A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor α (VEGF-α) by a minor subset of activated EpCAM+CD59+Ly-6D+ cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guérin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.

Intravenous Bacillus Calmette-Guérin (BCG) Induces a More Potent Airway and Lung Immune Response than Intradermal BCG in Simian Immunodeficiency Virus-infected Macaques.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates M. tuberculosis infection outcomes in people living with HIV. Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. In this study, we investigated the immune responses elicited by BCG administered via i.v. or intradermal (i.d.) routes in SIV-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of M. tuberculosis challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic effectors, and key transcription factors. Our results showed that i.v. BCG induces a robust and sustained immune response, including tissue-resident memory T cells in lungs, polyfunctional CD4+ and CD8αß+ T cells expressing multiple cytokines, and CD8αß+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of i.v. BCG-vaccinated MCM. Although i.v. BCG vaccination resulted in an influx of tissue-resident memory T cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (>105 copies/ml) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on i.v. BCG-induced protection against M. tuberculosis.

Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine.

BACKGROUND: Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. METHODS: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. RESULTS: The median age of the participants was 38 years, and 60% were women; 78% were White and 22% Black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-ß receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. CONCLUSIONS: In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443.).

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation.

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP-to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation-to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

A Hollow Microneedle Equipped with a Micropillar for Improved Needle Insertion and Injection of Drug Solution.

PURPOSE: Hollow-type microneedles (hMNs) are a promising device for the effective administration of drugs into intradermal sites. Complete insertion of the needle into the skin and administration of the drug solution without leakage must be achieved to obtain bioavailability or a constant effect. In the present study, several types of hMN with or without a rounded blunt tip micropillar, which suppresses skin deformation, around a hollow needle, and the effect on successful needle insertion and administration of a drug solution was investigated. Six different types of hMNs with needle lengths of 1000, 1300, and 1500 µm with or without a micropillar were used. METHODS: Needle insertion and the disposition of a drug in rat skin were investigated. In addition, the displacement-force profile during application of hMNs was also investigated using a texture analyzer with an artificial membrane to examine needle factors affecting successful insertion and administration of a drug solution by comparing with in vivo results. RESULTS: According to the results with the drug distribution of iodine, hMN1300 with a micropillar was able to successfully inject drug solution into an intradermal site with a high success rate. In addition, the results of displacement-force profiles with an artificial membrane showed that a micropillar can be effective for depth control of the injected solution as well as the prevention of contact between the hMN pedestal and the deformed membrane. CONCLUSION: In the present study, hMN1300S showed effective solution delivery into an intradermal site. In particular, a micropillar can be effective for depth control of the injected solution as well as preventing contact between the hMN pedestal and the deformed membrane. The obtained results will help in the design and development of hMNs that ensure successful injection of an administered drug.

Mpox vaccination routes: prevalence, correlates and adverse effects of subcutaneous versus intradermal vaccination at a mass vaccination clinic in Sydney, Australia.

The Royal Prince Alfred Hospital Mpox Vaccination Clinic opened in response to the 2022 multicountry mpox outbreak. A total of 9500 vaccinations were administered intradermally and subcutaneously during the first 16 weeks of clinic operation. The rate of adverse events was 0.1%. Compared to people who received the vaccine intradermally, those who received it subcutaneously were more likely to be aged 30-39 years (P = 0.047), sexual partners of gay and bisexual men (P < 0.001), eligible for Medicare (P < 0.001) and born in the Philippines (P = 0.01) or Malaysia (P = 0.04).

Facial Skin Rejuvenation Using Poly- dl -Lactic Acid Injected With a Laser-Generated Needle-Free Microjet Injector.

BACKGROUND: A laser-induced needle-free microjet injector was developed for rapid, high-speed drug delivery of microliters into the skin. OBJECTIVE: This study evaluated the clinical rejuvenation effect of repeated dermal injections of the collagen simulator poly- dl -lactic acid (PDLA) using a laser-induced needle-free microjet injector. METHODS: Five PDLA injection sessions using a laser-induced needle-free microjet injector were conducted in patients concerned about aging skin. Facial uplifting, darkness, redness, roughness, pore size, subjective satisfaction, and side effects were evaluated before each session and 4 weeks after treatment completion. Histological evaluation was also performed with immunohistochemical staining of collagen and elastic fibers. RESULTS: The clinical results of 27 female patients were evaluated. The treatment resulted in a noticeable skin surface uplifting (0.711 ± 0.42 mm) and significant improvements in darkness ( p = .013), redness ( p = .009), and roughness ( p = .036), with no significant difference in the pore size ( p = .770). Patients were reported being satisfied with the overall therapeutic effects, despite mild and tolerable adverse effects. Histological findings revealed growth and thickening of collagen and elastic fibers, with marked increase in collagen I and III levels. CONCLUSION: Repeated dermal injections of PDLA using a laser-induced microjet injector offer excellent drug delivery, achieving high efficacy in skin rejuvenation, patient satisfaction, and safety.

