Needle-free Injection System Research Articles

Evaluation of a needle-free injection system for administration of cloprostenol for luteolysis in lactating dairy cows

Luteolytic drugs are critical for managing reproductive success in dairy cows. Currently prostaglandin analogs are only ap­proved for intramuscular injection. The utilization of a needle and syringe for administration of any drug can result in needle-stick injuries to workers. Furthermore, needle-free injection systems have been shown to eliminate transmission of blood­borne pathogens, such as anaplasmosis, in cattle. Data on the efficacy of needle-free injection systems and their application in an estrous synchronization protocol has not been reported. The objective of the present study was to evaluate the effective­ness of utilizing a needle-free injection system (Pulse Needle­Free Systems, Lenexa, KS) for the intramuscular delivery of clo­prostenol (Estrumate®, Merck Animal Health, Madison, NJ) for the purpose of estrous synchronization in lactating dairy cows.

Impact of ion-specific interactions on laser-induced liquid microjet generation

Jet velocity and jet power are the crucial parameters that govern the release profile of drugs/vaccines in needle-free injection systems, where salts are considered as one of the essential constituents of drugs/vaccines as adjuvants. However, the impact of salts on the generation of laser-induced liquid microjets that have shown tremendous potential for drug delivery has remained unexplored. Here, we have investigated the influence of Hofmeister ions on the velocity of laser-induced liquid jets in rhodamine 6G (Rh6G) dye solution. A comprehensive experimental approach is adopted to find out the values of the liquid microjet velocity by varying the parameters, such as input energy of the laser beam, concentrations of the dye, and specific Hofmeister ions in the aqueous solution. From our experimental findings, it is observed that the presence of ions significantly influences the jet velocity that follows the Hofmeister series: SO42−>I−>SCN−. This, in turn, governs the ion-specific penetration depth of liquid jets as simulated for the model soft tissues. The observed Hofmeister trend in the jet velocity values showcases the possible specific-ion interactions between anions and Rh6G molecules in the aqueous solution. Our detailed experimental findings on ion-specific jet velocity and jet power could be beneficial in designing needle-free drug delivery systems with controlled penetration depths.

Needle-Free Jet Injection of Poly-(Lactic Acid) for Atrophic Acne Scars: Literature Review and Report of Clinical Cases.

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.

Evaluation of luciferase and prefusion-stabilized F protein from respiratory syncytial virus mRNA/LNPs in pre-clinical models using jet delivery compared to needle and syringe

Described here is the evaluation of a luciferase (luc) and respiratory syncytial virus (RSV) messenger RNA / lipid nanoparticle (mRNA/LNP) vaccine using a Needle-free Injection System, Tropis®, from PharmaJet® (Golden, Colorado USA). Needle-free jet delivery offers an alternative to needle/syringe. To perform this assessment, compatibility studies with Tropis were first performed with a luc mRNA/LNP and compared to needle/syringe. Although minor changes in particle size and encapsulation efficiency were observed when using Tropis on the benchtop, in vitro luciferase activity remained the same. Next, the luc mRNA/LNP was administered to rats intramuscularly using Tropis or needle/syringe and tracking of the injection and distribution was performed. Lastly, an mRNA encoding a prefusion-stabilized F protein from RSV was delivered intramuscularly using both Tropis and needle/syringe at 1 and 5 mcg mRNA. An equivalent IgG response was observed using both Tropis and needle/syringe. The cell mediated immune (CMI) response was also evaluated, and responses to RSV-F were detected from animals immunized with needle/syringe at all dose levels, and from the animals immunized with Tropis in the 5 and 25 ug groups. These results indicated that delivery of mRNA/LNPs with Tropis is a potential means of administration and an alternative to needle/syringe.

A novel use of a needle-free injection system for improved nucleic acid delivery and expression in vivo.

Transfection, a nonviral method of nucleic acid delivery, often exhibits poor efficiency in vivo. The needle-based in vivo delivery of transfection reagents can be invasive. Here, we report a noninvasive protocol for in vivo gene delivery via the needle-free MED-JET H4 MULTIJET (MJH4M) device using both "home-made" glucose-based and commercial transfection reagents. The objective of this study was to compare the relative transfection efficiencies of the needle-free system to that of the needle-based delivery method. We observed a 15-fold increase in transfection efficiency using the needle-free MJH4M device when compared to the needle-based delivery method. The highest transfection efficiency was achieved using a 5% glucose solution as the delivery vehicle.

