Araştırmacılar(7)

• Aykaç, Kadir
• Haidar, Mohammad Karim
• Haydar, Muhammet Kerim
• Ozdal, Zeliha Duygu
• Pezik, Esra
• Polat, Heybet Kerem
• Polat, Kerem Heybet

• ArticleYalnız künye2026/r/ebyu/11446
  Development and characterization of olopatadine and verbascoside-loaded thermoresponsive in situ gels for ocular drug delivery: a factorial design approach for allergic conjunctivitis

  Polat, Heybet Kerem; Çopur, Tuğba; Pezik, Esra; Turanlı, Yasin; Karakuyu, Nasıf Fatih; Köngül, Esra; Ünal, Sedat; Gözcü, Sefa; Sarman, Emine

  Objective: Allergic conjunctivitis is one of the most prevalent conditions affecting the eyes, and various medications are used in its treatment. In this study, olopatadine and verbascoside were used in combination. Methods: A factorial design was employed to evaluate the effects of Poloxamer 407 and sodium alginate. The impact of polymer concentration on parameters such as viscosity, gelation time, mucoadhesion, pH, and gelation temperature–considered indicators of ideal formulations–was assessed. Results: The optimal formulation, determined through the factorial design, included 0.5% sodium alginate and 20% poloxamer 407. The obtained values were viscosity at 25 °C = 7451.8 cP, viscosity at 35 °C = 11367.3 cP, pH = 7.12, gelation temperature = 30 °C, gelation time = 52 s, and mucoadhesion = 0.301 N. Cytotoxicity tests on ARPE-19 and L929 cells, along with irritation studies, indicated acceptable safety profiles. In vitro release tests demonstrated an initial burst release of verbascoside and olopatadine during the first 2 h, followed by a controlled release over the subsequent 8 h. Mathematical analysis of the release kinetics revealed a good fit with the Weibull model. No adverse effects were observed in rats during Draize’s in vivo test. Conclusions: Consequently, the drug-loaded in situ gel formulation may be a promising option for treating allergic conjunctivitis.

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• ArticleYayıncıda açık erişim2026/r/ebyu/11416
  Formulation, Characterization, and Preliminary In Vitro Evaluation of Letrozole Incorporated Eudragit® RS 100 Nanoparticles Using HepG2 Cells

  Polat, Muhammet Ali; Aykaç, Kadir; Cantürk, Zerrin; Başaran, Ebru

  Introduction/Objective: Letrozole (LTZ)-loaded polymeric nanoparticles (PNPs) were formulated with Eudragit® RS100 to investigate their potential as a preliminary drug delivery system for hepatocellular carcinoma (HCC). Methods: Nanoparticles were prepared using the spray-drying technique with a Büchi B-90 Nano Spray Dryer and characterized in terms of morphology, particle size, polydispersity index (PDI), zeta potential, drug loading efficiency, thermal and structural characteristics, in vitro release behavior, and preliminary cytotoxicity. Results: Scanning electron microscopy (SEM) analysis demonstrated the formation of predominantly spherical particles with relatively smooth surfaces. The prepared nanoparticles exhibited initial particle sizes ranging between 253 nm and 425 nm, with PDI values of 0.3–0.4 and positive zeta potential values between 36 and 48 mV. Encapsulation efficiency (EE%) and drug loading (DL%) values were determined as 47.9%–56.9% and 9.1%–18.6%, respectively. Thermal and structural analyses indicated the molecular dispersion of LTZ within the polymeric matrix. In vitro release studies conducted at pH 7.4 demonstrated an initial burst release, followed by a sustained drug release profile over 24 h, with cumulative drug release reaching almost 80%. The preliminary cytotoxicity of the formulations was evaluated using the methylthiazolyl-diphenyl-tetrazolium bromide (MTT) assay on human hepatocellular carcinoma (HepG2) and healthy human dermal fibroblast (BJ) cell lines. Free LTZ demonstrated an IC50 value of 142.76 μg/mL against HepG2 cells, whereas the optimized nanoparticle formulation exhibited an IC50 value higher than 121.85 μg/mL. Discussion: The obtained results confirmed the successful development of LTZ-loaded polymeric nanoparticles with suitable physicochemical properties, efficient drug encapsulation, and sustained release behavior. The positive surface charge and nanoscale size may support formulation stability. Furthermore, the nanoparticles preserved the cytotoxic activity of LTZ, indicating their potential as an effective drug delivery system. Conclusion: Overall, the findings suggest that the developed nanoparticles constitute a promising drug delivery system for further investigation in HCC-related therapy. However, additional mechanistic studies and in vivo evaluations are required to comprehensively assess their true therapeutic potential. 2026, The Author(s).

