Design and characterisation of a dissolving microneedle patch for intradermal vaccination with heat-inactivated bacteria: A proof of concept study

Rodgers, Aoife M.; McCrudden, Maeliosa; Vincente-Perez, Eva.M.; Dubois, Alice; Ingram, Rebecca J.; Larrañeta, Eneko; Kissenpfennig, Adrien; Donnelly, Ryan F.

doi:10.1016/j.ijpharm.2018.07.049

Cited by 40 publications

(48 citation statements)

References 30 publications

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“…MNs were prepared by using Gantrez ® , a poly(methyl vinyl ether-co-maleic anhydride) polymer, which has been extensively employed for pharmaceutical applications, such as denture adhesives, thickening, suspending agents, or carriers for oral delivery, due to its mucoadhesive properties and low oral toxicity [31]. More recently, it has been used for the preparation of transdermal patches, showing good properties to form dissolving MNs [14,32]. Among the different types of Gantrez ® polymers used, Gantrez ® AN119 has not been reported to perform MNs.…”

Section: Discussionmentioning

confidence: 99%

“…In a first in vivo study, a comparison between Gantrez ® AN119 and the polymers AN139 and S97 already used in other studies [11,14,34] was performed. Comparative immunization and protection results did not show significant differences between polymers.…”

Section: Discussionmentioning

confidence: 99%

“…Soluble protein antigens, such as toxoids, can be readily incorporated in the MNs matrix, however, the delivery of amphipathic structures is not so widely studied. To our knowledge, there is only one previous publication studying the potential of dissolving MNs for the delivery of non-toxoid bacterial antigens [14]. However, it was considered only as a basic proof of concept, since studies were not carried out to elucidate the mechanism involved.The aim of the present study was to design and develop a dissolving MN patch made of aqueous blends of w/w poly (methyl vinyl ether-co-maleic anhydride), commercialized as Gantrez AN ® (Gz), which is not cytotoxic and has been shown to posses immunoadjuvant properties [15,16] and evaluate its capacity for ID vaccination.…”

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confidence: 99%

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confidence: 99%

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Dissolving Microneedles for Intradermal Vaccination against Shigellosis

et al. 2019

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Intradermal (ID) immunization is of increasing interest due to the easy accessibility and excellent immunogenic properties of the skin. Among ID immunization methods, dissolving microneedles (MNs) have appeared as an alternative to traditional hypodermic immunization, offering many advantages, such as being an easily administered method, with no need for health personnel, painless, and avoiding the use of needles and sharp wastage. In this study, an affordable and easy-to-produce MNs method was developed based on aqueous blends of 30% w/w poly (methyl vinyl ether-co-maleic anhydride). As an antigen model, a subunit vaccine candidate based on outer membrane vesicles from Shigella flexneri was used. Both unloaded and antigen-loaded MNs were synthetized and characterized. The MNs were successfully validated in an in vitro Parafilm M ® skin model and in a pig skin ex vivo model. Biodistribution studies were performed in BALB/c mice using 99m TcO 4 − radiolabeled samples. Results indicated that the vesicle vaccine was successfully released from the MNs and targeted gastrointestinal tract after 6 h post-administration. In vivo immunization and protection studies were performed in BALB/c mice. Mice were intradermally immunized through ear skin with one single dose of 200 µg antigenic complex, eliciting the production of specific systemic IgG and mucosal IgA. Moreover, MNs were able to protect mice from an experimental infection with 1×10 6 CFU/mouse of S. flexneri four weeks after immunization. This work demonstrates for the first time the potential of outer membrane vesicle-loaded dissolving MNs for ID vaccination against enteropathogens like Shigella.Vaccines 2019, 7, 159 2 of 15 (SALT), formed by a great network of immune cells, including Langerhans cells (LC), lymphocytes, and dendritic cells (DCs), which recognize the antigens and present them in the proximal lymph nodes [3]. Different ID vaccination methods have been used already, such as the Mantoux technique, microinjection systems, or jet injectors, used for smallpox, rabies, or Bacillus Calmette-Guérin (BCG) vaccines. However, they require the use of needles [4]. Microneedle patches (MNs) have appeared as a novel and attractive approach for ID immunization [5]. They are painless devices formed by arrays of micron-size projections that can pass through the stratum corneum and epidermis without reaching the nerves of the dermis layer [6]. Thus, they are a self-administered, minimally invasive method, well tolerated by human patients in proof of concept trials [7,8], that can directly target the skin immune cells [9].Several types of MNs have been developed for the delivery of antigens: solid, coated, hollow, and dissolving MNs [10]. Among them, and based on their self-disabling properties, dissolving MNs (MNs) have been selected for this work. These MNs are made of a soluble matrix, generally a biocompatible polymer or polysaccharide, which includes the antigenic complex. After the array insertion into the skin, the needle tips dissolve and the antigenic cargo i...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Dissolving Microneedles for Intradermal Vaccination against Shigellosis

