Browsing by Author "Turkmen, Omer"

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Artesunate Inhibits Melanoma Progression in Vitro Via Suppressing Stat3 Signaling Pathway
(Springer Heidelberg, 2021) Berkoz, Mehmet; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Krosniak, Miroslaw; Turkmen, Omer; Korkmaz, Duygu; Keskin, Siddik
Background Melanoma is a life-threatening cancer characterized with a potentially metastatic tumor of melanocytic origin. Improved methods or novel therapies are urgently needed to eliminate the development of metastases. Artesunate is a semi-synthetic derivative of artemisinin used for trarment of malaria and cancer. The purpose of this study was to investigate the anti-cancer effect of artesunate and the role on STAT3 signaling in A375 human melanoma cell line. Methods Melanoma cells were treated with artesunate at concentrations of 0-5 mu M for 24 and 48 h. The inhibition of cell viability, colony formation, migration, invasion, adhesion, percentage of apoptotic cells, and expressions of signal transducer and activator of transcription-3 (STAT3) and related proteins were examined. Results Artesunate inhibited cellular proliferation of cancer cells by induction of apoptosis at sub-toxic doses. Cells treated with artesunate showed an inhibition in adhesion to extracellular matrix substrate matrigel and type IV collagen. Artesunate treatment showed a decreased cellular migration, invasion, and colony formation in melanoma cells. Artesunate also inhibited STAT3 and Src activations and STAT3 related protein expressions; such as metalloproteinase 2 (MMP-2), MMP-9, Mcl-1, Bxl-xL, vascular endothelial growth factor (VEGF), and Twist. Moreover, overexpression of constitutively active STAT3 in A375 cells attenuated the anti-proliferative, apoptotic and anti-invasive effects of artesunate. Conclusion The results obtained from this study demonstrated that the anticancer activity of artesunate occurred via STAT3 pathway and its target proteins. Therefore, it can be suggested that artesunate may be an important candidate molecule in the treatment of melanoma.
Development and Characterization of Self-Assembling Sirolimus-Loaded Micelles as a Sublingual Delivery System
(Elsevier, 2022) Turkmen, Omer; Baloglu, Esra
The aim of this study was to develop self-assembling micelles of poorly water soluble potent immunosuppressant agent sirolimus (SRL) to enhance the solubility and mucosal permeability as stable aqueous formulations for sublingual administration. D-alpha-tocopheryl 1000 succinate (TPGS), soy phosphatidylcholine (SPC), and sodium cholate (NaC) were used to prepare the SRL-loaded micelles using the one-step self-assembly method. The mean hydrodynamic diameter of optimal micelles ranged from approximately 13 to 42 nm with low polydispersity index (PDI). The formulations possessed drug loading (DL) and drug encapsulation efficiency (EE) of around 18% and 99%, respectively. SPC caused an increase in mean hydrodynamic diameter and PDI of micelles, but no negative impact on DL and EE values was observed when used at concentrations of <= 25% (w/w) of amphiphiles. However, NaC caused a detrimental effect on the characteristics of micelles in every respect. Ex vivo permeation studies revealed that TPGS-based micelles without SPC were not able to enhance the permeation of SRL compared to the SRL solution through bovine sublingual mucosa. However, the incorporation of SPC into the micelles significantly increased the mucosal permeation of SRL compared to the SRL solution. The optimal formulations maintained their characteristics at 4 degrees C for at least 90 days. These results support the feasibility of SRL-loaded micelles as a sublingual delivery system.
Formulation and Evaluation of Fexofenadine Hydrochloride Orally Disintegrating Tablets for Pediatric Use
(Elsevier Science Bv, 2018) Turkmen, Omer; Senyigit, Zeynep Ay; Baloglu, Esra
Allergic rhinitis is a common disease in children which has considerable negative effects on the quality of life. Fexofenadine hydrochloride (FFH) is a second-generation oral antihistamine which has been widely perscribed for alleviating symptoms of AR in children. The aim of this study was to take the advantage of convenient direct compression method for preparation of Orally Disintegrating Tablets (ODTs) containing 30 mg FFH per tablet. Six ready-to-use commercial tablet excipients (F-Melt (R), Pearlitol (R) Flash, Pharmaburst (R) 500, Prosolv (R) Easytab SP, Ludiflash (R), Parteck (R) ODT (R)) were used for direct compression and suitability of these excipients were evaluated. ODTs could be successfully compressed with all the investigated excipients and all of the formulations exhibited acceptable crushing stregth, low friability and remarkably short disintegration time. The ODTs which were able to possess a disintegration time below 30 s were considered eligible for further studies. In vitro dissolution studies showed a complete release of the drug from ODTs made from Pharmaburst (R) 500 within 15 min. Short term stability results exhibited no significant change of the drug in tested formulations. In conclusion, FFH containing ODTs formulated with Pharmaburst (R) 500 were determined explicitly the most promising formulation when compressed at a force of 1000 kg.
