A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin

Nicole M. D. van der Burg, Alexandra C. I. Depelsenaire, Michael L. Crichton, Paula Kuo, Simon Phipps, Mark A. F. Kendall

Research output: Contribution to journalArticle

Abstract

In a low inflammatory skin environment, Langerhans cells (LCs) - but not dermal dendritic cells (dDCs) - contribute to the pivotal process of tolerance induction. Thus LCs are a target for specific-tolerance therapies. LCs reside just below the stratum corneum, within the skin's viable epidermis. One way to precisely deliver immunotherapies to LCs while remaining minimally invasive is with a skin delivery device such as a microprojection arrays (MPA). Today's MPAs currently achieve rapid delivery (e.g. within minutes of application), but are focussed primarily at delivery of therapeutics to the dermis, deeper within the skin. Indeed, no MPA currently delivers specifically to the epidermal LCs of mouse skin. Without any convenient, pre-clinical device available, advancement of LC-targeted therapies has been limited. In this study, we designed and tested a novel MPA that delivers ovalbumin to the mouse epidermis (eMPA) while maintaining a low, local inflammatory response (as defined by low erythema after 24 h). In comparison to available dermal-targeted MPAs (dMPA), only eMPAs with larger projection tip surface areas achieved shallow epidermal penetration at a low application energy. The eMPA characterised here induced significantly less erythema after 24 h (p = 0.0004), less epidermal swelling after 72 h (p < 0.0001) and 52% less epidermal cell death than the dMPA. Despite these differences in skin inflammation, the eMPA and dMPA promoted similar levels of LC migration out of the skin. However, only the eMPA promoted LCs to migrate with a low MHC II expression and in the absence of dDC migration. Implementing this more mouse-appropriate and low-inflammatory eMPA device to deliver potential immunotherapeutics could improve the practicality and cell-specific targeting of such therapeutics in the pre-clinical stage. Leading to more opportunities for LC-targeted therapeutics such as for allergy immunotherapy and asthma.

LanguageEnglish
Pages190-200
Number of pages11
JournalJournal of Controlled Release
Volume302
Early online date30 Mar 2019
DOIs
Publication statusE-pub ahead of print - 30 Mar 2019

Fingerprint

Langerhans Cells
Ovalbumin
Epidermis
Skin
Erythema
Equipment and Supplies
Immunotherapy
Therapeutics
Dermis
Cell- and Tissue-Based Therapy
Cornea
Cell Movement
Hypersensitivity
Cell Death
Asthma
Inflammation

Keywords

  • Epidermis
  • Langerhans cell targeting
  • Microneedle
  • Microprojection
  • Skin delivery
  • Skin inflammation

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

van der Burg, Nicole M. D. ; Depelsenaire, Alexandra C. I. ; Crichton, Michael L. ; Kuo, Paula ; Phipps, Simon ; Kendall, Mark A. F. / A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin. In: Journal of Controlled Release. 2019 ; Vol. 302. pp. 190-200.
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A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin. / van der Burg, Nicole M. D.; Depelsenaire, Alexandra C. I.; Crichton, Michael L.; Kuo, Paula; Phipps, Simon; Kendall, Mark A. F.

In: Journal of Controlled Release, Vol. 302, 28.05.2019, p. 190-200.

Research output: Contribution to journalArticle

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T1 - A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin

AU - van der Burg, Nicole M. D.

AU - Depelsenaire, Alexandra C. I.

AU - Crichton, Michael L.

AU - Kuo, Paula

AU - Phipps, Simon

AU - Kendall, Mark A. F.

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