Phloretin microneedle patches applied on human psoriatic reconstructed skin

Summary: Abstract Body: Problem: Plaque psoriasis causes scaly inflamed lesions and epidermal thickening. Patients frequently require lifelong medication, increasing the risk of toxicity from systemic and biological therapies. Topical treatments are therefore prioritized, but their daily prescriptions can limit therapeutic adherence. Detachable and biodegradable microneedle (MN) skin patches could be the key. Phloretin, an antiproliferative and anti-inflammatory polyphenol, was incorporated into the MNs to assess their effect in human psoriatic reconstructed skin. Objectives: 1) Evaluate methods of applying MN patches on human reconstructed skin to maximize MN implantation. 2) Analyze the cutaneous diffusion of a fluorophore incorporated into MNs over two weeks of implantation in the skin. 3) Study the anti-psoriatic effect of these MN patches loaded with phloretin and applied on human psoriatic reconstructed skin, by measuring the epidermal thickness. Methodology: 1) MN patches loaded with a fluorophore, Cy5-COOH, were applied on reconstructed skin, then detached, leaving the MNs in the skin. The percentage of implanted MNs was determined by fluorescence imaging. 2) The diffusion of Cy5-COOH in the skin and culture supernatants were analyzed over 2 weeks. 3) Phloretin or methotrexate (psoriasis reference treatment) patches were applied to psoriatic substitutes for one week and compared with the molecules added to the culture medium. The epidermal thickness was compared. Results: 1) 91.5% of the microneedles remained implanted in the reconstructed skin. 2) Up to 105 pg/mL of Cy5-COOH were quantified in the culture supernatants after 5 days, indicating diffusion to the dermis. 3) Epidermal thickness of the skin near the patches was reduced by 37.33% with phloretin patches. Conclusion: Microneedle patches loaded with phloretin are promising for psoriasis. Yasmine Ruel^{1, 2}, Fatma Moawad³, Davide Brambilla³, Roxane Pouliot^{1, 2} 1. Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Centre de Recherche du CHU de Québec-Université Laval, Quebec, QC, Canada. 2. Universite Laval Faculte de Pharmacie, Québec City, QC, Canada. 3. Universite de Montreal Faculte de Pharmacie, Montreal, QC, Canada. Translational Studies: Preclinical