Formulation and in Vitro Evaluation of Pramipexole Orally Disintegrating Tablets for Pediatric Restless Leg Syndrome
(Marmara Univ, 2023) Turkmen, Omer; Pozharani, Leyla Beba; Amel, Moein
In this study, orally disintegrating tablets (ODT) of pramipexole dihydrochloride monohydrate (PPX) was developed with direct compression method by using ready-to-use excipients Parteck (R) ODT, Pharmaburst (R) 500, Ludiflash (R), F-Melt (R), and Prosolv (R) Easytab SP for pediatric restless leg syndrome (RLS). The formulated ODTs were circular in shape with a total weight of around 100 mg, which was appropriate for pediatric use. In spite of very low content of the drug, content uniformity could be obtained successfully in accordance to the pharmacopoeial specification with a satisfactory mechanical strength in terms of hardness and friability. However, formulations based on Parteck (R) ODT and Ludiflash (R) could not achieve a disintegration time <30 s according to in vitro disintegration test, which was also supported by the simulated wetting test. The optimal ODTs based on Pharmaburst<(R)> 500, F-Melt (R) and Prosolv (R) Easytab SP were further evaluated for in vitro dissolution study. A very fast release of the drug was observed with these formulations that reached a peak value in 10 min., which was superior than that of the reference conventional tablet formulation of PPX. As a result, pediatric orally disintegrating tablets of PPX were successfully formulated with Pharmaburst (R) 500, F-Melt (R) and Prosolv (R) Easytab SP by using direct compression method with suitable characteristics, which can be further studied to use in pediatric RLS.
Investigation of the Impact of Antiparasitic Drug Moxidectin on the Rewarding Effects of Alcohol
(Aepress Sro, 2022) Ekici, Abdurrahman; Gurbuz, Esra; Berkoz, Mehmet; Turkmen, Omer; Basbugan, Yildiray; Yunusoglu, Oruc
Alcohol addiction or alcoholism constitutes a significant risk factor worldwide for morbidity and mortality. Moxidectin is a recently approved anthelmintic drug, which also activates the gamma-aminobutyric acid receptors. The objective of the present study was to examine the impact of moxidectin on rewarding effects of ethanol in the conditioned place preference (CPP) model in mice. In separate experiments, mice were administered intraperitoneal (i.p.) injections of moxidectin (5 or 10 mg/kg) before a) acquisition of alcohol-induced CPP, b) each extinction session, and c) alcohol-induced reinstatement of CPP. The present experiments provide consistent data about ethanol place preference in mice (2 g/kg, i.p.), with mice in all tests spending significantly more time on the ethanol-paired side. The acquisition of the CPP response to ethanol was prevented by the administration of moxidectin at a dose of 10 mg/kg. Additionally, moxidectin treatment accelerated the extinction of ethanol CPP when given repeatedly during the extinction phase. Ethanol-induced reinstatement of CPP following an extinction phase was inhibited by moxidectin. Ethanol alone and co-administration with moxidectin did not change locomotor activity and motor coordination. In conclusion, we suggest that moxidectin may be a promising therapeutic candidate for prevention of ethanol-induced addiction and relapse as well as detoxification.
Roe Protein Hydrolysate of Alburnus Tarichi Induces Apoptosis in Breast Cancer Mcf-7 and Mda-Mb Cells Through a Caspase-Dependent Pathway
(General Physiol and Biophysics, 2020) Berkoz, Mehmet; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Krosniak, Miroslaw; Turkmen, Omer; Yunusoglu, Oruc
The protein hydrolysates of fishes have been reported to be a potential source of many health benefits components for pharmaceutical or nutritional applications. The aim of this study is to examine the possible antiproliferative function of roe protein hydrolysates of Alburnus tarichi using enzymatic hydrolysis against breast cancer cells and explore its detailed mechanisms. In addition, we evaluated the effects of protein hydrolysate on the proliferation and apoptosis of two human breast cancer cell lines (MCF-7 and MDA-MB-231). The cultured cells were treated with protein hydrolysate at concentrations of 0-5 mu g/ml for 24 h and 48 h. Inhibition of cell proliferation, percentage of apoptotic cells, cell cycle distribution, morphological changes, DNA fragmentation, intracellular reactive oxygen species (ROS) production, and apoptotic protein levels were also examined. Decreases in proliferation of MCF-7 and MDA-MB-231 cells were observed after treatment with the protein hydrolysate in a dose-dependent manner. Distinct morphological changes, a typical pattern of fragmented DNA, and increased intracellular ROS production and apoptotic protein levels were observed in both cell lines after hydrolysate treatment (p < 0.05). The results suggested that the protein hydrolysate inhibits the proliferation of human breast cancer cell lines by introducing apoptosis through a caspase-dependent pathway in a dose-dependent manner.