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• ArticleYayıncıda açık erişim2026/r/ebyu/11080
  Evaluation of the Efficacy of Acarbose on Ovarian Microbiota Profile, Ovary–Gut Axis, and SAP (1–10) Gene Expression in Rats Administered With Candida albicans Exosomes

  Dabanlioglu, Bulent; Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Guler, Mustafa Can; Tanyeli, Ayhan; Ari, Betul; Kalayci, Sıla Ektas; Fakirullahoglu, Mesud; Kiliclioglu, Metin

  Candida albicans is a commensal fungus of the vaginal and reproductive tract microbiota, but its overgrowth contributes to mucosal infections and reproductive dysfunctions. The fungus secretes exosomes carrying virulence factors, including secreted aspartyl proteinase (SAP) genes, which are critical for tissue invasion and immune modulation. Acarbose, an α-glucosidase inhibitor, has been shown to suppress C. albicans biofilm formation and hyphal transition. This study is aimed at evaluating the effects of acarbose on the ovarian microbiota, gut–ovary axis, and SAP gene expression profile in a rat model following exposure to C. albicans exosomes. Rats were divided into two groups: the control group received intraperitoneal C. albicans exosomes (8 log10 CFU/mL), whereas the acarbose group received the same exosomes followed by oral acarbose (25 mg/kg/day). Exosomes were characterized by NTA and SEM. Ovarian tissue gene expression (SAP1–10) was analyzed by qRT-PCR. Inflammatory cytokines and tight junction proteins were assessed via ELISA, and microbiota composition was determined using 16S rRNA sequencing. Acarbose significantly reduced IL-8 and TNF-α levels while increasing IL-10, ZO-1, claudin-5, and occludin expression compared with Candida-infected controls (p < 0.05). Gut microbiota diversity and classification success were higher in the acarbose group, indicating microbial balance restoration. Acarbose mitigated C. albicans exosome-induced inflammation and barrier dysfunction while enhancing microbial diversity, suggesting its potential role in modulating the ovarian–gut axis and reducing fungal virulence through SAP gene suppression.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10922
  Alternative therapy against CTX-M broad spectrum β-lactamase resistance gene in Klebsiella pneumoniae infection: bee venom and bee venom-derived nanovesicle fraction

  Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Taghizadehghalehjoughi, Ali; Dabanlıoglu, Bulent; Guler, Mustafa Can; Aydın, Elif; Yıldırım, Serkan

  Antibiotic resistance is one of the most important problems threatening global public health by complicating the treatment of infections worldwide. The increase in resistant microorganisms creates a serious economic and social burden on healthcare systems and increasingly limits treatment options. Conscious use of antibiotics, infection control measures and the development of alternative treatment strategies are vital to ensure sustainability in health. Klebsiella pneumoniae is the most common gram-negative bacterium among urinary tract infections. Treatment of infections has become difficult due to the resistance to beta-lactam antibiotics. Bee venom (BV) and nanovesicle fractions isolated from BV are bioactive compounds with antimicrobial and antibiofilm activity. The aim of this study was to determine the antimicrobial and antibiofilm effects of BVand bee venom-derived nanovesicle fractions against the nosocomial infection agent K. pneumoniae, and to evaluate CTX-M PCR band detection under the tested conditions. Minimum inhibitory concentration (MIC), antibiofilm activity, fractional inhibition concentrations (FIC), CTX-M PCR band detection, and viability rates in L929 cells were evaluated for both BVand the bee venom-derived nanovesicle fraction against K. pneumoniae. MIC value of nanovesicle fractions isolated from BVwas determined as 1.95 mg/L. In combination with piperacillin and tazobactam, a synergistic effect was detected with a value of 0.5. Antibiofilm activity was measured with the highest absorbance value of 0.163 and 0.094 for BV nanovesicle fractions. A detectable CTX-M PCR band was observed in the BVgroup at 0.5× MIC, whereas no detectable band was observed at both concentrations by day 4. In the bee venom-derived nanovesicle fraction group, no detectable CTX-M PCR band was observed at 2× MIC and 0.5× MIC under the tested conditions. In contrast, detectable CTX-M PCR bands were observed in the piperacillin-tazobactam group. It was reported that the combination groups decreased the viability rate in L929 cell lines. The bee venom-derived nanovesicle fraction showed antimicrobial, antibiofilm, and PCR-based detection findings under the tested conditions, supporting the need for further investigation in broader in vitro and in vivo models.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10759
  Redox-mediated activation of PI3K/PTEN pathways by A. baumannii OMV–V. myrtillus conjugate in pancreatic cancer cells