Dynamic interaction of injected liquid jet with skin layer interfaces revealed by microsecond imaging of optically cleared ex vivo skin tissue model

BackgroundNeedle-free jet injection (NFJI) systems enable a controlled and targeted delivery of drugs into skin tissue. However, a scarce understanding of their underlying mechanisms has been a major deterrent to the development of an efficient system. Primarily, the lack of a suitable visualization technique that could capture the dynamics of the injected fluid–tissue interaction with a microsecond range temporal resolution has emerged as a main limitation. A conventional needle-free injection system may inject the fluids within a few milliseconds and may need a temporal resolution in the microsecond range for obtaining the required images. However, the presently available imaging techniques for skin tissue visualization fail to achieve these required spatial and temporal resolutions. Previous studies on injected fluid–tissue interaction dynamics were conducted using in vitro media with a stiffness similar to that of skin tissue. However, these media are poor substitutes for real skin tissue, and the need for an imaging technique having ex vivo or in vivo imaging capability has been echoed in the previous reports.MethodsA near-infrared imaging technique that utilizes the optical absorption and fluorescence emission of indocyanine green dye, coupled with a tissue clearing technique, was developed for visualizing a NFJI in an ex vivo porcine skin tissue.ResultsThe optimal imaging conditions obtained by considering the optical properties of the developed system and mechanical properties of the cleared ex vivo samples are presented. Crucial information on the dynamic interaction of the injected liquid jet with the ex vivo skin tissue layers and their interfaces could be obtained.ConclusionsThe reported technique can be instrumental for understanding the injection mechanism and for the development of an efficient transdermal NFJI system as well.

Improved DNA Vaccine Delivery with Needle-Free Injection Systems.

DNA vaccines have inherent advantages compared to other vaccine types, including safety, rapid design and construction, ease and speed to manufacture, and thermostability. However, a major drawback of candidate DNA vaccines delivered by needle and syringe is the poor immunogenicity associated with inefficient cellular uptake of the DNA. This uptake is essential because the target vaccine antigen is produced within cells and then presented to the immune system. Multiple techniques have been employed to boost the immunogenicity and protective efficacy of DNA vaccines, including physical delivery methods, molecular and traditional adjuvants, and genetic sequence enhancements. Needle-free injection systems (NFIS) are an attractive alternative due to the induction of potent immunogenicity, enhanced protective efficacy, and elimination of needles. These advantages led to a milestone achievement in the field with the approval for Restricted Use in Emergency Situation of a DNA vaccine against COVID-19, delivered exclusively with NFIS. In this review, we discuss physical delivery methods for DNA vaccines with an emphasis on commercially available NFIS and their resulting safety, immunogenic effectiveness, and protective efficacy. As is discussed, prophylactic DNA vaccines delivered by NFIS tend to induce non-inferior immunogenicity to electroporation and enhanced responses compared to needle and syringe.

Needle-free injection system delivery of ZyCoV-D DNA vaccine demonstrated improved immunogenicity and protective efficacy in rhesus macaques against SARS-CoV-2.

The apprehension of needles related to injection site pain, risk of transmitting bloodborne pathogens, and effective mass immunization have led to the development of a needle-free injection system (NFIS). Here, we evaluated the efficacy of the NFIS and needle injection system (NIS) for the delivery and immunogenicity of DNA vaccine candidate ZyCoV-D in rhesus macaques against SARS-CoV-2 infection. Briefly, 20 rhesus macaques were divided into 5 groups (4 animals each), that is, I (1 mg dose by NIS), II (2 mg dose by NIS), III (1 mg dose by NFIS), IV (2 mg dose by NFIS) and V (phosphate-buffer saline [PBS]). The macaques were immunized with the vaccine candidates/PBS intradermally on Days 0, 28, and 56. Subsequently, the animals were challenged with live SARS-CoV-2 after 15 weeks of the first immunization. Blood, nasal swab, throat swab, and bronchoalveolar lavage fluid specimens were collected on 0, 1, 3, 5, and 7 days post infection from each animal to determine immune response and viral clearance. Amongall the five groups, 2 mg dose by NFIS elicited significant titers of IgG and neutralizing antibody after immunization with enhancement in their titers postvirus challenge. Besides this, it also induced increased lymphocyte proliferation and cytokine response. The minimal viral load post-SARS-CoV-2 challenge and significant immune response in the immunized animals demonstrated the efficiency of NFIS in delivering 2 mg ZyCoV-D vaccine candidate.

