title: Enhanced effect in combination of curcumin- and ketoconazole-loaded methoxy poly (ethylene glycol)-poly (ε-caprolactone) micelles.
abstract: In order to enhance water-solubility and realize controlled release while keeping synergistic effects of ketoconazole and curcumin, drug-loaded methoxy poly (ethylene glycol)-b-poly (ε-caprolactone) micelles were prepared through thin membrane hydration method. Transmission electric microscopy and dynamitic light scattering characterization revealed the formation of ketoconazole- and curcumin-loaded micelles with an average size of 44.70nm and 39.56nm, respectively. The drug-loaded micelles endowed the two drugs' slow controlled release with water-solubility enhanced to 85 and 82000 folds higher than the corresponding raw drugs, respectively. In vitro antifungal activity test, chequerboard test and inhibition zone test indicated that efficacy of ketoconazole-loaded micelles was improved by introduction of curcumin-loaded micelles with a low fractional inhibitory concentration index (0.073). Biofilm formation inhibition assay also demonstrated that participation of curcumin-loaded micelles obviously strengthened the inhibition of fungal biofilms formation induced by ketoconazole-loaded micelles. The high synergistic activity of combinations is encouraging and the MPEG-PCL micelle is a potential drug delivery system for the combination of ketoconazole and curcumin.
authors.affiliation: School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, No. l6866 East Road of Jingshi, Jinan 250200, Shandong Province, PR China; Shandong Academy of Medical Sciences, No. 18877 Jingshi Road, Jinan 250062, Shandong Province, PR China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Teng
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China.
authors.forename: Peizong
authors.initials: P
authors.lastname: Deng
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Song
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China.
authors.forename: Feilong
authors.initials: F
authors.lastname: Zhou
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China. Electronic address: runliangfeng@126.com.
authors.forename: Runliang
authors.initials: R
authors.lastname: Feng
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005026:Ethylene Glycols / Q000737:chemistry*; D007654:Ketoconazole / Q000494:pharmacology*; D008823:Micelles; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D011091:Polyesters / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared
chemical_list: D000935:Antifungal Agents; D005026:Ethylene Glycols; D008823:Micelles; D011091:Polyesters; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D003474:Curcumin; D007654:Ketoconazole
keywords: Curcumin; Ketoconazole; MPEG-PCL; Micelles; Synergistic effect