et al. 2019

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“…polymer, and as such, this polymer was used to fabricate robust MN for the experiments conducted herein [11]. It is well known that a number of Gantrez ® products have been shown to produce adjuvant effects [18,19].…”

Section: Discussionmentioning

confidence: 99%

Novel Hydrogel-Forming Microneedle Array for Intradermal Vaccination in Mice Using Ovalbumin as a Model Protein Antigen

et al. 2018

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Global vaccination strategies have traditionally relied on the hypodermic needle and syringe model. However, to facilitate increased immunisation coverage and reduce costs, novel methods of vaccine delivery are warranted. Dissolving microneedle arrays (MN) have been proposed as an alternative approach to the hypodermic needle, offering the prospect for selfvaccination and increased immunogenicity via direct targeting of skin dendritic cells. This study, for the first time, compares the use of novel hydrogel-forming MNs and dissolving MNs for the delivery of a model protein antigen ovalbumin (OVA). We provide comparative data on both MN types in terms of in vitro characteristics and in vivo immunogenicity. Herein, both MN platforms were tested and characterised in terms of mechanical integrity and insertion properties using a validated skin insertion model. A comparative in vivo vaccination study in balb/c mice was conducted, whereby anti-OVA specific IgG was used as a measure of delivery efficacy and subsequent immune response. While vaccination of mice with both MN platforms resulted in IgG responses, those vaccinated with dissolving MNs had significantly higher IgG titres (p < 0.0149), despite the quantity of OVA delivered being significantly less. This study highlights the importance of MN design and the potential impact of dissolving MN polymers on the immune response to vaccine antigens. Further, detailed studies, are therefore required to elucidate the effects of polymer-vaccine interactions and their subsequent effect on immune responses.

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Advances in Antimicrobial Microneedle Patches for Combating Infections

et al. 2020

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Skin infections caused by bacteria, viruses and fungi are difficult to treat by conventional topical administration because of poor drug penetration across the stratum corneum. This results in low bioavailability of drugs to the infection site, as well as the lack of prolonged release. Emerging antimicrobial transdermal and ocular microneedle patches have become promising medical devices for the delivery of various antibacterial, antifungal, and antiviral therapeutics. In the present review, skin anatomy and its barriers along with skin infection are discussed. Potential strategies for designing antimicrobial microneedles and their targeted therapy are outlined. Finally, biosensing microneedle patches associated with personalized drug therapy and selective toxicity toward specific microbial species are discussed.

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Design and characterisation of a dissolving microneedle patch for intradermal vaccination with heat-inactivated bacteria: A proof of concept study

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Cited by 40 publications

References 30 publications

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

Novel Hydrogel-Forming Microneedle Array for Intradermal Vaccination in Mice Using Ovalbumin as a Model Protein Antigen

Advances in Antimicrobial Microneedle Patches for Combating Infections

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