Effect of the new needle-free injection system on pain perception and dental anxiety during anesthesia: randomized controlled split-mouth study.

Pain management is one of the most important factors affecting the success of pediatric dentistry. Therefore, new needle- and pain-free local anesthesia techniques have been developed in parallel with technological advancements. The purpose of this study is to compare the pain perception and dental anxiety levels associated with a needle-free injection system (Comfort-in™) and the classic needle method during treatment-required infiltration anesthesia in children. This randomized controlled crossover split-mouth clinical study included 94 children who required dental treatment with local anesthesia using a dental needle or needle-free injection system for the bilateral primary molars. The Wong-Baker Scale (WBS) was used to measure pain perception at different times, and the Modified Child Dental Anxiety Scale (MCDAS) was used to measure the anxiety level of the child. A statistical software package was used to process the data. Statistical significance was set at P < 0.05. There was no significant difference between the needle-free injection system and dental needle method during the induction stage for filling and pulpotomy (P > 0.05). "Pain on postoperative 1st day" was similar in both types of anesthesia (P = 0.750). The needle-free injection system was as effective as the dental needle method. The Comfort-in™ system was an acceptable alternative for patients during the postoperative period. Understanding how pain management may be provided during local anesthesia administration and a child's fear and anxiety regarding the dentist may lead to better dental compliance.

Effect of a needle-free system versus traditional anesthesia on pain perception during palatal injections in children.

Needle-free injection systems can contribute to the prevention of needle-related pain during palatal infiltration anesthesia (PIA) in children. Research on this topic in children is required. The purpose of this clinical study was to evaluate the effectiveness and patient preference of a needle-free system versus traditional anesthesia (TA) on pain perception during PIA in children. The study was designed as a randomized, controlled crossover clinical study with 48 children aged 6-12 years requiring dental treatment with PIA in bilateral maxillary primary molars. TA was applied on one side and the Comfort-in™ injection system (CIS) on the other side in two separate sessions. Then, patient preference was recorded. The pain perception during PIA was evaluated using the Wong-Baker FACES Pain Rating Scale (PRS) and the Face, Legs, Activity, Cry, Consolability (FLACC) Scale. The data were analyzed for statistical significance (p < .05). There were statistically significant differences between the TA and the CIS according to the PRS and FLACC Scale scores. On both scales, significantly higher pain ratings were observed in the TA group during PIA (p < .001). There was a statistically significant difference in terms of patient preference (p < .001). Although 77.1% (n=37) of the children preferred the CIS, 22.9% (n=11) preferred the TA. Moreover, patient preference for the CIS was significantly higher in older children (p < .01). The application of a needle-free system during PIA ensured a decrease in pain perception in children.

Abstract 2052: LAMP1 targeting of the large T antigen of Merkel cell polyomavirus elicits potent CD4+ T cell responses, tumor inhibition, and provides rationale for first-in-human trial

