Search Results (16)

Vaccines usually contain an adjuvant that activates innate immunity to promote the acquisition of adaptive immunity. Aluminum and lipid nanoparticles have been used for this purpose, but their accumulation or widespread circulation in the body can lead to adverse effects. In contrast, physical adjuvants, which use physical energy to transiently stress tissues, do not persist in exposed tissues or cause lasting adverse effects. Herein, we investigate the effects of intradermal injection of endotoxin-free ovalbumin (OVA) protein alone without additional adjuvants using a needle-free pyro-drive jet injector (PJI) on tumor vaccination efficacy. Intradermal injection of OVA protein alone using PJI significantly increased OVA-specific CD8⁺ T cell expansion in the lymph node, although lymph node swelling was much less than when aluminum hydroxide was used. The injection also induced OVA-specific killing activity and antibody production and showed strong CD8⁺ T cell-dependent prophylactic antitumor effects against transplanted E.G7-OVA tumors. In particular, intradermal injection of the fluorescent OVA protein significantly enhanced its uptake by XCR1⁺ dendritic cells, which have a strong ability to cross-present extracellular proteins in the skin and draining lymph nodes. In addition, the injection increased the expression of HMGB1, one of the potent danger signals whose expression has been reported to increase in response to shear stress. Thus, intradermal injection of OVA protein alone without any additional adjuvants using PJI induces potent CD8⁺ T cell-mediated antitumor immunity by enhancing its uptake into XCR1⁺ dendritic cells, which have a high cross-presentation capacity accompanied by an increased expression of shear stress-induced HMGB1. Full article

Background/Objectives: Porcine circovirus type 2 (PCV2) has a major impact on swine productivity. Vaccines are used to aid in control and mitigate production losses. We investigated the protection provided by an intradermal PCV2 vaccine against a field strain in Taiwan. Methods: We conducted a safety and efficacy study. In the safety study, four Specific Pathogen Free (SPF) piglets were enrolled in the study. One was selected as the control and left unvaccinated, one was selected to be intradermally vaccinated with five times the standard dose (1 mL, Porcilis^® PCV ID), and the other two were vaccinated with two times the standard dose (0.4 mL, Porcilis^® PCV ID). All animals were observed for 3 weeks for adverse events post-vaccination. In the efficacy study, twelve SPF pigs negative for the PCV2 antibody were randomly divided into two groups. The first group of six pigs was vaccinated (Porcilis PCV ID, 0.2 mL) intradermally at 3 weeks of age. The second group of six pigs was sham vaccinated with 0.2 mL of normal saline. At 7 weeks of age, all pigs were challenged with the PCV2 strain CYC08 (1 × 10⁵ TCID₅₀/mL) by nasal and intramuscular injection. Clinical monitoring of body temperature and mortality was conducted daily. At 11 weeks of age, all animals were sacrificed for histopathological analysis. Results: No adverse events were reported in the safety study. In the efficacy study, the vaccinated animals had statistically improved results in the following areas post-challenge: body temperature rise, viremia, virus shedding, mortality, tissue histopathological and microscopic scores. Conclusions: The study results support that a one-dose PCV2 vaccine administered intradermally with a needle-free injector is safe and provides protection when challenged with a field PCV2 strain. Full article

mRNA vaccines were successfully developed and approved for emergency use to fight coronavirus disease 2019. However, the effect of DNA vaccines against SARS-CoV-2 is considerably lower than that of mRNA vaccines. A pyro-drive jet injector (PJI) efficiently delivers plasmid DNA intradermally into animal models. Here, we compared the immunogenic potential of DNA and mRNA vaccines in mice using the same platform. PJI was used to deliver naked mRNA and pDNA and their efficacy in inducing antigen expression and immune responses was assessed. Our results showed that PJI efficiently delivered mRNA into the skin, and a smaller effective dose than that of pDNA injection was required to achieve similar levels of antigen expression. The PJI-delivered CpG-free pDNA vaccine efficiently induced antigen-specific antibody production and a cell-mediated IFN-γ response compared to the mRNA vaccine, as well as the upregulation of inflammatory cytokines (IL-6, IFN-γ, and IL-1β) in the skin and lymph nodes. However, the intradermal mRNA vaccine was significantly less immunogenic than the standard intramuscular mRNA-lipid nanoparticle vaccine, despite equivalent mRNA dosages. Improvements in lipid nanoparticle and mRNA technology have revolutionized mRNA vaccines, and DNA vaccines can be similarly modified for higher clinical efficacy. Full article