Injectable platelet-rich fibrin for treatment of female pattern hair loss.

This case series evaluated use of injectable platelet rich fibrin (termed i-PRF+) for the treatment of female pattern hair loss (FPHL). Eleven individuals underwent 3-monthly intradermal injections of i-PRF+ using a mesotherapy gun. The mean number of hair follicles containing hairs per unit area improved at 3- and 6-months follow-up (p < .001), and all participants had a negative hair pull test. Hair volume and thickness, and patient-reported outcome scores also improved at follow-up (p < .001). Adverse effects were minor and self-limited. A series of three i-PRF+ injection sessions were effective for the treatment of FPHL, as shown by improved hair analysis parameters and patient self-assessment scores.

Management of primary plantar hyperhidrosis with botulinum toxin type A: A retrospective case series of 129 patients.

BACKGROUND/OBJECTIVES: To date, scientific data on the efficacy of botulinum toxin type A (BoNT-A) for primary plantar hyperhidrosis (PPH) are mainly derived from case reports and small case series. Herein, we sought to assess the efficacy and safety of BoNT-A for PPH on a large series of patients. METHODS: Medical records of patients who were referred to the outpatient department for hyperhidrosis of a tertiary care hospital and received BoNT-A for PPH from March 2003 until December 2022 were reviewed. RESULTS: A total of 129 patients [12 males, 117 females; median age 32 years (range, 16-72)] were included in the study, after excluding 24 patients with insufficient documented follow-up data. Most patients [115 (89.1%)] received onabotulinumtoxin-A, nine (7.0%) abobotulinumtoxin-A and five (3.9%) both in subsequent sessions. The mean number of sessions was 2.02 [standard deviation (SD), 2.29] and the mean duration of response 6.16 months (SD, 4.01). The percentage of response, as evaluated by Minor's test, was 71.67%, 63.44%, 47.78% and 34.13% after 1, 3, 6 and 9 months, respectively. Most patients were satisfied (21.7%) or very satisfied (58.9%) with the treatment. No serious side effects were reported. CONCLUSIONS: The results of this retrospective study suggest that BoNT-A is an effective and safe treatment option for PPH.

Adverse Reactions After Intradermal Vaccination With JYNNEOS for Mpox in Korea.

In response to the Mpox domestic epidemic, South Korea initiated a nationwide vaccination program in May 2023, administering a 0.1 mL intradermal dose of JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to a high-risk group. To investigate the adverse reactions after intradermal JYNNEOS vaccination, an anonymous online survey was conducted at the National Medical Center from May 22 to July 31, 2023. Overall, 142 individuals responded. Over 80% of the respondents reported local reactions of predominantly mild severity. The predominant local reactions were pruritus, redness, and swelling; their incidence rates after the first dose were 66.2%, 48.1%, and 49.4%, respectively; the corresponding rates after the second dose were 69.2%, 60.6%, and 53.8%. Fewer respondents reported systemic symptoms. The most common systemic symptom was fatigue, the incidence rates of which after the first and second doses were 37.7% and 24.6%, respectively. Overall, the intradermally administered JYNNEOS vaccine appeared well tolerated.

Immediate SVF-Gel Injection Reduced Incision Scar Formation: A Prospective, Double-Blind, Randomized, Self-control Trial.

BACKGROUND: Skin incision scars are cosmetically displeasing; the effects of current treatments are limited, and new methods to reduce scar formation need to be found. OBJECTIVE: We sought to determine whether immediate postoperative injection of stromal vascular fraction gel (SVF-gel) could reduce scar formation at skin incision sites. METHODS: A prospective, randomized, double-blind, self-controlled trial was conducted in patients who underwent breast reduction. SVF-gel was intradermally injected into the surgical incision on one randomly selected side, with the other side receiving saline as a control. At the 6-month follow-up, the incision scars were evaluated using the Vancouver scar scale (VSS) and visual analog scale (VAS). Antera 3D camera was used for objective evaluation. RESULTS: The VSS score and VAS score were significantly different between the SVF-gel-treated side (3.80 ± 1.37, 3.37±1.25) and the control side (5.25 ± 1.18, 4.94 ± 1.28). Moreover, the SVF-gel-treated side showed statistically significant improvements in scar appearance, based on evidences from Antera 3D camera. LIMITATIONS: This was a single-center, single-race, and single-gender study. Furthermore, the results were available only for the 6-month interim follow-up period. CONCLUSION: Postoperative immediate SVF-gel injection in surgical incisions can reduce scar formation, and exert a preventive effect on scars. LEVEL OF EVIDENCE I: Evidence obtained from at least one properly designed randomized controlled trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Efficacy and Safety of Type III Collagen Lyophilized Fibers Using Mid-to-Deep Dermal Facial Injections for the Correction of Dynamic Facial Wrinkles.