Abstract The majority of Merkel cell carcinomas (MCC), a rare and highly aggressive type of neuroendocrine skin cancer, are associated with Merkel cell polyomavirus (MCPyV) infection. MCPyV integrates into the host genome, resulting in expression of a truncated form of the viral large T antigen (LT) in infected cells and thus making LT an attractive target for therapeutic cancer vaccines. We designed a cancer vaccine that promotes potent, antigen-specific CD4+ T cell responses to MCPγV-LT. To activate antigen-specific CD4+ T cells in vivo, we utilized our nucleic acid platform, UNITE࣪ (UNiversal Intracellular Targeted Expression), which fuses a tumor-associated antigen with lysosomal-associated membrane protein 1 (LAMP1). This lysosomal targeting technology results in enhanced antigen presentation and a balanced T cell response. LTS220A, encoding a mutated form of MCPγV-LT that diminishes its pro-oncogenic properties, was introduced into the UNITE࣪ platform. In pre-clinical studies, vaccination with LTS220A-UNITE࣪ (ITI-3000) induced antigen-specific CD4+ T cells that were sufficient to delay tumor growth, and this effect was dependent on their ability to produce IFNγ. Moreover, ITI-3000 induced a favorable tumor microenvironment (TME), including significantly enhanced numbers of CD4+ and CD8+ T cells as well as NK and NKT cells. These findings strongly suggest that in pre-clinical studies, DNA vaccination using the UNITE࣪ platform enhances CD4+ T cell responses to MCPγV-LT that result in significant anti-tumor immune responses. We are planning a first-in-human (FIH) Phase 1 open-label study to evaluate the safety, tolerability, and immunogenicity of ITI-3000 in patients with polyomavirus-positive MCC. Patients will receive up to four intramuscular vaccinations of 4mg of ITI-3000 using the PharmaJet Stratis® needle-free injection system. The primary objectives will be safety and tolerability, observing dose-limiting toxicities, serious adverse events, standard clinical assessments, and safety laboratory parameters. Immunogenicity of the vaccine will be measured by peripheral blood assessments of T cell activation using ELISpot and flow cytometry assays. Citation Format: Claire Buchta Rosean, Mohan Karkada, David M. Koelle, Paul Nghiem, Teri Heiland. LAMP1 targeting of the large T antigen of Merkel cell polyomavirus elicits potent CD4+ T cell responses, tumor inhibition, and provides rationale for first-in-human trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2052.

Dermal Microvascular Units in Domestic Pigs (Sus scrofa domestica): Role as Transdermal Passive Immune Channels.

The dermal microvascular unit (DMU) is a perivascular functional unit in the dermis. It is composed of microvascular and capillary lymphatics surrounded by immune cells. In this study, jet needle-free injection system was used to injected biocompatible carbon nanoparticles into the cervical skin of domestic pigs (Sus scrofa domestica) and assessed the morphological distribution of DMUs by hematoxylin erythrosine staining, immunohistochemistry (IHC), and transmission electron microscopy (TEM), and TEM was also used to observe the ultrastructural changes of DMUs after jet needle-free injection. Following our study, we identified DMUs in the dermis stratum papillare and similar structures in the dermis stratum reticulare, but the aggregation of CD68+ and CD1a+ cells in the dermis stratum papillare of DMUs by IHC confirmed that DMUs act as reservoirs of dermal immune cells, while similar structures in the dermis stratum reticulare should not be considered as DMUs. Ultrastructure of DMUs was revealed by TEM. Marvelous changes were found following xenobiotics attack, including the rearrangement of endothelial cells and pericytes, and the reactivity of immune cells. Novel interstitial cell telocyte (TC) was also identified around the microvasculature, which may have been previously known as the veil cell. Our results successfully identified the distribution of DMUs in the skin of domestic pigs, which might act as reservoirs of immune cells in the skin and play a role in immune surveillance and immune defense.

A DNA vaccine targeting VEE virus delivered by needle-free jet-injection protects macaques against aerosol challenge

We have previously shown that DNA vaccines expressing codon optimized alphavirus envelope glycoprotein genes protect both mice and nonhuman primates from viral challenge when delivered by particle-mediated epidermal delivery (PMED) or intramuscular (IM) electroporation (EP). Another technology with fewer logistical drawbacks is disposable syringe jet injection (DSJI) devices developed by PharmaJet, Inc. These needle-free jet injection systems are spring-powered and capable of delivering vaccines either IM or into the dermis (ID). Here, we evaluated the immunogenicity of our Venezuelan equine encephalitis virus (VEEV) DNA vaccine delivered by either the IM- or ID-DSJI devices in nonhuman primates. The protective efficacy was assessed following aerosol challenge. We found that a prime and single boost by either the IM or ID route resulted in humoral and cellular immune responses that provided significant protection against disease and viremia. Although the ID route utilized one-fifth the DNA dose used in the IM route of vaccination, and the measured humoral and cellular immune responses trended lower, the level of protection was high and performed as well as the IM route for several clinical endpoints.

