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    Design and characterization of antibiotic-free lyotropic liquid crystalline coatings based on binary docosahexaenoic acid monoglyceride/glycerol monooleate systems for combating orthopedic implant-associated infections
    (Academic Press Inc Elsevier Science, 2026) Akay, Seref; Ciofu, Oana; Gow, Jonathan Michael; Posselt, Dorthe; Marmiroli, Benedetta; Sartori, Barbara; Yaghmur, Anan
    There is a growing interest in innovative strategies for effectively preventing implant-associated bacterial infections. Here, we report on a simple-by-design approach for production of antibacterial coatings from docosahexaenoic acid monoacylglycerol (MAG-DHA) and glycerol monooleate (GMO). In addition to its amphiphilic nature, MAG-DHA is a safe precursor of docosahexaenoic acid (DHA) and has different beneficial health effects, including antibacterial activities. Using binary combinations of MAG-DHA and GMO, we describe the structural features and the antibacterial activities of antibiotic-free non-lamellar liquid crystalline (LLC) coatings. Small-angle X-ray scattering (SAXS) and in situ grazing incidence small-angle X-ray scattering (GISAXS) were employed to gain insight into the structural features of the fully hydrated coatings and the hydration-induced dynamic self-assembly of MAG-DHA and GMO on model implants. In a lipid composition-dependent manner, SAXS results revealed hydration-induced formation of different inverse LLC self-assemblies, including hexagonal (H2) and bicontinuous cubic (Q2) phases. Further, GISAXS analysis showed that lipid composition and employed relative humidity level play important roles in controlling the out-of-equilibrium self-assembly properties. Moreover, the coatings containing MAG-DHA displayed unique inherent antibacterial activities against Staphylococcus aureus and Staphylococcus epidermidis strains. This study describes the first antibiotic-free coatings with nanostructural architectures and inherent antibacterial activities for orthopedic implants.
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    Design and fabrication of low-cost microsystems for production of chitosan particles
    (Gazi Univ, Fac Engineering Architecture, 2024) Akay, Seref; Ozdilek, Hasret
    Recent research has focused on the methods for administration of medications in a controlled manner while minimizing side effects. Cross -linked hydrogels have wide application area as nanocarriers. There are many approaches for developing suitable methods to produce ideal particles. Advances in microtechnology have been considered as a solution to produce controlled drug delivery systems, however, it is limited due to the necessity for specialized laboratories. In this study, a simple method to produce antibiotic -loaded chitosan particles is proposed. Production was carried out with two different designs, a syringe -based flow focusing system (outer diameter of 1 mm, inner diameter of 120 mu m) and microchannel with 250 mu m width and 100 mu m height fabricated with the computer numerical control (CNC). Sodium Triphosphate (TPP) was used as cross -linking agent for the production of particles and the effects of the concentration and flow rates on the particle formation was investigated. It has been observed that particles can be produced in a syringe -based system, but the resulting particles are not homogeneous. In the studies carried out with CNC microchannel, it was determined by SEM analysis that the obtained particles ranged in size from 39 to 771 nm, and it was seen that the CNC microchannel was more effective at low and equal flow rates (25 mu l/min). It has been found that increasing the flow rate and concentration of chitosan increases the particle size. It was determined that Ampicillin loaded particles synthesized with the CNC microchannel exhibited high inhibition against Gram positive and Gram negative bacteria. These results show that the proposed approaches for the design of microsystems can be used in the formation of drug carriers without the need for specialized laboratories and expertise.
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    Determination of the Cytotoxicity and Antibiofilm Potential Effect of Equisetum arvense Silver Nanoparticles
    (Springer, 2024) Akar, Zeynep; Akay, Seref; Ejder, Nebahat; Duzgun, Azer Ozad
    This study aimed to synthesize and characterize silver nanoparticles (AgNPs) by green synthesis from Equisetum arvense (Ea) extracts and to investigate their cytotoxicity, antibiofilm activity, and alpha-glucosidase enzyme inhibition. Diverse characterization techniques were applied to verify the production of nanoparticles. SEM examination confirmed that the size of nanoparticles is in the range of 40-60 nm. Also, interactions between silver and natural compounds of plant extract were confirmed through FT-IR and EDX analyses. It was determined that Equisetum arvense silver nanoparticles had antibiofilm activity against three different clinical strains with high biofilm-forming ability. AgNPs reduced the biofilm-forming capacity of clinical A. baumannii isolate with strong biofilm-forming capacity by approximately twofold, while the capacity of clinical K.pneumonaie and E.coli isolates decreased by 1.5 and 1.2 fold, respectively. The alpha-glucosidase enzyme inhibition potential of the AgNPs, which is determined as 93.50%, was higher than the plant extract with, and the alpha- 30.37%. MTT was performed to assess whether incubation of nanoparticles with A549 and ARPE-19 cell lines affected their viability, and a dramatic reduction in cell growth inhibition of both A549 and ARPE-19 cells was observed. It has been shown that A549 cells treated with 200 and 150 mu g/mL nanoparticles had less cell proliferation compared to control cells at 24-h and 48-h incubation time. According to these results, Ea-derived AgNPs appear to have potential anticancer activity against A549 cancer cells. Investigating the effects of green synthesis nanoparticles on microbial biofilm and various tumors may be important for developing new therapies. The outcomes of this study have showed that Ea-AgNPsmay have a high potential both in the treatment of pathogenic strains that form biofilms, as well as in anticancer therapy use.
