Successful application of large microneedle patches by human volunteers

Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente‐Pérez, Eva M.; Barry, Johanne; Donnelly, Ryan F.

doi:10.1016/j.ijpharm.2017.02.011

Cited by 157 publications

(128 citation statements)

References 23 publications

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“…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.…”

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confidence: 99%

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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confidence: 99%

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

et al. 2019

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“…By attaching this membrane, which displays a color‐change when pressure sufficient to breach the stratum corneum is applied to the MNs, a visual assurance is provided to users that the MNs have been correctly inserted. This, coupled with recent results showing that volunteers following written instructions were capable of reliably applying MN patches of variable sizes, suggests that manual insertion could be a viable technique upon clinical translation, for both drug delivery and diagnostic applications of MN technologies …”

Section: Translational Considerationsmentioning

confidence: 77%

Advances in the Design of Transdermal Microneedles for Diagnostic and Monitoring Applications

Babity

Roohnikan

Brambilla

2018

Small

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Due to their intrinsic advantages over classical hypodermic needles, microneedles have received much attention over the last two decades and will likely soon appear in clinics. Although the vast majority of research is focused on designing microneedles for the painless delivery of drugs, their applications for diagnostic purposes have also provided promising results. In this paper, the main advances in the field of microneedles for diagnostic and patient monitoring purposes are introduced and critically discussed.

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“…This approach is also straightforward, requiring little equipment and is cost effective. The lack of visual needles and possibility for self-application is likely to prove beneficial with regard to needle phobia and limiting the requirement for trained personnel [120]. In the case of dissolving MN, the needles dissolve within the skin and there is no requirement for appropriate needle disposal or the fear of needle reuse, thus, prohibiting the possibility of disease transmission.…”

Section: Discussionmentioning

confidence: 99%

Microneedle arrays for vaccine delivery: the possibilities, challenges and use of nanoparticles as a combinatorial approach for enhanced vaccine immunogenicity

Rodgers

Cordeiro

Kissenpfennig

et al. 2018

Expert Opinion on Drug Delivery

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Vaccination is one of the greatest breakthroughs of modern preventative medicine. Despite this, there remain problems surrounding delivery, efficacy and compliance. Thus, there is a pressing need to develop cost-effective vaccine delivery systems that could expand the use of vaccines, particularly within developing countries. Microneedle (MN) arrays, given their ease of use, painlessness and ability to target skin antigen presenting cells, provide an attractive platform for improved vaccine delivery and efficacy. Studies have demonstrated enhanced immunogenicity with the use of MN in comparison to conventional needle. More recently, dissolving MN have been used for efficient delivery of nanoparticles (NP), as a means to enhance antigen immunogenicity. Areas covered: This review introduces the fields of MN technology and nanotechnology, highlighting the recent advances which have been made with these two technologies combined for enhanced vaccine delivery and efficacy. Some key questions that remain to be addressed for adoption of MN in a clinical setting are also evaluated. Expert opinion: MN-mediated vaccine delivery holds potential for expanding access to vaccines, with individuals in developing countries likely to be the principal beneficiaries. The combinatorial approach of utilizing MN coupled with NP, provides opportunities to enhance the immunogenicity of vaccine antigens.

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Successful application of large microneedle patches by human volunteers

Abstract: Graphical abstract

Cited by 157 publications

References 23 publications

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

Advances in the Design of Transdermal Microneedles for Diagnostic and Monitoring Applications

Microneedle arrays for vaccine delivery: the possibilities, challenges and use of nanoparticles as a combinatorial approach for enhanced vaccine immunogenicity

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