  Celebi, Demet; Baser, Sumeyye; Mahmoudnezhad, Aydin; Ari, Betul; Celebi, Ozgur; Genc, Sidika; Nigde, Esmanur; Karabulut, Kubra; Taghizadehghalehjoughi, Ali

  Pancreatic cancer (PC) is one of the most aggressive malignancies of the digestive system, characterized by late diagnosis, resistance to conventional therapies, and poor survival outcomes. Therefore, the development of novel, effective, and targeted therapeutic strategies is urgently needed. This study aimed to evaluate the anticancer potential of Acinetobacter baumannii-derived outer membrane vesicles (OMVs) conjugated with Vaccinium myrtillus extract, a low-toxicity natural compound, against pancreatic cancer cells. For this purpose, V. myrtillus was conjugated with A. baumannii-derived OMVs, and the antimicrobial activity of the conjugate was assessed using disk diffusion, minimum inhibitory concentration, time-kill kinetics, and biofilm inhibition assays. The anticancer effects were investigated by treating PANC-1 pancreatic cancer cells and healthy fibroblast cells with OMVs (50 µg/mL) and increasing concentrations of V. myrtillus (5–250 µg/mL). After 24 h, cell viability and cytotoxicity (MTT, LDH), oxidative stress parameters (TAS, TOS, SOD, GR), PI3K/AKT/PTEN signaling pathway components, apoptotic markers (Annexin V/PI, BAX, Bcl-2, Caspase-8), and inflammatory cytokines (IL-1β, IL-10) were analyzed. The OMV–V. myrtillus conjugate (50 µg/mL OMV +250 µg/mL V. myrtillus) significantly reduced cell viability by approximately 60% through disruption of intracellular redox balance. Elevated oxidative stress triggered apoptotic signaling, approximately increased 50% LDH release, and enhanced inflammatory responses. Especially 50 µg/mL OMV +250 µg/mL V. myrtillus treatment group compared to the control group, which approximately increased to 1-fold IL-1β rate. Furthermore, the 50 µg/mL OMV +250 µg/mL V. myrtillus treatment group showed approximately a 0.75-fold increase in PTEN and BAX gene expression, accompanied by a correlated decrease in AKT and BCL-2 gene expression, compared to the control group. These results suggest that OMV-mediated delivery of V. myrtillus represents a promising synergistic therapeutic approach for treatment-resistant pancreatic cancer.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10665
  Rhodanine–Sulfonate hybrids targeting aldose reductase: Synthesis, in vitro inhibition, molecular docking, and cytotoxicity studies

  Kalay, Erbay; Demir, Yeliz; Türkeş, Cüneyt; Aslan, Osman Nuri; Pezik, Esra; Şahin, Engin

