Nicole M.D. van der Burg*, Patrick G. Holt, Simon Phipps, Michael L. Crichton, Alexandra C.I. Depelsenaire, Mark A.F. Kendall

 

Bldg #75, Cnr College and Cooper Rds,
University of Queensland, St Lucia
Australian Institute for Bioengineering and Naotechnology
Brisbane, Queensland, Australia

 

Recent studies suggest that epidermal skin-targeted allergy immunotherapy (AIT) can resolve symptoms within months without a systemic reaction. However delivering a consistent dose to the epidermis layer, which is ~100 micons thick (in humans), has proven difficult. Common methods of epidermal delivery include painful tape stripping or lengthy topical absorption application (lasting days), neither of which are ideal for a repetitive treatment like AIT. Additionally, introducing inflammation to the delivery site (such as tape stripping) can activate an unwanted inflammatory response to the immunotherapy. While lacking any inflammation at the site can require AITs that last for years. Here we discuss our progress on a microprojection array (MPA) capable of quickly delivering AIT to the epidermis of mice (e.g. minutes) and detail its effect on local skin inflammation during allergic tolerance.

 

MPA projections were 120 µm tall and fabricated in an array of 7,000 projections/cm2. Using a shorter tolerance protocol (not AIT), mice were treated daily with different ovalbumin doses to activate tolerance then sensitised intraperitoneally and challenged via intranasal inhalation. Treatment administrations included intranasal inhalation, intradermal injection (i.d.) and epidermal MPA for no, low and increased skin inflammation respectively. Local skin inflammation and swelling was assessed by the number of cells killed during administration and by skin histology. Tolerance was assessed by eosinophil influx into bronchial alveolar lavage fluid and ova-specific IgE and IgG subtypes in sera.

The epidermal MPA (66% tolerance) required one tenth the dose (0.1 µg) of an i.d. (75% tolerance) and half the number of administrations, to achieve a similar tolerance percentage. To account for this large dose reduction, we hypothesised that local skin inflammation played a role in activating an ovalbumin-specific tolerance. Subsequently, epidermal MPAs induced 14 times more cell death at the delivery site than i.d.. Interestingly, epidermal MPAs with higher doses (> 1 µg) nor dermal MPAs (65 times cell death) induce allergic tolerance, suggesting a correlation between inflammation and tolerance in epidermal-based AIT.

Our work has shown the potential for quick and precise epidermal AIT whilst using smaller doses than previous technologies. The level of allergen and inflammation both appear important and this presentation will discuss how these may be translated into a practical device.

 

Biographic Details

Name: Nicole van der Burg

Title: Ms

Affiliation, Country: AIBN, UQ, Australia

Phone: 07 3346 4193 E-mail: nicole.vanderburg@uqconnect.edu.au

Research interests: Allergy and autoimmnity, immunotherapy, skin, microtechnology.

 

Venue

Room: 
Hawken N201