All pigs in the Republic of Korea are given the foot-and-mouth disease virus (FMDV) vaccine intramuscularly (IM) as part of the country’s vaccination policy. However, the IM administration of the FMDV vaccine to pig results in residual vaccine components in the muscle and undesirable changes in muscle and soft tissues, causing economic losses in swine production. In this study, we evaluated whether intradermal (ID) vaccination could be proposed as an alternative to IM administration. ID vaccination (0.2 mL on each side of the neck muscle) and IM vaccination (2 mL on each side of the neck muscle) were performed twice, separated by 14 days, using a commercial FMD vaccine in specific-pathogen-free pigs. We observed growth performance, gross and microscopic lesions at the inoculation site, FMDV-specific antibodies, and neutralizing antibodies for 35 days after vaccination. Side effects on the skin grossly appeared following ID administration, but most were reduced within two weeks. All ID-vaccinated pigs showed inflammatory lesions limited to the dermis, but IM-vaccinated pigs had abnormal undesirable changes and pus in the muscle. ID-vaccinated pigs performed comparably to IM-vaccinated pigs in terms of growth, FMD virus-specific antibodies, protection capability against FMDV, and T-cell induction. This study demonstrated that the ID inoculation of the inactivated FMD vaccine induced immune responses comparable to an IM injection at 1/10 of the inoculation dose and that the inoculation lesion was limited to the dermis, effectively protecting against the formation of abnormal undesirable changes in muscle and soft tissues. Full article

Acne scars, particularly atrophic ones, present a persistent challenge in cosmetic medicine and surgery, requiring extended and multifaceted treatment approaches. Poly-(lactic acid) injectable fillers show promise in managing atrophic acne scars by stimulating collagen synthesis. However, the utilization of needle-free injectors for delivering poly-(lactic acid) into scars remains an area requiring further exploration. In this article, a summary of the latest advancements in needle-free jet injectors is provided, specifically highlighting the variations in jet-producing mechanisms. This summary emphasizes the differences in how these mechanisms operate, offering insights into the evolving technology behind needle-free injection systems. The literature review revealed documented cases focusing on treating atrophic acne scars using intralesional poly-(lactic acid) injections. The results of these clinical studies could be supported by separate in vitro and animal studies, elucidating the feasible pathways through which this treatment operates. However, there is limited information on the use of needle-free jet injectors for the intradermal delivery of poly-(lactic acid). Clinical cases of atrophic acne scar treatment are presented to explore this novel treatment concept, the needle-free delivery of poly-(lactic acid) using a jet pressure-based injector. The treatment demonstrated efficacy with minimal adverse effects, suggesting its potential for scar treatment. The clinical efficacy was supported by histological evidence obtained from cadaver skin, demonstrating an even distribution of injected particles in all layers of the dermis. In conclusion, we suggest that novel needle-free injectors offer advantages in precision and reduce patient discomfort, contributing to scar improvement and skin rejuvenation. Further comprehensive studies are warranted to substantiate these findings and ascertain the efficacy of this approach in scar treatment on a larger scale. Full article

Intratumoural delivery of oncolytic viruses (OVs) to solid tumours is currently performed via multiple percutaneous methods of needle injections (NI). In this study, we investigated the potential use of a novel delivery approach, needle-free injection (NFI), to administer OVs to subcutaneous tumours. The stability and genetic integrity of several RNA and DNA viruses exposed to high-pressure jet injectors were first evaluated in vitro. We demonstrate that replication competence and infectivity of the viruses remained unchanged after NFI, as compared to traditional NI. Using the oncolytic Vesicular Stomatitis Virus expressing luciferase (VSVΔ51-Luc) in the syngeneic CT26 subcutaneous tumour model, we show that NFI administration not only successfully delivers infectious particles but also increases the dissemination of the virus within the tumour tissues when compared to NI. Furthermore, mice treated with VSVΔ51-Luc by NFI delivery showed similar reduction in tumour growth and survival compared to those with needle-administered virus. These results indicate that NFI represents a novel approach to administer and potentially increase the spread of OVs within accessible solid tumours, highlighting its usefulness in virotherapy. Full article

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. Full article

Serial femtosecond crystallography (SFX) using an X-ray free-electron laser (XFEL) can be applied to determine the room-temperature structure of target molecules while minimizing radiation damage and visualizing molecular dynamics. In SFX, a sample delivery system is required to deliver microcrystals to the XFEL beam path in a serial manner. We recently developed a sample delivery method, the combined inject-and-transfer system (BITS), which is a hybrid method based on the injector and fixed-target scanning approach. In this study, we introduced recently upgraded hardware to move the injection needle in the direction of the XYZ-axis and a graphic user interface for user motion control. Furthermore, we report that the viscous solution containing 10% (w/v) PEG 3350 or PEG 6000 that is widely used for protein crystallization can be stably deposited on polyimide film with a hydrophobic surface without any special treatment. Moreover, the development of an inject-and-diffuse method for time-resolved studies with liquid applications in the BITS and its preliminary results are reported. This study provides up-to-date instrument information to SFX users using BITS and provides insights to instrument developers for SFX. Full article

