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    Drug-impregnated contact lenses via supercritical carbon dioxide: A viable solution for the treatment of bacterial and fungal keratitis
    (Elsevier, 2024) Gungor, Buket; Erdogan, Hakika; Suner, Selin S.; Silan, Coskun; Saraydin, Serpil U.; Sahiner, Nurettin
    Keratitis is a corneal infection caused by various bacteria and fungi. Eye drop treatment of keratitis involves significant challenges due to difficulties in administration, inefficiencies in therapeutic dosage, and frequency of drug applications. All these are troublesome and result in unsuccessful treatment, high cost, time loss, development of drug resistance by microorganisms, and a massive burden on human health and the healthcare system. Most of the antibacterial and antifungal medications are non-water-soluble and/or include toxic drug formulations. Here, the aim was to develop drug-loaded contact lenses with therapeutic dosage formulations and extended drug release capability as an alternative to eye drops, by employing supercritical carbon dioxide (ScCO2) as a drug impregnation solvent to overcome inefficient ophthalmic drug use. ScCO2, known as a green solvent, has very low viscosity which provides high mass transfer power and could enhance drug penetration into contact lenses much better with respect to drug loading using other solvents. Here, moxifloxacin (MOX) antibiotic and amphotericin B (AMB) antifungal medicines were separately loaded into commercially available silicone hydrogel contact lenses through 1) drug adsorption from the aqueous solutions and 2) impregnation techniques via ScCO2 and their efficacies were compared. Drug impregnation parameters, i.e., 8-25 MPa pressure, 310-320 K temperature, 2-16-hour impregnation times, and the presence of ethanol as polar co-solvent were investigated for the optimization of the ScCO2 drug impregnation process. The highest drug loading and long-term release kinetic from the contact lenses were obtained at 25 MPa and 313 K with 2.5 h impregnation time by using 1 % ethanol (by volume). Furthermore, antibacterial/antifungal activities of the MOX- and AMBimpregnated contact lenses were effective against in vitro Pseudomonas aeruginosa (ATCC 10145) bacteria and Fusarium solani (ATCC 36031) fungus for up to one week. Consequently, the ScCO2 method can be effectively used to impregnate commercial contact lenses with drugs, and these can then be safely used for the treatment of keratitis. This offers a sustainable delivery system at effective dosage formulations with complete bacterial/ fungal inhibition and termination, making it viable for real animal/human applications.
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    Moxifloxacin-Impregnated Contact Lenses for Treatment of Keratitis in Rabbit Eyes
    (Wiley, 2025) Erdogan, Hakika; Gungor, Buket; Suner, Selin S.; Silan, Coskun; Saraydin, Serpil U.; Saraydin, Dursun; Ayyala, Ramesh S.
    Moxifloxacin (MOX) was loaded into commercial contact lenses (CLs) via supercritical carbon dioxide (ScCO2) to attain MOX-impregnated CL for keratitis treatment. This study aimed to investigate Pseudomonas keratitis treatment with MOX-impregnated CL compared to the traditional eyedrop administration. MOX impregnation was accomplished employing optimum parameters of 2.5 h drug exposure time, 25 MPa pressure, and 313 K for ScCO2 conditions using ethanol co-solvent rendering sustainable delivery, up to 7 days at effective dosage formulation. The MOX-impregnated CL was found to be safe with no significant toxicity on fibroblast cells after 5 days of contact time. Bacterial viability in vivo keratitis treatment in rabbit eyes was significantly decreased to 10(2) from 10(9) CFU/cornea for MOX-impregnated CL treatment, almost similar to exhaustive conventional 0.5% MOX eye drop treatments. The MOX-impregnated CL treatment revealed no conjunctival hyperemia, edema, or secretion for all eyes in the relevant group, and transparent cornea with no keratitis focus was obtained for two of the eyes (n = 6). The normal histological structure was seen with MOX-impregnated CL treatment on healthy eyes. Moreover, polymorphonuclear cell infiltration observed in keratitis eyes without any treatment was significantly decreased to a few polymorphonuclear cells in the groups treated with MOX eyedrops and MOX-impregnated CL.
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    The prevalence of VKORC1 1639 G > A and CYP2C9*2*3 genotypes in patients that requiring anticoagulant therapy in Turkish population
    (SPRINGER, 2012) Silan, Coskun; Dogan, Omer Tamer; Silan, Fatma; Kukulguven, Fatma Mutlu; Asgun, Halil Fatih; Ozdemir, Semra; Uludag, Ahmet; Atik, Sinem; Gungor, Buket; Akdur, Secil; Aksulu, Hakki Engin; Ozdemir, Ozturk
    The aim was to investigate the prevalence of VKORC1 and CYP2C9 genotypes in patients requiring anticoagulant therapy in two different region's populations of Turkey. The recent cohort included 292 patients that needed anticoagulant therapy, and who had a history of deep vein thrombosis and/or pulmonary artery thromboembolism. Genomic DNA was isolated from peripheral blood samples and the StripAssay reverse hybridization or Real Time PCR technique was used for genotype analysis. Genotypes for CYP2C9 were detected as follows: 165 (56.5 %) for CYP2C9*1/*1, 67 (23.0 %) for CYP2C9*1/*2, 25 (8.6 %) for CYP2C9*1/*3, 9 (3.0 %) for CYP2C9*2/*2, 21 (7.2 %) for CYP2C9*2/*3, 5(1.7 %) for CYP2C9*3/*3 for CYP2C9 and the allele frequencies were: 0.723 for allele*1, 0.182 for allele*2 and 0.095 for allele*3 respectively. Genotypes for VKORC1 were detected as follows: 64 (21.9 %) for GG, 220 (75.4 %) for GA and 8 (2.7 %) for AA alleles. The G allele frequency was detected as 0.596, and the A allele frequency was 0.404. The VKORC1 1639 G > A and CYP2C9 mutation prevalence and allele frequency of the current results from two different populations (Sivas and Canakkale) showed similarly very variable profiles when compared to the other results from the Turkish population.