BACKGROUND: This study aimed to evaluate the therapeutic efficacy and safety of injecting Type III collagen lyophilized fibers into the mid-to-deep layers of the facial dermis to ameliorate dynamic facial wrinkles. METHODS: In this retrospective analysis, clinical data were collected from patients exhibiting dynamic facial wrinkles (encompassing frown lines, forehead lines, and crow's feet) with a wrinkle severity rating scale (WSRS) score of 3 or higher. In the control group, 75 participants received collagen implant injections into the mid-to-deep facial dermal layers, whereas 76 participants in the experimental group received injections of Type III collagen lyophilized fibers in similar layers. The study analyzed and compared clinical efficacy, WSRS score alterations, patient satisfaction, and safety profiles between the groups over the 30-day and 90-day treatment periods. RESULTS: At the 30-day mark, the therapeutic efficacy was not significantly different between the two groups (P > 0.05). However, at 90 days, the treatment efficacy in the experimental group surpassed that in the control group, showing a statistically significant difference (P < 0.05). After 30 days of treatment, the WSRS score improvement in the experimental group was significantly superior to that in the control group (P < 0.05). Conversely, at the 90-day mark, the results revealed no significant variation in WSRS score improvements between the two groups (P > 0.05). Regarding treatment satisfaction among researchers and participants post-30 and 90-day treatment in both groups, no statistically significant differences were observed (P > 0.05). Similarly, the incidence of adverse reactions between the groups was not statistically significant (P > 0.05). CONCLUSIONS: Injections of lyophilized type III collagen fibers into the mid-to-deep layers of the facial dermis have a definitive therapeutic effect on dynamic facial wrinkles. This treatment not only substantially diminishes wrinkle severity but also has a commendable safety profile. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Low Molecular Weight Hyaluronic Acid Added to Six Specific Amino Acids in the Treatment of Striae Alba (SA): An Observational Study.

Striae distensae or stretch marks are a common complaint among women and can be distressing. The present study aimed to assess the efficacy of a mixture of low molecular weight hyaluronic acid and six amino acids when applied with a specific intradermal injection technique known as intra-mural fluid technique. A clinical study was carried out in 32 patients (with a dropout rate by 9.4%) with striae distensae alba (SA) in one or more of the following anatomical areas: breast, abdomen, inner thigh, trochanteric area, gluteal area, posterior supra-iliac area, and lumbar area. Product efficacy was assessed by the investigator using the Global Aesthetic Improvement Scale, while a Likert scale was used to evaluate to score the treatment tolerability and a QoL stretch marks questionnaire was used to investigate the patients' self-body image. The treatment was effective in improving the appearance of SA fifteen days after the second treatment and 6 months after the first treatment (and after a total of 4 treatments). The product efficacy and tolerability were also perceived by the patients during each treatment session. Our results suggest that the test treatment is a valid treatment option to decrease the appearance of SA. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266.

Different Dilutions of Mesobotox in Facial Rejuvenation: Which is Better?

BACKGROUND: Microbotulinum toxin A treatment is a technique of delivering multiple intradermal injections of diluted botulinum toxin type A into the dermis or the interface between the dermis and the superficial layer of the facial muscles to preserve the facial mobility. The current study aimed to evaluate and compare the clinical effect of different dilutions of microbotulinum toxin A in periorbital and mid-facial rejuvenation. METHODS: This randomized prospective interventional study included 30 female patients with different types of wrinkles in periorbital and/or mid-face. Patients were divided into three groups: group I (10 patients): 100U botulinum toxin in 5 ml saline, group II (10 patients): 100U botulinum toxin in 7 ml saline and group III (10 patients): 100U botulinum toxin in 10 ml saline. RESULTS: A statistically significant better global esthetic improvement scale (GAIS) scores after 1 month were observed in group I compared to groups II and III. Also, after 6 months better GAIS scores were observed in group I compared to group II and in group II compared to group III. Assessment of different esthetic parameters measured by the Antera 3D camera revealed a statistically significant improvement in all parameters (periorbital and mid-face) in group I and in most of parameters (periorbital and mid-face) in groups II and III with more evident improvement after 1 month compared to after 6 months. CONCLUSION: Intradermal microbotulinum toxin A is a cost-effective method for improving periorbital and mid-face wrinkles with a better effect of 1:5 than 1:7 and 1:10 dilutions. Facial wrinkles possess a great burden on patients' psychological status, and the emergence of novel rejuvenation technique with minimal side effects is necessary. MicroBoNT-A usage in the literature was through variety of dilutions and concentrations. Therefore, a conclusive and comparative study was essential to compare the effect of different microBoNT-A dilutions. In this context, the current study aimed to evaluate and compare the clinical effect of different dilutions of microBoNT-A in periorbital and mid-facial rejuvenation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intradermal Injection of Hybrid Complexes of High- and Low-Molecular-Weight Hyaluronan: Where Do We Stand and Where Are We Headed in Regenerative Medicine?

