Flavonoid türevlerinin pickering emülsiyonu yöntemiyle kaplanarak üretimi ve enzim inhibisyonu üzerine etkisinin değerlendirilmesi
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Tarih
2024
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Yayıncı
Necmettin Erbakan Üniversitesi, Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Meyve, sebze, tahıl ve içeceklerde bulunan flavanoidler; antioksidan, antienflamatuvar, antikarsinojenik, antiviral ve antibakteriyel özellikleriyle öne çıkmaktadır. Flavonoidlerin birçok hastalığa karşı koruyucu özellik gösterdiği, inflamasyon mekanizmasını düzenleyerek nörodejenerasyonu engellediği veya gerilettiği düşünülmektedir. Ayrıca, flavonoidlerin antioksidan özellikleri sayesinde oksidatif stresi azalttığı bilinmektedir. Oksidatif stres arttıkça Alzheimer hastalığının evreleri de şiddetlenmektedir. Stabilite ve düşük biyoyararlanım sorunları olan flavonoidlerin bu dezavantajları, enkapsülasyon işlemi sayesinde avantaja çevrilebilmektedir. Modifiye salım sistemleriyle ise flavonoidlerin doğru yerde salımı sağlanarak biyoyararlanımlarının artırılması hedeflenmektedir. Tez çalışmasında, Pickering emülsiyonu ve iyonik jelasyon yöntemi ile kaplanacak olan rutin, naringin ve hesperidin flavonoidleri, önce zeytinyağı ve ayçiçek yağı ile emülsifikasyon işleminden geçirilmiş ve iyonik jelasyon yöntemi ile partiküller elde edilmiştir. Bu süreçte partiküllerin karakteristik analizleri yapılıp boyutları belirlenerek, etken madde miktarı ve enkapsülasyon verimliliği ölçülmüştür. Düşük çözünürlük ve biyoyararlanım ile stabilite problemleri olan narenciye flavonoidleri metabolizmanın düzenli çalışması için hayati önem taşır. Enkapsüle edilen flavonoidlerin, kolinesteraz enzimlerinin inhibisyonu yolu ile Alzheimer hastalığına etkisinin incelenmesi hedeflenmiştir. Çalışma bu yönüyle, Pickering emülsiyonu ve iyonik jelasyonunun pH duyarlı salımın uygulandığı yenilikçi bir çalışmadır. Çalışma özellikle bağırsak pH’ında yüksek stabiliteye sahip enkapsüle edilmiş ürünlerin geliştirilmesi bakımından önem arz etmektedir. Mide ve bağırsak ortamı canlandırılarak dissolüsyon analizi yapılmış ve enzim kinetiği belirlenmiştir. Optimizasyon çalışmaları sonucunda uygun yöntem, uygun su içinde yağ (S/Y) oranı ve kapsüllenecek etken madde miktarları bulunmuştur. Çalışmalar sonucunda her etken maddenin 7,5 mg, 15 mg ve 30 mg yüklenmesine karar verilmiştir. Mide ve bağırsak ortamını simüle eden iki farklı pH değerinde (pH 1,2 ve pH 7,4) dissolüsyon çalışması yapılmıştır. Çalışmada öngörüldüğü gibi partiküller bağırsak ortamında mide ortamına göre daha fazla salım yapmıştır. Enkapsülasyon etkinliği, salım profili ve antikolinesteraz enzimine etkileri ile birlikte değerlendirildiğinde, zeytinyağı ile birlikte kapsüllenen 30 mg naringin etken maddesinin tezde öne çıkarmak istenilen enzim inhibisyonu üzerinde diğer etken maddelere ve enkapsüle edilen partiküllere göre daha yüksek asetilkolinesteraz ve bütirilkolinesteraz enzim inhibisyonu gösterdiği görülmüştür. Flavonoidlerin bağırsak pH’ında biyoyararlanımını arttırmak ve yüksek stabiliteye sahip enkapsüle ürün elde etmek için yaptığımız bu çalışmada, partiküller pH 7,4’te tamamen parçalanmıştır ve etken maddeler açığa çıkmıştır. Mide ortamında (pH 1,2) salım yaklaşık %25'lerde gerçekleşirken, bağırsak ortamındaki (pH 7,4) 96 saat sonucunda %75 ila %82 arasında erken madde salımı gerçekleşmiştir. Elektroeğirme tekniği sayesinde, flavonoidlerin biyolojik kullanılabilirliği artırılarak, ilaç taşıma sistemleri, gıda ambalajları ve kozmetik ürünler gibi farklı alanlarda potansiyel uygulamalar geliştirilmesi amaçlanmıştır. Elde edilen fiberlerin morfolojik çalışmaları ile flavonoidlerin fiber matris içerisindeki dağılımı ve salım davranışları belirlenmiştir. Aynı zamanda, nanofiberlerin Staphylococcus aureus (S. aureus) bakterisine karşı antibakteriyel aktivitesi değerlendirilmiştir. Yapılan çalışmanın sonucunda bağırsak pH’ında (pH 7,4) yapılan dissolüsyon analizinde PLA-MIX fiberi içerisindeki etken maddeler %20-25 oranında, PCL- MIX fiberi içerisindeki etken maddeler %21-28 oranında salınmıştır. Antibakteriyel etki çalışmasının sonuçları nanofiberlerin %45 oranında PLA karışımında daha fazla bakteriyel inhibisyona neden olduğunu göstermiştir.
