A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin
van der Burg, Nicole M.D. LU
; Depelsenaire, Alexandra C.I.
; Crichton, Michael L.
; Kuo, Paula
; Phipps, Simon
and Kendall, Mark A.F.
(2019)
In Journal of Controlled Release
302.
p.190-200
- 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,... (More)
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.
(Less)
- author
- van der Burg, Nicole M.D.
LU
; Depelsenaire, Alexandra C.I.
; Crichton, Michael L.
; Kuo, Paula
; Phipps, Simon
and Kendall, Mark A.F.
- publishing date
- 2019-05-28
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Epidermis, Langerhans cell targeting, Microneedle, Microprojection, Skin delivery, Skin inflammation
- in
- Journal of Controlled Release
- volume
- 302
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:85064871026
- pmid:30940498
- ISSN
- 0168-3659
- DOI
- 10.1016/j.jconrel.2019.03.027
- language
- English
- LU publication?
- no
- id
- 6a604612-05c0-41a9-aeb2-2e1470b6e9d9
- date added to LUP
- 2020-11-30 12:21:09
- date last changed
- 2024-05-02 22:09:55
@article{6a604612-05c0-41a9-aeb2-2e1470b6e9d9,
abstract = {{<p>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.</p>}},
author = {{van der Burg, Nicole M.D. and Depelsenaire, Alexandra C.I. and Crichton, Michael L. and Kuo, Paula and Phipps, Simon and Kendall, Mark A.F.}},
issn = {{0168-3659}},
keywords = {{Epidermis; Langerhans cell targeting; Microneedle; Microprojection; Skin delivery; Skin inflammation}},
language = {{eng}},
month = {{05}},
pages = {{190--200}},
publisher = {{Elsevier}},
series = {{Journal of Controlled Release}},
title = {{A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin}},
url = {{http://dx.doi.org/10.1016/j.jconrel.2019.03.027}},
doi = {{10.1016/j.jconrel.2019.03.027}},
volume = {{302}},
year = {{2019}},
}