rubella vaccine delivered by the Injex jet injector: comparison with standard syringe injection.
Sarno MJ, Blase E, Galindo N, Ramirez R, Schirmer CL, Trujillo-Juarez DF.
Vision Biotechnology Consulting, Escondido, CA, USA. mjsarno@aol.com
Abstract
BACKGROUND: The measles, mumps and rubella (MMR) vaccine confers trivalent immunity in >90% of subjects immunized. Alternatives to the use of needles for vaccine administration have recently been made available. We report the safety and efficacy of MMR vaccine delivered by a new needle-free jet injector (Injex) compared with needle syringe administration.
METHODS: Forty adolescent subjects were injected bilaterally via needle syringe and jet injector with MMR vaccine and reconstitution buffer. Subjects were blinded as to which device contained the vaccine. Subjects were followed longitudinally for 12 weeks postimmunization, and titers to measles, mumps and rubella immunogens were determined by enzyme immunoassays. Injection pain was quantified using the visual analog pain scale.
RESULTS: Adverse events were mild and included injection site soreness (jet injector, 2.5% of subjects; needle, 12.5%), injection site bleeding (jet injector, 0%; needle, 7.5%), malaise (jet injector, 0%; needle, 5%) and fever (jet injector, 0%; needle, 2.5%). All subjects displayed measles titers significantly above baseline during the follow-up. Ninety-five percent of subjects displayed titers above baseline for the mumps antigen vs. 97.5% for rubella. No significant differences in immunogenicity were found between groups receiving the vaccine via the jet injector or the needle syringe at any time during the follow-up (P > 0.05). Injection pain scores were not significantly different between injector types (P > 0.05).
CONCLUSIONS: We conclude that the measles, mumps and rubella vaccine can be safely and effectively delivered by the Injex jet injector. This device therefore provides an alternative to standard needle injection and a methodology that might reduce the risk of needle stick accidents.
PMID: 11001106 [PubMed - indexed for MEDLINE]
2000 Mar;55(3):247-50.
Evaluation of a needle-free injection system for local anaesthesia prior to venous cannulation.
Cooper JA, Bromley LM, Baranowski AP, Barker SG.
Royal Free and University College Medical School, Room 103, 1st Floor Crosspiece, Middlesex Hospital, Mortimer Street, London W1N 8AA, UK.
Comment in:
Abstract
We evaluated a single-use, disposable, carbon-dioxide-powered, needleless injector (J-Tip, National Medical Products Inc., CA, USA), which is claimed to deliver a virtually painless, subcutaneous injection. Seventy-two patients undergoing various types of surgery had a large-bore intravenous cannula inserted prior to induction of general anaesthesia. Three minutes beforehand, a subcutaneous injection of 0.3 ml of 1% plain lidocaine was administered. Subjects were randomly allocated to receive the lidocaine either by the needleless injector or from a conventional syringe and a 25 G needle. Pain scores were recorded on injection of the lidocaine and on insertion of the cannula. There was significantly less pain on injection with the needleless injector than with the 25 G needle (p < 0.001) but, surprisingly, there was more pain on cannulation (p < 0. 001). We conclude that the device certainly delivers a less painful subcutaneous injection than a 25 G needle, but perhaps provides less effective skin anaesthesia for venous cannulation at sites where the subcutaneous space is small; its use might be better suited to areas where the subcutaneous space is deeper.
PMID: 10671842 [PubMed - indexed for MEDLINE]
