Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice

Ding, Zhi; Verbaan, FJ; Bivas-Benita, Maytal; Bungener, Laura; Huckriede, Anke; Berg, Dirk–Jan van den; Kersten, Gideon; Bouwstra, Joke A.

doi:10.1016/j.jconrel.2009.01.025

Cited by 140 publications

(79 citation statements)

References 36 publications

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“…One of these microneedle arrays was selected to compare the penetration of a fluorescent dye applied in solution with that applied in liposomes. The microneedle arrays that were used in the present study have already been proven to be painless (Bal et al, 2008) and were shown to be efficient in enhancing the immune response when applying Diphtheria Toxoid as an antigen (Ding et al, 2009). In the present study, the model drug fluorescein was used.…”

Section: A C Bmentioning

confidence: 90%

“…Furthermore, compared to piercing with a conventional needle, there is only a minimal microbial infiltration through the conduits, and microorganisms do not reach the dermis (Donnelly et al, 2009). More recently, microneedles have also been used for vaccination (Ding et al, 2009, Kim et al, 2009, Koutsonanos et al, 2009, Matriano et al, 2002, Widera et al, 2006. Several studies have shown that the use of microneedles increases the efficiency of vaccination (Ding et al, 2009, Matriano et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…More recently, microneedles have also been used for vaccination (Ding et al, 2009, Kim et al, 2009, Koutsonanos et al, 2009, Matriano et al, 2002, Widera et al, 2006. Several studies have shown that the use of microneedles increases the efficiency of vaccination (Ding et al, 2009, Matriano et al, 2002). In addition, microneedles can be used in combination with nanoparticles that may increase the transport of antigens or low molecular weight substances across the conduits (Bal et al, 2010a).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Application of in vivo Laser Scanning Microscopy to Visualise the Penetration of a Fluorescent Dye in Solution and in Liposomes into the Skin after Pre-Treatment with Microneedles

Martina¹,

Annelieke²,

Suzanne³

et al. 2011

Laser Scanning, Theory and Applications

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Section: A C Bmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Application of in vivo Laser Scanning Microscopy to Visualise the Penetration of a Fluorescent Dye in Solution and in Liposomes into the Skin after Pre-Treatment with Microneedles

Martina¹,

Annelieke²,

Suzanne³

et al. 2011

Laser Scanning, Theory and Applications

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“…In general, administration of solid MNs achieved equivalent if not increased immune responses to DT [51], influenza [89,196,289,[309][310][311], OVA [262,266,275,280] MN-immunised mice were also protected against lethal challenge 3 months after immunisations.…”

Section: Solid Microneedlesmentioning

confidence: 93%

“…or i.n. administration with a DNA vaccine against HIV immunisation experiments similar to CpG [51], others reported a more balanced (IgG1:IgG2a ratio) response following the mucosal administration of saponins [408]. Further, antigen and species-dependency with ginsenosides have also been observed, inducing either Th1 or Th2 responses [418]; ginsenoside type Rb1 illustrated Th1 or Th2 responses following pneumococcal polysaccharide vaccine administration [419].…”

Section: Advantages and Disadvantages Associated With Adjuvantsmentioning

confidence: 99%

Investigation of cell death caused by the Nanopatch™ and its role in vaccine delivery as a physical immune enhancer

Depelsenaire¹

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Since the introduction of vaccines, millions of lives have been saved. Yet, infectious diseases continue to contribute to deaths in underdeveloped countries, with over 2 million children dying per year from preventable diseases such as diphtheria, pertussis and tetanus. Despite the advantages of vaccines, there are also some risks and disadvantages associated with vaccines and their delivery such as the need for medical personnel for administration, refrigeration of the vaccine, disease transmission associated with needles and potential adverse side effects due to adjuvants. While intramuscular and subcutaneous injections are most frequently used for vaccine administration, these sites are poor in antigen-presenting cells. The skin, the largest immunological organ, by contrast contains a dense network of antigen-presenting cells, important in the uptake of antigen and presentation to naive T-cells, and has received increased interest as a target site for vaccine delivery. Intradermal immunisations have achieved significant dose-sparing over conventional immunisation routes. However, using existing needle designs, intradermal injections can be difficult to administer into the thin dermal layer due to the proportionally large scale of the needle. This has led to the development of alternative skin-based delivery methods, such as microneedle arrays.Here, the Nanopatch™ is an array containing 3364 microprojections of ~110 µm in length, which was used to deliver the vaccine into the viable epidermis and dermis of the skin. With an unprecedented >100-fold dose-sparing reported by the Nanopatch™ in comparison to conventional immunisation strategies with an influenza split virion vaccine, the mechanisms behind this skin- The extent of cell death after Nanopatch™ application and intradermal injection was investigated, characterised and quantified by Confocal/ Multiphoton microscopy, Western Blot and flow cytometry. A distinct pattern of dead cells was obtained with significantly higher levels (~65-fold) of cell death in murine ear skin following Nanopatch™ treatment than intradermal injection.ii | P a g e Measured skin cell death was tuneable by changing projection density but not shapes, and was associated with modelled stresses of ≥1 MPa.Immunogenicity studies demonstrated consistently and statistically significantly higher anti-IgG endpoint titres (up to 50-fold higher) in Nanopatch™ than intradermally injected groups after delivery of a split virion influenza vaccine, with a 10-fold dose-sparing effect. Importantly, colocalisation of delivered antigen with both, live and dead cells was necessary for immunogenicity enhancement. Overall, higher inflammatory responses and longer-lasting antigen depot formation were associated with Nanopatch™ immunisations but not with intradermal injections. The findings indicated a correlation between co-localisation of antigen cell death caused by the Nanopatch™ and enhanced immunogenicity with split virion influenza vaccine as model antigen.Collectively, the data presented wi...

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Transdermal Delivery of Drugs Using Patches and Patchless Delivery Systems

et al. 2016

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Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice

Cited by 140 publications

References 36 publications

Application of in vivo Laser Scanning Microscopy to Visualise the Penetration of a Fluorescent Dye in Solution and in Liposomes into the Skin after Pre-Treatment with Microneedles

Application of in vivo Laser Scanning Microscopy to Visualise the Penetration of a Fluorescent Dye in Solution and in Liposomes into the Skin after Pre-Treatment with Microneedles

Investigation of cell death caused by the Nanopatch™ and its role in vaccine delivery as a physical immune enhancer

Transdermal Delivery of Drugs Using Patches and Patchless Delivery Systems

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