title: Poly(ethylene glycol)-block-poly(ε-caprolactone) nanomicelles for the solubilization and enhancement of antifungal activity of sertaconazole.
abstract: Sertaconazole nitrate is a broad spectrum imidazole antifungal agent with antibacterial and anti-inflammatory properties. However, its lipophilic nature and very poor aqueous solubility limit its use in the clinic. The aim of this study was to develop and characterize poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) polymeric nanomicelles for the solubilization and enhancement of sertaconazole antifungal activity. Sertaconazole was incorporated into PEG-b- PCL polymeric nanomicelles by a co-solvent evaporation method and micelle size, drug loading capacity and drug release properties were determined. The antifungal properties of nanomicelle-loaded drug were evaluated in Fusarium miscanthi, Microsporum canis, and Trichophyton mentagrophytes isolated, respectively from fungal keratitis, ringworm, and tinea corporis. PEG-b-PCL formed nanomicelles in aqueous solution with a diameter ranging from 40-80 nm, depending on the polymer composition and level of drug loading. Drug loading properties of the nanomicelles were dependent on the PCL block molecular weight and drug/polymer weight feed ratio. Drug encapsulation efficiency of up to 85% was achieved and this resulted in more than 80-fold enhancement in sertaconazole aqueous solubility at polymer concentration of 0.2%. Drug release studies showed an initial burst release followed by sustained drug release for 72 hours. In vitro antimycotic studies showed that nanomicelle-incorporated sertaconazole inhibited fungal growth in a concentration dependent manner. Further, it was more effective than the free drug in inhibiting the growth of Fusarium miscanthi and Microsporum canis. These results confirm the utility of PEG-b-PCL nanomicelles in enhancing the aqueous solubility and antifungal activity of sertaconazole or other similar antifungal drugs.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
authors.forename: Ghareb M
authors.initials: GM
authors.lastname: Soliman
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Attia
authors.forename: Ramadan A
authors.initials: RA
authors.lastname: Mohamed
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D005670:Fusarium / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D008823:Micelles; D008826:Microbial Sensitivity Tests; D008864:Microsporum / Q000187:drug effects; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D014249:Trichophyton / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D005026:Ethylene Glycols; D007093:Imidazoles; D008823:Micelles; D011091:Polyesters; D013876:Thiophenes; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); C061131:sertaconazole