  Aldose reductase (ALR2), a key enzyme in the polyol pathway, plays a significant role in the onset and progression of diabetic complications, rendering it a critical pharmacological target. In this study, a novel series of twenty-four sulfonate ester-functionalized rhodanine derivatives (compounds 1–24) were rationally designed, synthesized via Knoevenagel condensation, and comprehensively evaluated for their inhibitory activity against ALR2. Spectroscopic and spectrometric methods confirmed the structural integrity of the synthesized compounds. In vitro enzyme inhibition assays revealed that all compounds acted as competitive inhibitors, with several analogues, particularly compounds 6 and 8, exhibiting stronger ALR2 inhibition (Ki = 0.43 µM and 0.48 µM, respectively) than the reference drug epalrestat (Ki = 0.98 µM). Structure–activity relationship (SAR) analysis highlighted the critical influence of para-substituted electron-donating (e.g., methyl) and electron-withdrawing (e.g., nitro, halogen) groups on binding potency. Molecular docking of the most potent inhibitor (compound 6) demonstrated a stable binding pose supported by key interactions, including hydrogen bonding with His110 and π–π stacking with Phe122. In silico ADME profiling confirmed favorable drug-likeness properties for all derivatives. Cytotoxicity studies on L929, A549, and RG-2 cell lines revealed that most compounds were less toxic than the reference drug at lower concentrations, with compound 8 showing a promising cytotoxic profile. These findings position rhodanine–sulfonate hybrids as promising scaffolds for the development of next-generation ALR2 inhibitors for the treatment of diabetic complications.

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• ArticleYalnız künye2026/r/ebyu/10649
  Evaluation of the protective effects of different antioxidants against the toxicity of herpes simplex virus 1 glycoprotein D

  Işik, Gözde; Çakir, Deniz Arca; Yirün, Anil; Erdemli-Köse, Selinay Başak; Özçelik, İbrahim; Erkekoǧlu, Pinar

  Herpes simplex virus type 1 (HSV-1) infects an estimated 3.8 billion people under age 50 worldwide and establishes lifelong neuronal latency, leading to recurrent disease manifestations such as neonatal and genital herpes; yet no vaccine or curative therapy exists. This study evaluated the oxidative-stress-modulating effects of HSV-1 glycoprotein D (gD) alone or in combination with two antioxidant agents - ascorbic acid and sodium selenite - in a human neuroblastoma cell line. Key oxidative-stress markers - including total glutathione (GSH), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), 8-isoprostane and protein carbonyl content - were quantified following exposure to "gD,""gD plus ascorbic acid", or "gD plus sodium selenite". Additionally, molecular docking analyses compared the binding affinities of ascorbic acid and sodium selenite for gD. Results showed that co-administration of ascorbic acid or sodium selenite with gD significantly elevated reactive oxygen species (ROS) levels compared to gD, while GSH and protein carbonyl concentrations remained unchanged. Intermediate lipid-peroxidation products did not differ significantly across treatment groups. Docking studies suggested that ascorbic acid exhibits a stronger potential for biologically relevant interaction with gD than sodium selenite, indicating a more pronounced antioxidant effect. These findings underscore the complexity of gD-induced oxidative pathways and highlight the need for further in vitro and in vivo investigations to delineate the toxicological impact of HSV-1 gD, as well as to extend analysis to other viral proteins involved in oxidative stress.

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• ArticleYalnız künye2026/r/ebyu/10207
  Development of nimesulide-loaded pH-triggered ocular in situ gels: in vitro characterization, MTT assay, and Drazie test

  Karakuyu, Nasif Fatih; Polat, Heybet Kerem; Unal, Sedat; Haydar, Muhammet Kerim; Mokhtare, Behzad; Aykurt, Furkan; Aksit, Aleyna

  Objective: The present study created nimesulide-loaded in situ gels and assessed their potential application in ocular inflammation. Methods: Because in situ gels have a low viscosity, sodium alginate, and hydroxypropyl methylcellulose combined to create a nimesulide CD complex that is easy to apply. However, due to the gelation creation with pH, washing and removing it from the ocular surface becomes challenging. Production was carried out using different ratios of sodium alginate, hydroxypropyl methylcellulose, and hyaluronic acid. Results: Characterization studies led to the determination of the optimized formulation. The optimized formulation viscosity pH 5.5 = 547.3 ± 76cP, viscosity pH 7.4 = 8798.3 ± 254 cP, and pH = 5.4 ± 0.01 were obtained. In in vitro release experiments, approximately 53% of nimesulide was released by burst action within 2 h, followed by a controlled release over 12 h. Mathematical modeling of the formulations’ release kinetics revealed that they were consistent with the Korsemeyer-Peppas and Weibull models. It was determined that nimesulide-loaded in situ gels showed over 80% viability in the L929 cell line. Rats underwent no adverse conditions in Draize’s in vivo experiment. Conclusion: For this reason, the TB5 formulation may be a good choice when treating ocular inflammation. These findings may be supported by future efficacy studies using this formulation.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10063
  Preparation and comparative evaluation of ondansetron hydrochloride loaded liposomes and lipid polymer hybrid nanoparticles

