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  4. Novel micelle formulations to increase cutaneous bioavailability of azole antifungals.
 
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Titre

Novel micelle formulations to increase cutaneous bioavailability of azole antifungals.

Type
article
Institution
Externe
Périodique
Journal of Controlled Release  
Auteur(s)
Bachhav, Y.G.
Auteure/Auteur
Mondon, K.
Auteure/Auteur
Kalia, Y.N.
Auteure/Auteur
Gurny, R.
Auteure/Auteur
Möller, M.
Auteure/Auteur
Liens vers les personnes
Möller, Mathias  
ISSN
1873-4995
Statut éditorial
Publié
Date de publication
2011
Volume
153
Numéro
2
Première page
126
Dernière page/numéro d’article
132
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Efficient topical drug administration for the treatment of superficial fungal infections would deliver the therapeutic agent to the target compartment and reduce the risk of systemic side effects. However, the physicochemical properties of the commonly used azole antifungals make their formulation a considerable challenge. The objective of the present investigation was to develop aqueous micelle solutions of clotrimazole (CLZ), econazole nitrate (ECZ) and fluconazole (FLZ) using novel amphiphilic methoxy-poly(ethylene glycol)-hexyl substituted polylactide (MPEG-hexPLA) block copolymers. The CLZ, ECZ and FLZ formulations were characterized with respect to drug loading and micelle size. The optimal drug formulation was selected for skin transport studies that were performed using full thickness porcine and human skin. Penetration pathways and micellar distribution in the skin were visualized using fluorescein loaded micelles and confocal laser scanning microscopy. The hydrodynamic diameters of the azole loaded micelles were between 70 and 165nm and the corresponding number weighted diameters (d(n)) were 30 to 40nm. Somewhat surprisingly, the lowest loading efficiency (<20%) was observed for CLZ (the most hydrophobic of the three azoles tested); in contrast, under the same conditions, ECZ was incorporated with an efficiency of 98.3% in MPEG-dihexPLA micelles. Based on the characterization data and preliminary transport experiments, ECZ loaded MPEG-dihexPLA micelles (concentration 1.3mg/mL; d(n)<40nm) were selected for further study. ECZ delivery was compared to that from Pevaryl® cream (1% w/w ECZ), a marketed liposomal formulation for topical application. ECZ deposition in porcine skin following 6h application using the MPEG-dihexPLA micelles was >13-fold higher than that from Pevaryl® cream (22.8±3.8 and 1.7±0.6μg/cm(2), respectively). A significant enhancement was also observed with human skin; the amounts of ECZ deposited were 11.3±1.6 and 1.5±0.4μg/cm(2), respectively (i.e., a 7.5-fold improvement in delivery). Confocal laser scanning microscopy images supported the hypothesis that the higher delivery observed in porcine skin was due to a larger contribution of the follicular penetration pathway. In conclusion, the significant increase in ECZ skin deposition achieved using the MPEG-dihexPLA micelles demonstrates their ability to improve cutaneous drug bioavailability; this may translate into improved clinical efficacy in vivo. Moreover, these micelle systems may also enable targeting of the hair follicle and this will be investigated in future studies.
PID Serval
serval:BIB_11205EA0B495
DOI
10.1016/j.jconrel.2011.03.003
PMID
21397643
WOS
000293312900004
Permalien
https://iris.unil.ch/handle/iris/112678
Date de création
2011-08-23T10:52:23.854Z
Date de création dans IRIS
2025-05-20T19:30:12Z
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