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

doi:10.1016/j.jconrel.2019.03.027

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

J Control Release. 2019 May 28:302:190-200. doi: 10.1016/j.jconrel.2019.03.027. Epub 2019 Mar 30.

Authors

Nicole M D van der Burg¹, Alexandra C I Depelsenaire¹, Michael L Crichton¹, Paula Kuo², Simon Phipps³, Mark A F Kendall⁴

Affiliations

¹ The Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St. Lucia, QL 4072, Australia.
² The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, QL 4102, Australia.
³ QIMR Berghofer Medical Research Institute, Herston, QL 4006, Australia.
⁴ The Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St. Lucia, QL 4072, Australia; The Australian National University, Canberra, Australian Capital Territory 2600, Australia. Electronic address: Mark.Kendall@anu.edu.au.

PMID: 30940498
DOI: 10.1016/j.jconrel.2019.03.027

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.

Keywords: Epidermis; Langerhans cell targeting; Microneedle; Microprojection; Skin delivery; Skin inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement
Cell Survival / drug effects
Dermis / chemistry*
Drug Carriers / chemistry*
Drug Liberation
Epidermal Cells / drug effects
Epidermis / drug effects*
Inflammation / prevention & control*
Langerhans Cells / metabolism*
Mice
Mice, Inbred BALB C
Models, Theoretical
Ovalbumin / administration & dosage
Ovalbumin / chemistry*
Polycarboxylate Cement / chemistry
Silicon / chemistry
Skin
Transdermal Patch

Substances

Drug Carriers
Polycarboxylate Cement
polycarbonate
Ovalbumin
Silicon