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Intradermal injection of ovalbumin (OVA)‐expression plasmid DNA with the pyro‐drive jet injector (PJI), but not a needle syringe, efficiently increased OVA‐specific antibody production of both the IgG1 and IgG2a subclasses. (A) Mice that were intravenously injected with an equal number of OT‐I‐derived naive CD8⁺ T cells and OT‐II‐derived naive CD4⁺ T cells 1 day before were then intradermally injected twice at a 2‐week interval with OVA‐expression plasmid DNA using the PJI or a needle syringe, PBS, and OVA protein (500 μg) combined with complete Freund's adjuvant (CFA). At 1 week later, the titers of (B) anti‐OVA total IgG antibody, and the (C) IgG2a and (D) IgG1 isotype antibodies were measured in serum. Data shown are the mean ± SEM (n = 5) of three independent experiments. p‐values were determined using one‐way ANOVA with the Tukey test for multiple comparisons. *p < 0.05.
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The current success of mRNA vaccines against COVID-19 has highlighted the effectiveness of mRNA and DNA vaccinations. Recently, we demonstrated that a novel needle-free pyro-drive jet injector (PJI) effectively delivers plasmid DNA into the skin, resulting in protein expression higher than that achieved with a needle syringe. Here, we used ovalbumi...
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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. New technologies have been utilized to develop several types of vaccines to prevent the spread of SARS-CoV-2 infection, including mRNA vaccines. Our group previously developed an effective DNA-based vaccine. How...
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... At present, needle-free drug delivery technology is advancing towards high-capacity delivery, self-care, and gene therapy. Needle-free thermoresponsive jet injectors have been shown to effectively deliver plasmid DNA to the skin, resulting in higher protein expression compared to needle injectors [217]. Large-capacity subcutaneous needle-free syringes have an injection tolerance of up to 2.0 mL, and the injection effect is generally better than two separate 1.0 mL injections using a needle-free injection system [218]. ...
The escalating demand for enhanced therapeutic efficacy and reduced adverse effects in the pharmaceutical domain has catalyzed a new frontier of innovation and research in the field of pharmacy: novel drug delivery systems. These systems are designed to address the limitations of conventional drug administration, such as abbreviated half-life, inadequate targeting, low solubility, and bioavailability. As the disciplines of pharmacy, materials science, and biomedicine continue to advance and converge, the development of efficient and safe drug delivery systems, including biopharmaceutical formulations, has garnered significant attention both domestically and internationally. This article presents an overview of the latest advancements in drug delivery systems, categorized into four primary areas: carrier-based and coupling-based targeted drug delivery systems, intelligent drug delivery systems, and drug delivery devices, based on their main objectives and methodologies. Additionally, it critically analyzes the technological bottlenecks, current research challenges, and future trends in the application of novel drug delivery systems.
... Among them, a new needle-free pyro-drive jet injector, which has a unique characteristic utilizing gunpower as a mechanical driving force, provokes high jet velocity and consequently the wide dispersion of the injected DNA solution in the skin. A number of studies revealed that it is highly effective as a vaccinating tool to induce potent protective cellular and humoral immunity against infectious diseases and cancers [18]. To enhance immunogenicity, COVID-19 mRNA is encapsulated in LNPs, and the resultant mRNA-LNPs nanoparticles migrate systemically and are broadly distributed in the human body after intramuscular injection. ...
Cancer immunotherapy is a type of cancer therapy utilizing the immune system to fight against tumors [...]
... Herein, we used a novel needle-free, pyro-drive liquid jet injector (PYRO) (28) to deliver naked mRNA instantaneously and efficiently in the skin before considerable mRNA degradation. According to previous research, PYRO enhanced plasmid DNA (pDNA) delivery to rodent skin, providing efficient vaccination effects (29)(30)(31). Interestingly, in the present study, PYRO effectively (which was not certified by peer review) is the author/funder. ...
