Hyaluronan-based dissolving microneedles with high antigen content for intradermal vaccination: Formulation, physicochemical characterization and immunogenicity assessment

Leone, Marialucrezia; Priester, Marjolein I; Romeijn, Stefan; Nejadnik, M. Reza; Mönkäre, Juha; O’Mahony, Conor; Kersten, Gideon; Bouwstra, Joke A.

doi:10.1016/j.ejpb.2018.11.013

Cited by 46 publications

(42 citation statements)

References 47 publications

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“…Analysis of follicular helper T cells showed that the number of these cells after bolus injection peaked after 7 days, whilst similar levels were reached by microneedles after 14 days [ 79 ]. Biodegradable microneedles formed with gelatin methacryolyl have also shown potential for the sustained release of chemotherapeutics in vitro [ 115 ]. This method of sustained release may also be applied in vaccination.…”

Section: Vaccination Into the Dermal Compartment Without Needle Anmentioning

confidence: 99%

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

Hettinga

Carlisle

2020

Vaccines

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In 2019, an ‘influenza pandemic’ and ‘vaccine hesitancy’ were listed as two of the top 10 challenges to global health by the WHO. The skin is a unique vaccination site, due to its immune-rich milieu, which is evolutionarily primed to respond to challenge, and its ability to induce both humoral and cellular immunity. Vaccination into this dermal compartment offers a way of addressing both of the challenges presented by the WHO, as well as opening up avenues for novel vaccine formulation and dose-sparing strategies to enter the clinic. This review will provide an overview of the diverse range of vaccination techniques available to target the dermal compartment, as well as their current state, challenges, and prospects, and touch upon the formulations that have been developed to maximally benefit from these new techniques. These include needle and syringe techniques, microneedles, DNA tattooing, jet and ballistic delivery, and skin permeabilization techniques, including thermal ablation, chemical enhancers, ablation, electroporation, iontophoresis, and sonophoresis.

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Section: Vaccination Into the Dermal Compartment Without Needle Anmentioning

confidence: 99%

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

Hettinga

Carlisle

2020

Vaccines

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“…Dissolving MNAs (dMNAs) were fabricated by micromolding technique, pouring a solution of 10% ( w / v ) hyaluronan (HA) in 10 mM phosphate buffer (pH 7.4) in a PDMS mold. The PDMS mold was prepared by pouring and letting cure a PDMS solution consisting of a mixture of a silicone elastomer and silicone elastomer curing agent (10:1 ratio) on a template presenting Tyndall MNAs [27] (see Table 1). dMNA and dMNA featuring a back-plate part (dMNA-BP) of vinylpolysiloxane and epoxy glue were prepared using two different PDMS mold designs (Figure 1) [27].…”

Section: Methodsmentioning

confidence: 99%

Universal Applicator for Digitally-Controlled Pressing Force and Impact Velocity Insertion of Microneedles into Skin

et al. 2018

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Microneedle technologies have been developed for dermal drug and vaccine delivery, including hollow-, solid-, coated-, and dissolving microneedles. Microneedles have been made in many different geometries and of many different materials, all of which may influence their skin-penetrating ability. To ensure reproducible and effective drug and vaccine delivery via microneedles, the optimal insertion parameters should be known. Therefore, a digitally-controlled microneedle applicator was developed to insert microneedles into the skin via impact insertion (velocity) or via pressing force insertion. Six microneedle arrays with different geometries and/or materials were applied onto ex vivo human skin with varying velocities or pressing forces. Penetration efficiency and delivered antigen dose into the skin after application of microneedles were determined. In general, microneedles pierced the skin more efficiently when applied by impact application as compared to application via pressing force. However, the angle of application of the applicator on the skin can affect the velocity of the impact, influencing the penetration efficiency of microneedles. Regarding the antigen delivery into the skin, the delivered dose was increasing by increasing the velocity or pressure, and thus, increasing the penetration efficiency. These data demonstrate that an applicator is an important tool to determine optimal application conditions with ex vivo human skin.

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“…reported that the hollow MN‐mediated intradermal delivery of the model antigen ovalbumin encapsulated in polymeric nanoparticles is a promising approach to improve the effectiveness of vaccine formulations. Similarly, promising results have been obtained in the case of HA‐based dissolving MNs with high antigen content for intradermal vaccination …”

Section: Therapeutics and Beyondmentioning

confidence: 98%

“…[33] They hypothesized that the delivery of a DNA vaccine into the skin by MNs could improve the immune response by enhancing the protein expression of the encoded gene. [37] Additionally, a widely used, poorly soluble drug, namely, granisetron, a specific 5-HT3 receptor antagonist that prevents nausea and vomiting in cancer patients during emetogenic chemotherapy, was used as a model lipophilic drug and found to benefit greatly from the use of MNs. [34] A suitable formulation of the MN patches exhibited superior thermostability that could enable the mass distribution of IPV vaccines with less dependence on cold chain storage.…”

Section: Therapeutics and Beyondmentioning

confidence: 99%

“…Coated (33) Dissolving (34), (35), (37), (43) Swelling (35) Hollow (36) In vivo (mouse) In vitro [33,[35][36][37]43] [ 34] Nausea and vomiting Swelling In vivo [38] Obesity Dissolving In vivo (mouse) [40,41] Keloid scar Swelling Ex vivo [42] Vitamin K deficiency Dissolving In vitro [44] have been loaded into MNs and effectively administered both in vitro and in vivo. [42][43][44] The spectrum of substances proven to be compatible with MN technology is wide.…”

Section: Warts Coatedmentioning

confidence: 99%

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Polymeric Microneedle Arrays: Versatile Tools for an Innovative Approach to Drug Administration

Dardano

Battisti²,

Rea

et al. 2019

Advanced Therapeutics

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Mainly designed and realized as a painless alternative to the hypodermic syringe, microneedle-based devices are currently approaching commercial market placement. The considerable academic and industrial investment in this technology is reflected by a multitude of papers published and patents registered every year, which is also a sign of a field in full fermentation. New materials and innovative methodologies are continuously exploited in search of the best performance at the lowest cost. For these reasons, an updated review, focused predominantly on the last year of scientific production, is a useful guideline in this rapidly changing panorama. This report provides a critical review of microneedle technologies presented in the very recent literature with a particular focus on those closest to the needs of the healthcare field. Although a few devices are already commercial, further effort is still needed to achieve complete clinical translation and therapeutic efficacy competitive with or superior to those of the devices used as standards and adopted by national health systems.

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Hyaluronan-based dissolving microneedles with high antigen content for intradermal vaccination: Formulation, physicochemical characterization and immunogenicity assessment

Cited by 46 publications

References 47 publications

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

Universal Applicator for Digitally-Controlled Pressing Force and Impact Velocity Insertion of Microneedles into Skin

Polymeric Microneedle Arrays: Versatile Tools for an Innovative Approach to Drug Administration

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