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    Development of effective AmB/AmB-?CD complex double loaded liposomes using a factorial design for systemic fungal infection treatment
    (Taylor & Francis Ltd, 2021) Mutlu-Agardan, N. Basaran; Yilmaz, Sukran; Kaynak Onurdag, Fatma; Celebi, Nevin
    Amphotericin B (AmB) is a very potent antibiotic which still remains as the gold standard for the treatment of systemic fungal infections. AmB is a member of Biopharmaceutical Classification System Class IV, mainly characterized by its poor solubility and low permeability. In this study, AmB/AmB-alpha cyclodextrin complex double loaded liposomes (DLLs) were developed using the design of experiments (DoE (R)) approach to optimize/determine the effects of lipid composition and other parameters on final product properties such as encapsulation efficacy, particle size, polydispersity index, and zeta potential. Experimental design 2(4) was used for optimization of these properties in which four factors were studied in two levels. DLLs showed much higher physical stability than liposomes loaded only with free AmB by the means of particle size, zeta potential and encapsulation efficiency, in addition exhibited sustained release of AmB over 72 h (26.7%) with faster onset time. On the other hand, fourfold improved antimicrobial efficiency, minimum inhibitory concentration (0.125 mu g/ml), and minimum fungicidal concentration (0.5 mu g/ml) was determined by DLLs against C. albicans compared to Ambisome. Dose dependent effects of the DLLs were investigated by cytotoxicity studies on Vero and L-929 cells. No significant cytotoxicity observed for AmB/AmB-alpha CD complex DLLs and Ambisome at tested concentrations while free AmB caused severe cytotoxicity. Lastly the developed DLLs did not cause an increase in NGAL (an early biomarker for acute kidney toxicity) levels for both Vero and HK-2 cell lines compared to free AmB.
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    Investigation of Antimicrobial and Antibiofilm Effects of Some Preservatives Used in Drugs, Cosmetics and Food Products
    (Ankara Microbiology Soc, 2014) Guven, Nihal; Kaynak Onurdag, Fatma
    Preservatives are added to food, drugs and other pharmaceutical products to avoid microbial contamination. For antimicrobial activity testing and preservative efficacy testing, vegetative forms of the standard test organisms are used. However, microbial biofilm formation may occur on living tissues, medical implants, industrial or drinking water pipes, natural aquatic systems, glass and plastic surfaces. In our study, it was aimed to determine the antimicrobial and antibiofilm effects of some preservatives used in drug, cosmetics and food products and to compare the minimum biofilm inhibitory concentration (MBIC) of microbial biofilm formed on glass surfaces which are commonly used in those areas and the minimum inhibitory concentration (MIC) values of the planktonic forms. In the study Pseudomonas aeruginosa ATCC 27853, Salmonella Thyphimurium SL1344, Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis NCTC 11047, Enterococcus faecalis ATCC 29212 and Candida albicans ATCC 10231 were used as the standard strains; sodium nitrate, methylparaben, prophylparaben, potassium sorbate and sodium benzoate as the preservatives; ampicillin, vancomycin, gentamicin, ciprofloxacin, amphotericin B and itraconazole as the antimicrobial agents. MIC values were determined through the guidelines of CLSI M100-S18 and M27-A3 protocols. BioTimer method was used to determine the MBIC values. The value of colony forming unit (CFU)/glass beads was calculated using the graphics drawn by plotting the time of color change for phenol red or resazurin against log(10)CFU. All experiments were done with four media at different pH values namely pH: 7, pH: 6.5, pH: 6 and pH: 5.5. According to the results of tests on planktonic forms of the microorganisms, sodium benzoate was determined to be the most effective preservative against all the microorganisms tested except S.aureus and E.faecalis. The most effective preservative against S.aureus and E.faecalis was prophylparaben. Prophylparaben was also effective against S.epidermidis. However, in our study it was determined that preservatives were not effective against biofilm forms even if the inoculum was lower, equal to or higher than the inocula of the planktonic forms. The data obtained from this study indicated that preservatives used to prevent microbial contamination in pharmaceutical, cosmetic and food products, are not effective against biofilm forms of the microorganisms. This study is thought to be a guide for further studies to be held in the investigation of antimicrobial and antibiofilm effects of preservatives used in drugs, cosmetics and food industry.
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    SYNTHESIS AND ANTITUBERCULAR ACTIVITY OF OFLOXACIN DERIVATIVES
    (Editura Acad Romane, 2018) Dundar, Yasemin; Ulger, Mahmut; Kaynak Onurdag, Fatma; Okten, Suzan; Onkol, Tijen
    A series of novel ofloxacin derivatives were prepared and screened for their antimycobacterial activity. Among the synthesized compounds, 2, 3, 18, 19, 26 exhibited significant antimycobacterial activity. Additionally, all synthesized compounds were evaluated for their antibacterial and antifungal activity.