Enhancing intradermal delivery of tofacitinib citrate: Comparison between powder-loaded hollow microneedle arrays and dissolving microneedle arrays

Álvaro Cárcamo-Martínez, Brónach Mallon, Qonita Kurnia Anjani, Juan Domínguez-Robles, Emilia Utomo, Lalit K. Vora, Ismael A. Tekko, Eneko Larrañeta, Ryan F. Donnelly

Research output: Contribution to journalArticlepeer-review

Abstract

Autoimmune-mediated inflammatory skin diseases, such as psoriasis, alopecia areata, and vitiligo, have been reported as the 4th leading cause of nonfatal disease burden worldwide. This is mainly related to the poor quality of life experienced by these patients. Although topical and systemic steroids represent the most common treatment, the variability in success rates and side effects often lead to treatment discontinuation. Recent off-label clinical studies using oral Janus Kinase (JAK) inhibitors (e.g., ruxolitinib, tofacitinib, baraticinib) have shown promising results. However, frequent side effects, such as infections and blood clots have been reported. Therefore, the aim of this research was to enhance the intradermal delivery of tofacitinib citrate with MN arrays. Using crosslinked hydrogels containing modifying agents (urea, sorbitol and sodium chloride), hollow MN arrays were fabricated and then loaded with tofacitinib citrate. Their efficiency in intradermal delivery of tofacitinib was compared with dissolving MN arrays and a control (Aqueous cream BP), using neonatal porcine skin. Despite the fact that the hydrogel was only present on the outer surface, hollow MN arrays showed comparable resistance to compression values and insertion capabilities to dissolving MN arrays. Although hollow MN arrays containing NaCl in the formulation led to slightly higher depositions of tofacitinib in epidermis and dermis of neonatal porcine skin when compared to a control cream, dissolving MN arrays showed superiority in terms of tofacitinib deposition in the dermis. Indeed, at 24 h of the study, control cream and dissolving MN arrays delivered 143.98 ug/cm2 and 835 ug/cm2 of drug in the dermis, respectively, confirming the enhanced intradermal drug delivery capacity of MN arrays and their potential for treatment of autoimmune skin diseases.
Original languageEnglish
Article number120152
Number of pages14
JournalInternational Journal of Pharmaceutics
Volume593
Early online date07 Dec 2020
DOIs
Publication statusPublished - 25 Jan 2021

Keywords

  • Hollow microneedles
  • Dissolving microneedles
  • Hydrogel
  • Tofacitinib
  • Intradermal delivery
  • Autoimmune skin conditions

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