The current state of commercially available needle-free liquid jet injectors for drug delivery offers no way of controlling the output pressure of the device in real time, as the driving mechanism for these injectors provides a fixed delivery pressure profile. In order to improve the delivery efficiency as well as the precision of the targeted tissue depth, it is necessary to develop a power source that can accurately control the plunger velocity. The duration of a liquid jet injection can vary from 10 to 100 ms, and it generate acceleration greater than 2 g (where g is the gravity); thus, a platform for real-time control must exhibit a response time greater than 1 kHz and good accuracy. Improving the pioneering work by Taberner and others whereby a Lorentz force actuator based upon a voice coil is designed, this study presents a prototype injector system with greater controllability based on the use of a fully closed-loop control system and a classical three-phase linear motor consisting of three fixed coils and multiple permanent magnets. Apart from being capable of generating jets with a required stagnation pressure of 15–16 MPa for skin penetration and liquid injection, as well as reproducing typical injection dynamics using commercially available injectors, the novelty of this proposed platform is that it is proven to be capable of shaping the real-time jet injection pressure profile, including pulsed injection, so that it can later be tailored for more efficient drug delivery. Full article

Needle-free liquid jet injectors are medical devices used to administer pharmaceutical solutions through the skin. Jet injectors generate a high-speed stream of liquid medication that can puncture the skin and deliver the drug to the underlying tissues. In this work, we investigated the feasibility of using liquid jet injectors to administer nanosuspensions, assessing the impact of the jet injection on their pharmaceutical and physicochemical properties. For this purpose, the model drug diclofenac was used to prepare a set of nanosuspensions, stabilized by poloxamer 188, and equilibrated at different pHs. The hydrodynamic diameter and morphology of the nanocrystals were analyzed before and after the jet injection across porcine skin in vitro, together with the solubility and release kinetics of diclofenac in a simulated subcutaneous environment. The efficacy of the jet injection (i.e., the amount of drug delivered across the skin) was evaluated for the nanosuspension and for a solution, which was used as a control. Finally, the nanosuspension was administered to rats by jet injector, and the plasma profile of diclofenac was evaluated and compared to the one obtained by jet injecting a solution with an equal concentration. The nanosuspension features were maintained after the jet injection in vitro, suggesting that no structural changes occur upon high-speed impact with the skin. Accordingly, in vivo studies demonstrated the feasibility of jet injecting a nanosuspension, reaching relevant plasma concentration of the drug. Overall, needle-free jet injectors proved to be a suitable alternative to conventional syringes for the administration of nanosuspensions. Full article

The objective of this study was to assess the clinical, immunological, microbiological, and pathological evaluation of trivalent vaccine containing porcine circovirus types 2a/b (PCV2a/b) and Mycoplasma hyopneumoniae given by two different needle-free injection devices compared with conventional needle-syringe injection in a herd with subclinical PCV2d infection and enzootic pneumonia. A total of 240 21-day-old pigs, which weighed between 5 to 6 kg, were randomly divided into four groups (60 pigs per group, 30 = male and 30 = female per group). Injection site reactions in the pigs were minimal for the two needle-free injection devices and needle-syringe injection. Trivalent vaccination of pigs with two needle-free injection devices was not inferior to conventional needle-syringe injection for growth performance. Trivalent vaccination of pigs with two different needle-free injection devices reduced levels of PCV2d loads in serum and M. hyopneumoniae loads in the larynx equally compared to the conventional needle-syringe injection. The amount of PCV2d load in serum from the needle-free Pulse FX injection device at 49 days post vaccination showed non-inferiority to conventional needle-syringe injection. The immune response against PCV2 and M. hyopneumoniae to trivalent vaccine given with the needle-free Pulse FX injection device was non-inferior to conventional needle-syringe injection. The pigs from the two needle-free injection device and conventional needle-syringe injection had significantly (p < 0.05) lower macroscopic and microscopic lung lesion scores, and microscopic lymphoid lesions than from unvaccinated. The results of this study demonstrated that vaccination of trivalent vaccine by the two needle-free Pulse injection devices used in the study was non-inferior to that by conventional needle-syringe injection for growth performance, immune response against PCV2 and M. hyopneumoniae, and reduction of PCV2 viremia. Full article