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    Investigation of Antibiofilm and Antibacterial Properties of Green Synthesized Silver Nanoparticles from Aqueous Extract of Rumex sp.
    (Springer, 2024) Akay, Seref; Yuksel, Gamze; Duzgun, Azer Ozad
    The decrease in the effectiveness of conventional drugs as a result of the growth of resistance to antibiotics has increased the need for innovative tools to control the infections. At this point, metallic nanoparticles, in particular silver nanoparticles, have appeared as a promising method. In the current study, the extract of Rumex sp. (Labada, dock) leaves was used as a reducing agent for the formation of silver nanoparticles. Unlike similar studies, in this study the synthesis conditions were optimized by changing the extract ratio and silver nitrate concentration. Morphological investigations of synthesized silver nanoparticles showed that spherical homogeneous particles at size under 100 nm had been produced. SEM/EDS and FTIR analyses showed that plant components are involved in the synthesis of nanoparticles. It was also determined that higher extract ratio reduced nanoparticle size. The antimicrobial effects of the synthesized nanoparticles against Gram-positive and Gram-negative bacteria were tested, and it was determined that all nanoparticles exhibited activity against both groups. Rumex sp. silver nanoparticles (NPs) were revealed to exhibit antibiofilm activity against three different isolates with moderate and strong biofilm-forming ability. The NPs reduced the biofilm-forming capacity of Acinetobacter baumannii and Klebsiella pneumonaie by 2.66-fold and 3.25-fold, whereas they decreased the Escherichia coli biofilm-forming capacity by 1.25-fold. The investigation of microbial biofilm could play an important role in developing new strategies for treatment options. Our results suggest that Rumex sp. silver NPs may have a high potential for use in the treatment of pathogenic strains.
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    Kitosan parçacıklarının üretimi için düşük maliyetli mikrosistemlerin tasarımı ve fabrikasyonu
    (2024) Özdilek, Hasret; Akay, Seref
    Son zamanlarda araştırmalar, ilaçların yan etkilerini en aza indirirken etkili ve kontrollü bir şekilde uygulanmasına imkan veren yöntemlere odaklanmıştır. Hidrofilik polimerik yapıdaki hidrojeller, nanotaşıyıcı olarak yaygın bir kullanım alanına sahiptir. Çapraz bağlanma ile oluşturulan ağ yapısı ilaçların tutulmasına ve taşınmasına elverişlidir. Boyut ve kararlılık gibi istenen özelliklere sahip parçacıkların üretiminde uygun yöntemlerin geliştirilmesi için birçok yaklaşım vardır. Mikroakışkan sistemlerindeki ilerlemeler sayesinde mikrosistemler, salım profilleri kontrol edilebilen karmaşık ilaç taşıyıcılarını üretmek için de çözüm olarak görülmüştür. Ancak, mikrofabrikasyon tekniklerinin, yüksek maliyeti ve özel laboratuvarlar gerektirmesi nedeniyle kullanımı sınırlı kalmaktadır. Bu çalışmada, antibiyotik yüklü kitosan parçacıklarının üretimi için basit ve ucuz bir yöntem önerilmiştir. Şırınga tabanlı akış odaklama sistemi (dış kanal capı 1 mm iç kanal çapı 120 µm) ve bilgisayarlı sayısal kontrol (Computer numerical control, CNC) yardımıyla tasarlanan, 2 giriş, 1 çıkış portuna sahip ve 250 µm genişliğinde ve 100 µm derinliğinde serpantin tipi mikrokanal olmak üzer iki farklı tasarımın üretimi gerçekleştirilmiştir. Kitosan parçacıkların üretimi için çapraz bağlayıcı ajan olarak Sodyum Trifosfat (TPP) kullanılmış ve bileşenlerin konsantrasyonu ve akış hızlarının parçacık oluşumuna etkileri incelenmiştir. Kitosan parçacıkların, şırınga tabanlı akış odaklama sisteminde üretilebildiği, ancak boyutlarını kontrol etmenin mümkün olmadığı ve elde edilen parçacıkların homojen olmadığı görülmüştür. CNC mikrokanal ile yapılan çalışmalarda üretilen parçacıkların 39 ila 771 nm arasında değişen boyutlarda olduğu SEM analizleri ile tespit edilmiş ve CNC mikrokanalın, düşük ve eşit akış hızlarında (25 µl/dk) daha başarılı olduğu görülmüştür. Kitosan akış hızının arttırılmasının, parçacık boyutunu büyük ölçüde arttırdığı, benzer şekilde kitosan konsanstrasyonun daha yüksek olduğu koşullarda da parçacık boyutunun arttığı tespit edilmiştir. CNC mikrokanal ile optimum koşullarda üretilen, Ampisilin yüklü parçacıkların Gram pozitif ve Gram negatif bakteriler üzerinde inhibisyon gösterdiği belirlenmiştir. Bu sonuçlar, mikrosistemlerin tasarımı için önerilen yaklaşımların özel laboratuvar ve uzmanlık gerektirmeksizin, polimerik ilaç taşıyıcılarının üretiminde kullanılabileceğini göstermektedir.