Hyaluronic acid (HA) is a remarkably multifaceted biomacromolecule, playing a role in regulating myriad biological processes such as wound healing, tissue regeneration, anti-inflammation, and immunomodulation. Crosslinked high- and low-molecular-weight hyaluronic acid hydrogels achieve higher molar concentrations, display slower degradation, and allow optimal tissue product diffusion, while harnessing the synergistic contribution of different-molecular-weight hyaluronans. A recent innovation in the world of hyaluronic acid synthesis is represented by NAHYCO® Hybrid Technology, a thermal process leading to hybrid cooperative hyaluronic acid complexes (HCC). This review summarizes the current literature on the in vitro studies and in vivo applications of HCC, from facial and body rejuvenation to future perspectives in skin wound healing, dermatology, and genitourinary pathologies.

Pre-Incisional and Multiple Intradermal Injection of N-Acetylcysteine Slightly Improves Incisional Wound Healing in an Animal Model.

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.

Simple Yet Effective-Sterile Water Injections to Treat Labor Pain in the Transport Environment.

Sterile water injections (SWI) is a nonpharmacologic pain relief option to treat back pain in labor. This case report describes and discusses the use of SWI in the context of an obstetric retrieval of a 29-year-old woman who was transferred by the Royal Flying Doctor Service South Eastern Section. It provides an overview of SWI, discusses the relevance for medical transport, and offers suggestions for medical transport professionals.

Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.

Induction of potent antitumor immunity by intradermal DNA injection using a novel needle-free pyro-drive jet injector.

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 ovalbumin (OVA) as a model antigen to investigate the potential of the PJI for vaccination against cancers. Intradermal injection of OVA-expression plasmid DNA into mice using the PJI, but not a needle syringe, rapidly and greatly augmented OVA-specific CD8+ T-cell expansion in lymph node cells. Increased mRNA expression of both interferon-γ and interleukin-4 and an enhanced proliferative response of OVA-specific CD8+ T cells, with fewer CD4+ T cells, were also observed. OVA-specific in vivo killing of the target cells and OVA-specific antibody production of both the IgG2a and IgG1 antibody subclasses were greatly augmented. Intradermal injection of OVA-expression plasmid DNA using the PJI showed stronger prophylactic and therapeutic effects against the progression of transplantable OVA-expressing E.G7-OVA tumor cells. Even compared with the most frequently used adjuvants, complete Freund's adjuvant and aluminum hydroxide with OVA protein, intradermal injection of OVA-expression plasmid DNA using the PJI showed a stronger CTL-dependent prophylactic effect. These results suggest that the novel needle-free PJI is a promising tool for DNA vaccination, inducing both a prophylactic and a therapeutic effect against cancers, because of prompt and strong generation of OVA-specific CTLs and subsequently enhanced production of both the IgG2a and IgG1 antibody subclasses.

Effects of Intradermal Administration Volume Using a Hollow Microneedle on the Pharmacokinetics of Fluorescein Isothiocyanate Dextran (M.W. 4,000).

PURPOSE: Hollow microneedles (hMNs) have been gaining attention as a tool to enable the intradermal (i.d.) administration of pharmaceutical products. However, few reports have examined the effect of administration volume on distribution in the skin and pharmacokinetics parameters after i.d. injection. In the present study, a model middle molecular weight compound, fluorescein isothiocyanate dextran (M.W. 4,000, FD-4), was selected, and blood concentration-time profiles after i.d. and subcutaneous (s.c.) injections with different administration volumes were compared. METHODS: FD-4 solution was injected i.d. using a hMN or injected s.c. with a 27 G needle. Pharmacokinetics and dermatokinetics of FD-4 were analyzed using a compartment model. The skin distribution of iodine, as an X ray tracer, was used to evaluate drug disposition. RESULTS: With the administered drug assumed to be absorbed from the broad injection site into blood vessels in the upper and lower dermis by rapid (krapid) and slow (kslow) first-order absorption rate constants, respectively, better agreement of observed and theoretical values was obtained. Furthermore, the fraction, F, of the administered dose absorbed with krapid decreased with the increase in injection volume after i.d. injection, although the pharmacokinetics parameters were almost the same regardless of administration volume after s.c. injection. CONCLUSION: The drug distribution in the skin may be related to the obtained pharmacokinetics parameters suggested that the number of needles in the MN system and the total administration volume should be considered in designing hMN systems. The present results provide useful information that may support effective drug delivery with hMNs.