Swift vaccination is necessary as a response to disease outbreaks and pandemics; otherwise, the species under attack is at risk of a high fatality rate or even mass extinction. Statistics suggest that at least 16 billion injections are administered worldwide every year. Such a high rate of needle/syringe injection administration worldwide is alarming due to the risk of needle-stick injuries, disease spread due to cross-contamination and the reuse of needles, and the misuse of needles. In addition, there are production, handling, and disposal costs. Needle phobia is an additional issue faced by many recipients of injections with needles. In addition to a detailed literature review highlighting the need for needle-free injection systems, a compressed air-driven needle-free jet injection system with a hydro-pneumatic mechanism was designed and developed by employing an axiomatic design approach. The proposed injection system has higher flexibility, uninterrupted force generation, and provides the possibility of delivering repeated injections at different tissue depths from the dermis to the muscle (depending on the drug delivery requirements) by controlling the inlet compressed air pressure. The designed needle-free jet injector consists of two primary circuits: the pneumatic and the hydraulic circuit. The pneumatic circuit is responsible for driving, pressurizing, and repeatability. The hydraulic circuit precisely injects and contains the liquid jet, allowing us to control the volume of the liquid jet at elevated pressure by offering flexibility in the dose volume per injection. Finally, in this paper we report on the successful design and working model of an air-driven needle-free jet injector for 0.2–0.5 mL drug delivery by ex vivo experimental validation. Full article

We noted recently that the injection of cells with a needle through a cystoscope in the urethral sphincter muscle of pigs failed to deposit them nearby or at the intended target position in about 50% of all animals investigated (n > 100). Increasing the chance for precise cell injection by shotgun approaches employing several circumferential injections into the sphincter muscle bears the risk of tissue injury. In this study, we developed and tested a novel needle-free technique to precisely inject cells in the urethral sphincter tissue, or other tissues, using a water-jet system. This system was designed to fit in the working channels of endoscopes and cystoscopes, allowing a wide range of minimally invasive applications. We analyze key features, including the physical parameters of the injector design, pressure ranges applicable for tissue penetration and cell injections and biochemical parameters, such as different compositions of injection media. Our results present settings that enable the high viability of cells post-injection. Lastly, the method is suitable to inject cells in the superficial tissue layer and in deeper layers, required when the submucosa or the sphincter muscle of the urethra is targeted. Full article

Serial crystallography (SX) using X-ray free electron laser or synchrotron X-ray allows for the determination of structures, at room temperature, with reduced radiation damage. Moreover, it allows for the study of structural dynamics of macromolecules using a time-resolved pump-probe, as well as mix-and-inject experiments. Delivering a crystal sample using a viscous medium decreases sample consumption by lowering the flow rate while being extruded from the injector or syringe as compared to a liquid jet injector. Since the environment of crystal samples varies, continuous development of the delivery medium is important for extended SX applications. Herein, I report the preparation and characterization of a lard-based sample delivery medium for SX. This material was obtained using heat treatment, and then the soluble impurities were removed through phase separation. The lard injection medium was highly stable and could be injected via a syringe needle extruded at room temperature with a flow rate < 200 nL/min. Serial millisecond crystallography experiments were performed using lard, and the room temperature structures of lysozyme and glucose isomerase embedded in lard at 1.75 and 1.80 Å, respectively, were determined. The lard medium showed X-ray background scattering similar or relatively lower than shortenings and lipidic cubic phase; therefore, it can be used as sample delivery medium in SX experiments. Full article

The article concerns the possibility of using a fuel pretreatment system in modern compression ignition CI engines, the main task of which is the reduction of toxic emissions in the form of exhaust gases. This fuel pretreatment system consists of a catalytic reactor used in common rail (CR), and a modified fuel atomizer into spiral‒elliptical channels covered with catalytic material. In the system presented here, platinum was the catalyst. The catalyst’s task is to cause the dehydrogenation reaction of paraffin hydrocarbons contained in the fuel to create an olefin form, with the release of a free hydrogen molecule. In the literature, the methods of using catalysts in the exhaust systems of engines, or in combustion chambers, injection pumps, or fuel injectors, are known. However, the use of a catalytic reactor in the CR system in a high-pressure fuel atomizer rail is an innovative project proposed by the authors. Conditions in the high-pressure CR system are favorable for the catalyst’s operation. In addition, the spiral‒elliptical channels made on the inoperative part of the fuel atomizer needle increase the flow turbulence and contact surface for the catalyst. Full article