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

Autor: Robert Gurny, Francine Behar-Cohen, Doris Gabriel, Yogeshvar N. Kalia, Laura Kowalczuk, Tatiana Favez, Naoual Dahmana, Thibault Mugnier
Přispěvatelé: Université de Genève (UNIGE), Apidel SA, Fondation Asile des aveugles - Hôpital Ophtalmique Jules-Gonin [Lausanne], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Genève = University of Geneva (UNIGE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Gestionnaire, HAL Sorbonne Université 5
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Conceptualization
Writing -review & editing. Francine Behar-Cohen: Conceptualization
Pharmaceutical Science
Funding acquisition
02 engineering and technology
Spironolactone
Pharmacology
030226 pharmacology & pharmacy
chemistry.chemical_compound
0302 clinical medicine
Mineralocorticoid receptor
Methodology Doris Gabriel: Investigation
Tissue Distribution
Canrenone
Receptor
Micelles
Visualization
Chemistry
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
021001 nanoscience & nanotechnology
Resources
3. Good health
[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences
Writing -review & editing Robert Gurny: Conceptualization
medicine.anatomical_structure
[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs
0210 nano-technology
Glucocorticoid
medicine.drug
CRediT authorship contribution statement Naoual Dahmana: Conceptualization
Supervision
03 medical and health sciences
Dermis
Formal analysis
medicine
Humans
[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Glucocorticoids
Investigation
Wound Healing
Data curation
Writing -review & editing
Methodology
Conceptualization Tatiana Favez : Investigation
Writing -review & editing Yogeshvar N. Kalia: Conceptualization
Writing -original draft. Thibault Mugnier: Investigation
Receptors
Mineralocorticoid/metabolism
Acne
Androgen receptor antagonist
Cutaneous biodistribution
Follicular delivery
Immunofluorescence
Methoxy-poly(ethylene glycol)-di-hexyl-substituted-poly(lactic acid)
Wound healing
Receptors
Mineralocorticoid
Methodology Laura Kowalczuk: Investigation
Nanocarriers
Project administration
Zdroj: International Journal of Pharmaceutics
International Journal of Pharmaceutics, Elsevier, 2021, pp.120773. ⟨10.1016/j.ijpharm.2021.120773⟩
International Journal of Pharmaceutics, 2021, pp.120773. ⟨10.1016/j.ijpharm.2021.120773⟩
International journal of pharmaceutics, vol. 604, pp. 120773
ISSN: 0378-5173
Popis: 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.
Databáze: OpenAIRE
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