Polymeric Micelle Mediated Follicular Delivery of Spironolactone: Targeting the Mineralocorticoid Receptor to Prevent Glucocorticoid-Induced Activation and Delayed Cutaneous Wound Healing

    Naoual Dahmana, Thibault Mugnier, Doris Gabriel, Tatiana Favez, Laura Kowalczuk, Francine Béhar-Cohen, Robert Gurny, Yogeshvar N. Kalia
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    TLDR Using polymeric micelles to deliver spironolactone topically could improve wound healing in skin affected by glucocorticoids.
    The study explored the use of polymeric micelles to deliver spironolactone (SPL) topically to improve wound healing in skin affected by glucocorticoids, which can delay healing by activating mineralocorticoid receptors (MR). SPL, a potent MR antagonist, was encapsulated in nanomicelles to enhance its solubility. The SPL-loaded nanomicelles targeted the pilosebaceous unit (PSU) in porcine skin, delivering 5-fold higher SPL levels in PSU-containing biopsies compared to PSU-free skin. This targeted delivery was confirmed through immunofluorescence, which showed MRs were mainly located in the PSU. The study also found that the SPL nanomicellar solution and hydrogel were stable and suitable for topical application, with the hydrogel delivering greater amounts of SPL to the upper dermis under infinite dose conditions. The presence of the active metabolite canrenone (CAN) in the skin indicated effective MR antagonism. No transdermal permeation was observed, suggesting low systemic concentrations upon in vivo application. The study did not specify the number of subjects involved.
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