In Vivo, In Situ Imaging of Microneedle Insertion into the Skin of Human Volunteers Using Optical Coherence Tomography

Coulman, Sion; Birchall, James Caradoc; Alex, Aneesh; Pearton, Marc; Höfer, Bernd; O’Mahony, Conor; Drexler, Wolfgang; Považay, Boris

doi:10.1007/s11095-010-0167-x

Cited by 111 publications

(67 citation statements)

References 52 publications

(68 reference statements)

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“…Even though they speculate that the in vitro condition could have overestimated the pore size by 20%, the observed phenomenon indicates the significance of the role of skin's elasticity in resealing (25). The role of skin's elasticity and other biomechanical properties can perhaps be directly investigated with new emerging techniques such as OCT which enables direct in vivo imaging of the microporation process (26). It should also be noted that age, skin site, and application pressure will also play significant roles in pore closure kinetics.…”

Section: Resultsmentioning

confidence: 99%

Characterization of Microchannels Created by Metal Microneedles: Formation and Closure

Kalluri

Kolli²,

Banga

2011

AAPS J

120

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Abstract. Transdermal delivery of therapeutic agents for cosmetic therapy is limited to small and lipophilic molecules by the stratum corneum barrier. Microneedle technology overcomes this barrier and offers a minimally invasive and painless route of administration. DermaRoller ® , a commercially available handheld device, has metal microneedles embedded on its surface which offers a means of microporation. We have characterized the microneedles and the microchannels created by these microneedles in a hairless rat model, using models with 370 and 770 μm long microneedles. Scanning electron microscopy was employed to study the geometry and dimensions of the metal microneedles. Dye binding studies, histological sectioning, and confocal microscopy were performed to characterize the created microchannels. Recovery of skin barrier function after poration was studied via transepidermal water loss (TEWL) measurements, and direct observation of the pore closure process was investigated via calcein imaging. Characterization studies indicate that 770 μm long metal microneedles with an average base width of 140 μm and a sharp tip with a radius of 4 μm effectively created microchannels in the skin with an average depth of 152.5±9.6 μm and a surface diameter of 70.7±9.9 μm. TEWL measurements indicated that skin regains it barrier function around 4 to 5 h after poration, for both 370 and 770 μm microneedles. However, direct observation of pore closure, by calcein imaging, indicated that pores closed by 12 h for 370 μm microneedles and by 18 h for 770 μm microneedles. Pore closure can be further delayed significantly under occluded conditions.

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Section: Resultsmentioning

confidence: 99%

Characterization of Microchannels Created by Metal Microneedles: Formation and Closure

Kalluri

Kolli²,

Banga

2011

AAPS J

120

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“…A notable limitation to this method is that lateral diffusion of dyes can lead to overestimation of micropore diameter [56]. Another problem with the method is that sometimes the SC is not truly pierced and methylene blue pools in the indentions creating false positives.…”

Section: Staining Of Microneedle-treated Skinmentioning

confidence: 99%

“…Furthermore, it is often difficult to locate the MN perforation in the skin sample due to the irregular nature of this tissue, as illustrated in the figure. Coulman et al [56] recognised analysing MN-mediated pore dimensions via histological methods leads to overestimation of measurements. This was highlighted through comparison of histological microchannel images taken in a previous study [67] with OCT images produced by the same type of silicon MNs.…”

Section: Histological Tissue Staining and Sectioningmentioning

confidence: 99%

“…The ability of OCT to visualise depths of ̴ 2000 µm demonstrates this technique's superiority over confocal microscopy, which is only capable of penetrating to 200-250 µm depths. OCT can therefore be considered as the only technique capable of providing transverse imaging of the SC, epidermis and upper dermis [5,43,56,68,70]. OCT is a valuable, non-invasive technique that can be used to observe (Figure 10), in real time, MNs inserted into human subjects' skin to determine the MNs' ability to penetrate the skin [5].…”

Section: Optical Coherence Tomographymentioning

confidence: 99%

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Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation

Lutton

Moore

Larrañeta

et al. 2015

Drug Deliv. and Transl. Res.

106

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“…On a separate note, the skin's integrity post incisions or MN applications has been measured by several non-invasive techniques such as Trans-Epidermal Water Loss measurements (TEWL) [332,593], electrical impedance measurements [594], infrared spectroscopy [595], confocal microscopy [223,596] and optical coherence tomography [597]. TEWL data can assist in defining the required time for the skin to re-establish its barrier function.…”

Section: Introductionmentioning

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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In Vivo, In Situ Imaging of Microneedle Insertion into the Skin of Human Volunteers Using Optical Coherence Tomography

Abstract: Microchannels created in the upper skin layers by microneedles are less invasive than previous histology predicts. OCT has the potential to play a highly influential role in the future development of microneedle devices and other transdermal delivery systems.

Cited by 111 publications

References 52 publications

Characterization of Microchannels Created by Metal Microneedles: Formation and Closure

Characterization of Microchannels Created by Metal Microneedles: Formation and Closure

Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation

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

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