DNA vaccines join the fight against COVID-19

DNA vaccines join the fight against COVID-19

Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India

BackgroundZyCoV-D, a DNA-based vaccine, showed promising safety and immunogenicity in a phase 1/2 trial. We now report the interim efficacy results of phase 3 clinical trial with ZyCoV-D vaccine in India.MethodsWe conducted an interim analysis of a multicentre, double-blind, randomised, placebo-controlled phase 3 trial at 49 centres in India. Healthy participants aged at least 12 years were enrolled and randomly assigned (1:1) to receive either ZyCov-D vaccine (Cadila Healthcare; 2 mg per dose) or placebo. An interactive web response system was used for randomisation (blocks of four) of participants as well as to enrol those aged 60 years and older with or without comorbid conditions, and those aged 12–17 years. It was also used to identify 600 participants for immunogenicity (blocks of six). Participants, investigators, and outcome assessors were masked to treatment assignment. Three doses of vaccine or placebo were administered intradermally via a needle-free injection system 28 days apart. The primary outcome was the number of participants with first occurrence of symptomatic RT-PCR-positive COVID-19 28 days after the third dose, until the targeted number of cases (interim analysis n=79, full analysis n=158) have been achieved. The analysis was done in the per-protocol population, which consisted of all participants with negative baseline SARS-CoV-2 status who received three doses of vaccine or placebo. Assessment of safety and tolerability was based on the safety population, which consisted of all enrolled participants who were known to have received at least one dose of study vaccine or placebo. This trial is registered with Clinical Trial Registry India, CTRI/2021/01/030416, and is ongoing.FindingsBetween Jan 16, and June 23, 2021 (data cutoff), 33 194 individuals were screened, of whom 5241 did not meet screening criteria and 27 703 were enrolled and randomly assigned to receive ZyCoV-D (n=13 851) or placebo (n=13 852). Per-protocol, 81 cases were eligible and included in efficacy analysis (20 of 12 350 in the ZyCoV-D group and 61 of 12 320 in placebo group). The ZyCoV-D vaccine efficacy was found to be 66·6% (95% CI 47·6–80·7). The occurrence of solicited adverse events was similar between the treatment groups (623 [4·49%] in the ZyCoV-D group vs 620 [4·47%] in the placebo group). There were two deaths (one in each group) reported at the data cutoff, neither of which was considered related to the study treatments.InterpretationIn this interim analysis, ZyCoV-D vaccine was found to be efficacious, safe, and immunogenic in a phase 3 trial.FundingNational Biopharma Mission, Department of Biotechnology, Government of India and Cadila Healthcare, Ahmedabad, Gujarat India.

Advances in Large Volume Subcutaneous Injections: A Pilot Tolerability Study of an Innovative Needle-Free Injection Platform.

Many medical conditions require chronic treatment with subcutaneous injectable biologics often exceeding 1.0 mL. However, subcutaneous administration of volumes of 2.0 mL or greater using a standard needle and syringe or auto-injector proves challenging, and patients often must administer two separate injections to achieve their full dose or endure injection times in excess of 10 s if using a mechanical autoinjector. In addition, needle-based injections often cause patient anxiety and discomfort. In this article, we describe an approach to meet these needs with a needle-free medication delivery device capable of rapidly delivering up to 2.0 mL with minimal discomfort. A pilot study was conducted with this needle-free injection system to evaluate the delivery of a 2.0 mL volume in human subjects. The results demonstrated that injections of up to 2.0 mL were well tolerated and often preferred over two separate 1.0 mL injections using the needle-free injection system.

A Needle-Free Jet Injection System for Controlled Release and Repeated Biopharmaceutical Delivery.

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.

Abstract CT021: INVAC-1, an optimized telomerase DNA vaccine in patients with advanced solid tumors: Final results of first-in-human phase I study