Naked mRNA-based vaccines may reduce the reactogenicity associated with delivery carriers, but their effectiveness has been suboptimal against infectious diseases. Herein, we aimed to enhance their efficacy by using a pyro-drive liquid jet injector that precisely controls pressure to widely disperse mRNA solution in the skin. The jet injection boosted naked mRNA delivery efficiency in the mouse skin. Mechanistic analyses indicate that dendritic cells, upon uptake of antigen mRNA in the skin, migrate to the draining lymph nodes for antigen presentation. Additionally, the jet injector activated innate immune responses in the skin, presumably by inducing physical stress, thus serving as a physical adjuvant. From a safety perspective, our approach, utilizing naked mRNA, restricted mRNA distribution solely to the injection site, preventing systemic pro-inflammatory reactions following vaccination. Ultimately, the jet injection of naked mRNA encoding SARS-CoV-2 spike protein elicited robust humoral and cellular immunity, providing protection against SARS-CoV-2 infection in mice. Furthermore, our approach induced plasma activity of neutralizing SARS-CoV-2 in non-human primates, comparable to that observed in mice, with no detectable systemic reactogenicity.
... Very recently, a novel needle-free PJI called Actranza TM lab (Daicel Corporation, Osaka, Japan) ( Figure 3) has been developed, which has a unique characteristic in that the PJI utilizes gunpower as a mechanical driving force, and in particular bi-phasic pyrotechnics to induce high jet velocity and the wide dispersion of the injected plasmid DNA solution into the skin and muscle of mice, rats, pigs and humans [42][43][44][45][46][47][48][49][50][51]. The pyrotechnic technology was previously developed and initially utilized in the inflator products in an airbag [52] (https://www.daicel.com/safety/en/inflator/, ...
... In a cancer experimental model, ovalbumin (OVA) was commonly used as an antigen, and the inoculation of C57BL/6 mice with tumor cells that were stably transfected with the OVA-expression vectors (lymphoma E.G7-OVA or melanoma B16F10-OVA) induced OVA-specific cellular and humoral immune responses. In a comparative study between the PJI and a needled syringe, the effectiveness of the induction of OVA-specific cellular and humoral immune responses by intradermal injection of OVA-expression plasmid (pOVA obtained from Addgene) was examined [50]. After a single intradermal injection of OVAexpression plasmid, OVA-specific cytotoxic CD8 + T cells (CTLs) were rapidly generated within 2 weeks, which was detected by a tetramer assay using flow cytometry. ...
... OVA-specific CD4 + T cells appeared to be more slowly activated, differentiating into both Th1 and Th2 cells. Consistent with the data, OVA-specific in vivo killing activity was induced, followed by OVA-specific antibody production, including both IgG2a and IgG1 isotypes [50]. The induction of the OVA-specific cellular immunity by the PJI was much higher than that by a needled syringe [50]. ...
Current worldwide mRNA vaccination against SARS-CoV-2 by intramuscular injection using a needled syringe has greatly protected numerous people from COVID-19. An intramuscular injection is generally well tolerated, safer and easier to perform on a large scale, whereas the skin has the benefit of the presence of numerous immune cells, such as professional antigen-presenting dendritic cells. Therefore, intradermal injection is considered superior to intramuscular injection for the induction of protective immunity, but more proficiency is required for the injection. To improve these issues, several different types of more versatile jet injectors have been developed to deliver DNAs, proteins or drugs by high jet velocity through the skin without a needle. Among them, a new needle-free pyro-drive jet injector has a unique characteristic that utilizes gunpower as a mechanical driving force, in particular, bi-phasic pyrotechnics to provoke high jet velocity and consequently the wide dispersion of the injected DNA solution in the skin. A significant amount of evidence has revealed that it is highly effective as a vaccinating tool to induce potent protective cellular and humoral immunity against cancers and infectious diseases. This is presumably explained by the fact that shear stress generated by the high jet velocity facilitates the uptake of DNA in the cells and, consequently, its protein expression. The shear stress also possibly elicits danger signals which, together with the plasmid DNA, subsequently induces the activation of innate immunity including dendritic cell maturation, leading to the establishment of adaptive immunity. This review summarizes the recent advances in needle-free jet injectors to augment the cellular and humoral immunity by intradermal injection and the possible mechanism of action.