  Ozdal, Zeliha Duygu; Recber, Tuba; Demirel, Murside Ayse; Gultekin, Yakup; Nemutlu, Emirhan; Vural, Imran; Takka, Sevgi

  Chemotherapy-induced nausea and vomiting (CINV) typically occurs in two distinct phases: an acute phase, which arises within the first 24 h following chemotherapy, and a delayed phase, which develops between 24 and 120 h afterward. While acute CINV is now effectively controlled using 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, managing delayed CINV remains a significant clinical challenge. This study was aimed to develop Ondansetron hydrochloride (OND), loaded nanocarriers featuring high encapsulation efficiency (EE), to enable sustained drug release over several days. OND loaded sustained release liposome and lipid polymer hybrid polymeric nanoparticle (LPHNP) were prepared. The prepared formulations were characterized in terms of particle size and distribution, zeta potential, encapsulation efficiency and drug release in an in vitro study. The effects of the type of phospholipids, phospholipid/cholesterol molar ratio, and pH of hydration medium on liposome formulations were examined. In LPHNP formulations, the effect of external water phase volume, phospholipid type, preparation method, and pH of the aqueous phase was evaluated. In vitro cytotoxicity of the formulations was determined using L929 fibroblast cells. Optimum LPHNP formulation and the commercial product (Zofer®) were administered subcutaneously in a single dose to Wistar albino rats. It was found higher Cmax and MRT in LPHNP formulations than Zofer®. In this study, the effectiveness and safety of Ondansetron hydrochloride loaded LPHNP formulations were determined.

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• ArticleYalnız künye2025/r/ebyu/12065
  Development of lacosamide-loaded in-situ gels through experimental design for evaluation of ocular irritation in vitro and in vivo

  Çoban, Özlem; Pınar, Sıla Gülbağ; Polat, Heybet Kerem; Gedik, Gülşah; Karakuyu, Nasıf Fatih; Pezik, Esra; Ünal, Sedat; Mokhtare, Behzad; Akşit, Aleyna

  Lacosamide (LCM) selectively increases the slow inactivation of voltage-gated sodium channels (VGSCs) and is a N-methyl D-aspartate acid (NMDA) receptor glycine site antagonist. Therefore, it can be used in dryness-related hyperexcitability of corneal cold receptor nerve terminals. Ocular in-situ gels remain in liquid form until they reach the target site, where they undergo a sol-gel transformation in response to specific stimuli. They can show mucoadhesive properties related to the polymer used and increase the residence time of the drug in the mucosa. In the presented study, ocular in-situ gel formulation of LCM, which has potential for use in ocular diseases and consists of hyaluronic acid and poloxamer 407 as polymers, was developed using cold method. The effect of formulation components on target product properties (pH, gelation temperature and viscosity) was evaluated by design of experiments (DoE) design. The optimized LCM-loaded in-situ gel had a pH value of 6.90 ± 0.01, showed pseudo-plastic flow with a viscosity of 562 ± 58 cP at 25 °C, gelled at 33 ± 0.47 °C, and released drugs via the Peppas-Sahlin mechanism. Ocular safety was confirmed via in vitro tests using two different cell lines (L929 and Arpe-19), along with in vivo Draize tests, histological examinations, and Hen's Egg Chario-Allontioc-Membrane (HET-CAM) analysis. In vitro studies confirmed the optimized LCM-loaded in-situ gel's suitability for ocular use, demonstrating long-acting effects through controlled release. In addition, ocular irritation and histological studies have supported that it will not show any toxic effect on the eye tissue.

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