Abstract Background INVAC-1 is an optimized DNA plasmid encoding an inactive form of human Telomerase Reverse Transcriptase (hTERT), a universal tumor antigen expressed in most of human tumors with little or no expression in normal somatic cells. Primary pharmacodynamics, safety and toxicology studies showed that INVAC-1 was enzymatically inactive, immunogenically safe and well tolerated. In murine models, we demonstrated that INVAC-1 was able to induce hTERT specific cellular immune responses with CD4+ Th1 effector and memory CD8+ T-cells as well as slow tumor growth and increase survival rate by 50% in tumor-bearing mice. Methods We conducted a First-In-Human (FIH) study, 2-centre, Phase I, open label, 3+3 escalation design and multiple dose study examining the safety and tolerability of INVAC-1 administered at three dose levels (100, 400 and 800 µg) in 26 patients with relapsed or solid refractory tumors. INVAC-1 was administered either by intradermal (ID) injection followed by electroporation (EP) (n=20) or by Tropis® Needle Free Injection System (n=6). Results INVAC-1 vaccination was safe and well tolerated when administered ID (either with EP or by Tropis®) at the three tested doses. Only one treatment-related grade 3 SAE was reported. 58% of patients experienced disease stabilization up to 9.9 months. One-year survival was reached for 65% of patients. INVAC-1 elicited both hTERT specific Th1-dominant CD4 and cytotoxic CD8 T cell responses with no vaccine-induced peripheral immunosuppression. Anti-hTERT immune responses were enhanced by adding anti-PD-1 immune checkpoint inhibitor ex vivo. In addition, INVAC-1 vaccination was able to promote epitope spreading. Finally, correlation analysis between clinical and immunological data showed that patients with OS &amp;gt;1 year presented a significantly higher hTERT immune response after INVAC-1 vaccination compared to patients with OS &amp;lt;1 year. Moreover, estimated median OS in INVAC-1 immune responders was 17.4 months vs. 7 months for non-responders. Conclusion INVAC-1 vaccination was safe, well tolerated and immunogenic when administered ID at the three tested doses. Disease stabilization was observed for the majority of patients during the treatment period and beyond. Clinical trial identification #NCT02301754 Citation Format: Julie Garibal, Jacques Medioni, Luis Teixeira, Olivier Adotevi, Marie-Agnès Dragon-Durey, Caroline Laheurte, Claire Germain, Marie Escande, Maria Wehbe, Valérie Doppler, Thierry Huet, Pierre Langlade Demoyen. INVAC-1, an optimized telomerase DNA vaccine in patients with advanced solid tumors: Final results of first-in-human phase I study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT021.

Does the use of Dermojet affect the concentration of platelet‐rich plasma? An in vitro experimental investigation

Needle-free injection systems with high jet pressure have been used for seven decades for drug or vaccine administration via intradermal, subcutaneous, and intramuscular routes. These systems are used for the application of mesotherapy drugs in plastic surgery and dermatology. Platelet-rich plasma (PRP) tissue regeneration is applied intradermally by a needle for different indications, such as wound healing and scar revision. To prevent complaints such as pain, erythema, and ecchymosis by patients during this application, PRP was applied using Dermojet, a jet injector system with a spring-loaded system. In this study, after measuring the average platelet count in PRP preparations obtained from 18 volunteers, a 2.5cc PRP shot into an empty tube was performed with Dermojet. The mean platelet count was measured in a homogenized tube. The same procedures were performed for platelet-poor plasma (PPP). The platelet loss rates for PRP and PPP were compared. In addition, the amount of PRP in each shot of the Dermojet was calculated. When PRP and PPP were applied using the Dermojet, platelet loss was 8.41% and 8.33%, respectively. The difference in the number of platelets formed in PRP and PPP when applied with Dermojet was not statistically significant. PRP application with needle-free injection systems, such as Dermojet, may be an alternative because of patient comfort and the negligible platelet loss compared with the PRP application with the standard needle injection.

Impact of the mechanical properties of penetrated media on the injection characteristics of needle-free jet injection

Needle-free jet injection systems are characterized by the increased drug delivery efficacy over conventional needle-based injection systems and have become a viable alternative. The majority of previous studies have investigated underlying mechanisms of needle-free jet injection systems with an emphasis on the fluid dynamics of the propelled microjet without considering the influence of an injected medium on the penetration and dispersion of the microjet. Unlike the injected fluid introduced directly into a target region of the skin tissue through a hollow needle, the fluid microjet produced by a needle-free injector has to work through multiple skin tissue layers and interfaces having different mechanical properties. Here we evaluated injection characteristics in two hydrogel media having similar stiffness controlled precisely but different pore size and hence different fracture toughness. High-speed imaging data showed that the fracture toughness of the medium influenced the penetration mechanism of the injected microjet, whereas viscoelastic and poroelastic characteristics of the medium determined the final attainable injection profiles. The injection profiles were also dependent on the type and depth of the interface between the layers of two media, where tight and loose interfaces can have different effects on the distribution of injected drug as the injected fluid prefers the path having the least resistance. Our findings would improve the present understanding of needle-free jet injection systems and could help to develop more effective drug delivery systems.