Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery

Aaron Courtenay, Emma McAlister, Maeliosa T. C. McCrudden, Lalitkumar K. Vora, Lilach Steiner, Galit Levin, Etgar Levy-Nissenbaum, Nava Shterman, Mary-Carmel Kearney, Helen McCarthy, Ryan F. Donnelly

Research output: Contribution to journalArticle

3 Citations (Scopus)
1 Downloads (Pure)

Abstract

Treatment resistant depression is, by definition, difficult to treat using standard therapeutic interventions. Recently, esketamine has been shown as a viable rescue treatment option in patients in depressive crisis states. However, IV administration is associated with a number of drawbacks and advanced delivery platforms could provide an alternative parenteral route of esketamine dosing in patients. Hydrogel-forming microneedle arrays facilitate transdermal delivery of drugs by penetrating the outer layer of the skins surface, absorbing interstitial skin fluid and swelling. This subsequently facilitates permeation of medicines into the dermal microcirculation. This paper outlines the in vitro formulation development for hydrogel-forming microneedle arrays containing esketamine. Analytical methods for the detection and quantitation of esketamine were developed and validated according to International Conference on Harmonisation standards. Hydrogel-forming microneedle arrays were fully characterised for their mechanical strength and skin insertion properties. Furthermore, a series of esketamine containing polymeric films and lyophilised reservoirs were assessed as drug reservoir candidates. Dissolution testing and content drug recovery was carried out, followed by permeation studies using 350 µm thick neonatal porcine skin in modified Franz cell apparatus. Lead reservoir candidates were selected based on measured physicochemical properties and brought forward for testing in female Sprague-Dawley rats. Plasma samples were analysed using reverse phase high performance liquid chromatography for esketamine. Both polymeric film and lyophilised reservoirs candidate patches achieved esketamine plasma concentrations higher than the target concentration of 0.15 – 0.3 µg/ml over 24 h. Mean plasma concentrations in rats, 24 h post-application of microneedle patches with drug reservoir F3 and LW3, were 0.260 µg/ml and 0.498 µg/ml, respectively. This developmental study highlights the potential success of hydrogel-forming microneedle arrays as a transdermal drug delivery platform for ESK and supports moving to in vivo tests in a larger animal model.
Original languageEnglish
Pages (from-to)177-186
Number of pages10
JournalJournal of Controlled Release
Volume322
Early online date19 Mar 2020
DOIs
Publication statusPublished - 10 Jun 2020

Keywords

  • Esketamine
  • In vivo
  • Microneedle array
  • Treatment resistant depression

Fingerprint Dive into the research topics of 'Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery'. Together they form a unique fingerprint.

  • Cite this

    Courtenay, A., McAlister, E., McCrudden, M. T. C., Vora, L. K., Steiner, L., Levin, G., Levy-Nissenbaum, E., Shterman, N., Kearney, M-C., McCarthy, H., & Donnelly, R. F. (2020). Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery. Journal of Controlled Release, 322, 177-186. https://doi.org/10.1016/j.jconrel.2020.03.026