Antigen-loaded dissolving microneedle array as a novel tool for percutaneous vaccination

Naito, Seishiro; Ito, Yoshiaki; Kiyohara, Tomoko; Kataoka, Michiyo; Ochiai, Masaki; Takada, Kanji

doi:10.1016/j.vaccine.2011.11.111

Cited by 60 publications

(43 citation statements)

References 35 publications

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“…In this point of view, various approaches have performed to penetrate vaccine across the skin such as solid multi-needles systems which possess well-controlled needles length, hollow single needle systems aim to reliable injection [12, 13], transdermal patches in order to self-administration of vaccines [37]. Biodegradable polymeric technology enables novel vaccines with antigen-loaded dissolvable microneedles [38, 39]. However, as we indicated opposite effect of IgG and IgE production between epicutaneous and intradermal administration, immunogenicity of vaccine could be different even among these similar skin delivery devices.…”

Section: Discussionmentioning

confidence: 99%

Intradermal Delivery of Antigens Enhances Specific IgG and Diminishes IgE Production: Potential Use for Vaccination and Allergy Immunotherapy

et al. 2016

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Skin is protected by a tough but flexible multilayered barrier and is a front line for immune responses against invading particles. For many years now, skin has been a tissue where certain vaccines are injected for the prevention of infectious disease, however, the detailed mechanisms of the skin immune response are not yet well understood. Using thin and small injection needles, we carefully injected OVA into a restricted region of mouse skin, i.e., intradermal (ID), and examined the antibody response in comparison with subcutaneous (SC) injection or epicutaneous patch administration of OVA. Epicutaneous patches induced a high IgE response against OVA, but IgG production was low. High IgG production was induced by both ID and SC injection, moreover, ID injection induced higher IgG production without any adjutants. Furthermore, OVA-specific IgE production was diminished by ID injection. We found that ID injection could efficiently stimulate skin resident DCs, drive Th1-biased conditions and diminish IgE production. The ID injection response was regulated by Langerin+ dermal DCs, because OVA was taken up mainly by these cells and, after transiently deleting them, the IgE response was no longer diminished and IgG1 production was enhanced. We also tested whether ID injection might be an effective allergy treatment by attempting to inhibit ongoing IgE production in mice with experimentally induced high serum IgE levels. Multiple ID injections of OVA were shown to prevent elevation of serum OVA-specific IgE after repeated allergen challenge. In contrast, SC OVA injection could only transiently inhibit the OVA-specific IgE production. These findings indicated that ID injection results in higher induction of antigen-specific IgG, and thus may be useful for vaccine delivery with little or no adjuvant components. Moreover, the observed diminishment of IgE and induction of Th1-biased immune responses suggest that ID may be a useful injection route for allergy immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Intradermal Delivery of Antigens Enhances Specific IgG and Diminishes IgE Production: Potential Use for Vaccination and Allergy Immunotherapy

et al. 2016

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“…We chose these needle sizes because the usefulness of these microneedles are commonly investigated. 17,19,37) Microneedles having a needle length of 500 µm were likely to be more effective than 300-µm microneedles in terms of activation of MHC class II on LCs (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

“…These techniques include powder injection, 9,10) iontophoresis, 11,12) sonophoresis, 13,14) patch formulations, 15,16) and microneedles. [17][18][19] In recent years, the use of microneedles has emerged as a novel invasive technique. Microneedles reliably penetrate through the stratum corneum and can create an efficient permeation pathway into the skin and consequently improve the delivery of high-molecular-weight substances including antigens.…”

mentioning

confidence: 99%

Application of Microneedles to Skin Induces Activation of Epidermal Langerhans Cells and Dermal Dendritic Cells in Mice

Takeuchi

Nomoto

Watanabe

et al. 2016

Biological & Pharmaceutical Bulletin

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An adequate immune response to percutaneous vaccine application is generated by delivery of sufficient amounts of antigen to skin and by administration of toxin adjuvants or invasive skin abrasion that leads to an adjuvant effect. Microneedles penetrate the stratum corneum, the outermost layer of the skin, and enable direct delivery of vaccines from the surface into the skin, where immunocompetent dendritic cells are densely distributed. However, whether the application of microneedles to the skin activates antigen-presenting cells (APCs) has not been demonstrated. Here we aimed to demonstrate that microneedles may act as a potent physical adjuvant for successful transcutaneous immunization (TCI). We prepared samples of isolated epidermal and dermal cells and analyzed the expression of major histocompatibility complex (MHC) class II and costimulatory molecules on Langerhans or dermal dendritic cells in the prepared samples using flow cytometry. The expression of MHC class II and costimulatory molecules demonstrated an upward trend in APCs in the skin after the application of 500-and 300-µm microneedles. In addition, in the epidermal cells, application of microneedles induced more effective activation of Langerhans cells than did an invasive tapestripping (positive control). In conclusion, the use of microneedles is likely to have a positive effect not only as an antigen delivery system but also as a physical technique inducing an adjuvant-like effect for TCI.

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“…Dissolving MN arrays have been shown to enhance transdermal and intradermal delivery of numerous substances, including insulin [1,2], 5-aminolevulinic acid [3], sulforhodamine B [4], low molecular weight heparin [5], ovalbumin [6,7], adenovirus vector [7] and a variety of vaccine antigens [8,9]. Synergistic effects of dissolving MN arrays used in combination with other enhancing strategies have been reported recently by Garland et al [10], where the use of drug-loaded dissolving poly(methyl-vinyl-ether-co-maleic-acid) MN arrays was coupled with iontophoresis.…”

Section: Introductionmentioning

confidence: 99%

Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

McCrudden

Alkilani

McCrudden

et al. 2014

Journal of Controlled Release

201

112

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We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5 mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33 mg (90%) of the drug initially loaded into the arrays was delivered over 24 h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263 μg ml− 1 at the 24 h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10 cm2 could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs.

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Antigen-loaded dissolving microneedle array as a novel tool for percutaneous vaccination

Cited by 60 publications

References 35 publications

Intradermal Delivery of Antigens Enhances Specific IgG and Diminishes IgE Production: Potential Use for Vaccination and Allergy Immunotherapy

Intradermal Delivery of Antigens Enhances Specific IgG and Diminishes IgE Production: Potential Use for Vaccination and Allergy Immunotherapy

Application of Microneedles to Skin Induces Activation of Epidermal Langerhans Cells and Dermal Dendritic Cells in Mice

Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

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