Polymeric micelle mediated follicular delivery of spironolactone: Targeting the mineralocorticoid receptor to prevent glucocorticoid-induced activation and delayed cutaneous wound healing.

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_AD1EA3AD275D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Polymeric micelle mediated follicular delivery of spironolactone: Targeting the mineralocorticoid receptor to prevent glucocorticoid-induced activation and delayed cutaneous wound healing.
Journal
International journal of pharmaceutics
Author(s)
Dahmana N., Mugnier T., Gabriel D., Favez T., Kowalczuk L., Behar-Cohen F., Gurny R., Kalia Y.N.
ISSN
1873-3476 (Electronic)
ISSN-L
0378-5173
Publication state
Published
Issued date
04/06/2021
Peer-reviewed
Oui
Volume
604
Pages
120773
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Impaired wound healing in patients receiving glucocorticoid therapy is a serious clinical concern: mineralocorticoid receptor (MR) antagonists can counter glucocorticoid-induced off-target activation of MR receptors. The aim of this study was to investigate the cutaneous delivery of the potent MR antagonist, spironolactone (SPL), from polymeric micelle nanocarriers, prepared using a biodegradable copolymer, methoxy-poly(ethylene glycol)-di-hexyl-substituted-poly(lactic acid). Immunofluorescent labelling of the MR showed that it was principally located in the pilosebaceous unit (PSU), justifying the study rationale since polymeric micelles accumulate preferentially in appendageal structures. Cutaneous biodistribution studies under infinite and finite dose conditions, demonstrated delivery of pharmacologically relevant amounts of SPL to the epidermis and upper dermis. Preferential PSU targeting was confirmed by comparing amounts of SPL in PSU-containing and PSU-free skin biopsies: SPL nanomicelles showed 5-fold higher delivery of SPL in the PSU-containing biopsies, 0.54 ± 0.18 ng/mm <sup>2</sup> vs. 0.10 ± 0.03 ng/mm <sup>2</sup> , after application of a hydrogel in finite conditions. Canrenone, an active metabolite of SPL, was also quantified in skin samples. In addition to being used for the treatment of delayed cutaneous wound healing by site-specific antagonism of the MR, the formulation might also be used to treat pilosebaceous androgen-related skin diseases, e.g. acne vulgaris, since SPL is a potent androgen receptor antagonist.
Keywords
Acne, Androgen receptor antagonist, Cutaneous biodistribution, Follicular delivery, Immunofluorescence, Methoxy-poly(ethylene glycol)-di-hexyl-substituted-poly(lactic acid), Micelles, Mineralocorticoid receptor, Spironolactone, Wound healing
Pubmed
Open Access
Yes
Create date
15/06/2021 16:03
Last modification date
19/06/2021 7:12
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