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

التفاصيل البيبلوغرافية
العنوان:	Polymeric micelle mediated follicular delivery of spironolactone: Targeting the mineralocorticoid receptor to prevent glucocorticoid-induced activation and delayed cutaneous wound healing.
المؤلفون:	Dahmana N; School of Pharmaceutical Sciences, University of Geneva, CMU - 1 rue Michel Servet, 1211 Geneva 4, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU - 1 rue Michel Servet, 1211 Geneva 4, Switzerland., Mugnier T; Apidel SA, 29 Quai du Mont Blanc, 1201 Geneva, Switzerland., Gabriel D; Apidel SA, 29 Quai du Mont Blanc, 1201 Geneva, Switzerland., Favez T; Fondation Asile des Aveugles - Hôpital Ophtalmique Jules-Gonin, 15 Avenue de France, 1004 Lausanne, Switzerland., Kowalczuk L; Fondation Asile des Aveugles - Hôpital Ophtalmique Jules-Gonin, 15 Avenue de France, 1004 Lausanne, Switzerland., Behar-Cohen F; Fondation Asile des Aveugles - Hôpital Ophtalmique Jules-Gonin, 15 Avenue de France, 1004 Lausanne, Switzerland; INSERM, UMRS 872 Team 17, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France., Gurny R; School of Pharmaceutical Sciences, University of Geneva, CMU - 1 rue Michel Servet, 1211 Geneva 4, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU - 1 rue Michel Servet, 1211 Geneva 4, Switzerland; Apidel SA, 29 Quai du Mont Blanc, 1201 Geneva, Switzerland., Kalia YN; School of Pharmaceutical Sciences, University of Geneva, CMU - 1 rue Michel Servet, 1211 Geneva 4, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU - 1 rue Michel Servet, 1211 Geneva 4, Switzerland. Electronic address: Yogi.Kalia@unige.ch.
المصدر:	International journal of pharmaceutics [Int J Pharm] 2021 Jul 15; Vol. 604, pp. 120773. Date of Electronic Publication: 2021 Jun 04.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7804127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3476 (Electronic) Linking ISSN: 03785173 NLM ISO Abbreviation: Int J Pharm Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
مواضيع طبية MeSH:	Micelles* , Spironolactone*, Glucocorticoids ; Humans ; Receptors, Mineralocorticoid/metabolism ; Tissue Distribution ; Wound Healing
مستخلص:	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 ² vs. 0.10 ± 0.03 ng/mm ² , 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. (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة:	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
المشرفين على المادة:	0 (Glucocorticoids) 0 (Micelles) 0 (Receptors, Mineralocorticoid) 27O7W4T232 (Spironolactone)
تواريخ الأحداث:	Date Created: 20210606 Date Completed: 20210727 Latest Revision: 20210727
رمز التحديث:	20240628
DOI:	10.1016/j.ijpharm.2021.120773
PMID:	34090990
قاعدة البيانات:	MEDLINE

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تدمد:	1873-3476
DOI:	10.1016/j.ijpharm.2021.120773