Antimycotic influence of beta-cyclodextrin complexes--in vitro measurements using laser nephelometry in microtiter plates.

To determine the in vitro susceptibility of fungal organisms to beta-cyclodextrin (CD) complexes with the antifungal agents econazole-nitrate (EC) and ciclopirox-olamine (CI), a fast, rapid and simple method using laser nephelometry in 96-microtiter plate is used. The antimycotic influence of the complexes against Candida albicans DSM 11225 and Candida krusei ATCC 6258 species was determined using this method. A rapid inhibition and even killing of both fungi was observed only above certain concentrations of complex ranged between 12.5 and 100 microg/ml for beta-CD-econazole complex (CD-EC), while for the complex with ciclopirox-olamine (CD-CI) the range was between 150 and 400 microg/ml. The stability constants of the CD complexes with the two antimycotic derivatives are given. In addition, the nephelometric method allows the determination of solubilities of active agents. Thus, the improvement of solubility of both antimycotic agents in PBS buffer solution was observed by complexation with CD.

[1]  R. Haugland,et al.  Development of the FUN-1 family of fluorescent probes for vacuole labeling and viability testing of yeasts , 1997, Applied and environmental microbiology.

[2]  Th. Ackermann,et al.  K. A. Connors: Binding constants — the measurement of molecular complex stability, John Wiley & Sons, New York, Chichester, Brisbane, Toronto, Singapore 1987. 411 Seiten, Preis: £ 64.15 , 1987 .

[3]  F. Greenwood,et al.  THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. , 1963, The Biochemical journal.

[4]  A. Scarpellini,et al.  Formation and antimycotic effect of cyclodextrin inclusion complexes of econazole and miconazole , 1993 .

[5]  M. Ghannoum,et al.  Evaluation of in vitro activity of ciclopirox olamine, butenafine HCl and econazole nitrate against dermatophytes, yeasts and bacteria , 2003, International journal of dermatology.

[6]  T. Hoehler,et al.  Ciclopirox olamine: a hydroxypyridone antifungal agent. , 1991, Clinics in dermatology.

[7]  M. Brewster,et al.  Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. , 1996, Journal of pharmaceutical sciences.

[8]  K. A. Connors,et al.  Binding Constants: The Measurement of Molecular Complex Stability , 1987 .

[9]  M. Ghannoum,et al.  Voriconazole (UK-109,496) inhibits the growth and alters the morphology of fluconazole-susceptible and -resistant Candida species , 1997, Antimicrobial agents and chemotherapy.

[10]  Gerd Folkers,et al.  Pharmacokinetic optimization in drug research , 2001 .

[11]  D. Barber,et al.  A logical stepwise approach to laser diffraction particle size distribution analysis methods development and validation. , 1998, Pharmaceutical development and technology.

[12]  S. Costa-de-Oliveira,et al.  Susceptibility to fluconazole of Candida clinical isolates determined by FUN-1 staining with flow cytometry and epifluorescence microscopy. , 2001, Journal of medical microbiology.

[13]  S. López-Gómez,et al.  Changes in fungal ultrastructure after short‐course ciclopiroxolamine therapy in pityriasis versicolor , 1990, Clinical and experimental dermatology.

[14]  M. Ghannoum,et al.  Comparison of Biofilms Formed by Candidaalbicans and Candidaparapsilosis on Bioprosthetic Surfaces , 2002, Infection and Immunity.

[15]  Aditya K. Gupta,et al.  Ciclopirox: an overview , 2001, International journal of dermatology.

[16]  H. Korting,et al.  The hydroxypyridones: a class of antimycotics of its own , 1997, Mycoses.

[17]  Sanjeev Jain,et al.  Itraconazole: an effective oral antifungal for onychomycosis , 2001, International journal of dermatology.

[18]  P. Mura,et al.  Improvement of dissolution properties and microbiological activity of miconazole and econazole by cyclodextrin complexation , 1992 .

[19]  S. Ahmed,et al.  Effect of cyclodextrins on the physicochemical properties and antimycotic activity of clotrimazole , 1998 .

[20]  M. Másson,et al.  Methods to enhance the complexation efficiency of cyclodextrins , 1999 .

[21]  C. Bevan,et al.  A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates. , 2000, Analytical chemistry.

[22]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings , 1997 .

[23]  J. Cope Mode of action of miconazole on Candida albicans: effect on growth, viability and K+ release. , 1980, Journal of general microbiology.