Flavonoids found in fruits, vegetables, grains and beverages stand out with their antioxidant, anti inflammatory, anticarcinogenic, antiviral and antibacterial properties. It is thought that flavonoids have protective properties against many diseases and prevent or delay neurodegeneration by regulating the inflammation mechanism. In addition, it is known that flavonoids reduce oxidative stress thanks to their antioxidant properties. As oxidative stress increases, the stages of Alzheimer's disease also intensify. These disadvantages of flavonoids, which have stability and low bioavailability problems, can be turned into advantages thanks to the encapsulation process. With modified release systems, it is aimed to increase the bioavailability of flavonoids by ensuring their release in the right place. In the thesis study, rutin, naringin and hesperidin flavonoids, which will be coated with Pickering emulsion and ionic gelation method, were first subjected to emulsification process with olive oil and sunflower oil and particles were obtained with ionic gelation method. In this process, characteristic analyses of particles were performed and their sizes were determined, and the amount of active ingredient and encapsulation efficiency were measured. Citrus flavonoids, which have low solubility, bioavailability and stability problems, are vital for the regular functioning of metabolism. The aim was to examine the effect of encapsulated flavonoids on Alzheimer's disease by inhibiting cholinesterase enzymes. In this respect, the study is an innovative study in which pH-sensitive release of Pickering emulsion and ionic gelation was applied. The study is especially important in terms of developing encapsulated products with high stability at intestinal pH. Dissolution analysis was performed by simulating the stomach and intestinal environment and enzyme kinetics were determined. As a result of the optimization studies, the appropriate method, appropriate oil-in-water (W/Y) ratio and the amount of active ingredient to be encapsulated were found. As a result of the studies, it was decided to load each active ingredient at 7.5 mg, 15 mg and 30 mg. Dissolution studies were performed at two different pH values (pH 1.2 and pH 7.4) simulating the stomach and intestinal environment. As predicted in the study, the particles released more in the intestinal environment than in the stomach environment. When evaluated together with the encapsulation efficiency, release profile and effects on the anticholinesterase enzyme, it was observed that 30 mg naringin active ingredient encapsulated with olive oil showed higher acetylcholinesterase and butyrylcholinesterase enzyme inhibition compared to other active ingredients and encapsulated particles on the enzyme inhibition desired to be highlighted in the thesis. In this study, which we conducted to increase the bioavailability of flavonoids in intestinal pH and to obtain an encapsulated product with high stability, the particles were completely disintegrated at pH 7.4 and the active ingredients were released. While the release in the stomach environment (pH 1.2) was approximately 25%, early substance release was between 75% and 82% after 96 hours in the intestinal environment (pH 7.4). By means of electrospinning technique, it is aimed to develop potential applications in different areas such as drug delivery systems, food packaging and cosmetic products by increasing the bioavailability of flavonoids. The distribution and release behaviors of flavonoids in the fiber matrix were determined by morphological studies of the obtained fibers. At the same time, the antibacterial activity of nanofibers against Staphylococcus aureus (S. aureus) bacteria was evaluated. As a result of the study, in the dissolution analysis performed at intestinal pH (pH 7.4), the active substances in PLA-MIX fiber were released at a rate of 20-25% and in PCL-MIX fiber at a rate of 21-28%. The results of the antibacterial effect study showed that nanofibers caused more bacterial inhibition in 45% PLA mixture.
Flavonoids found in fruits, vegetables, grains and beverages stand out with their antioxidant, anti inflammatory, anticarcinogenic, antiviral and antibacterial properties. It is thought that flavonoids have protective properties against many diseases and prevent or delay neurodegeneration by regulating the inflammation mechanism. In addition, it is known that flavonoids reduce oxidative stress thanks to their antioxidant properties. As oxidative stress increases, the stages of Alzheimer's disease also intensify. These disadvantages of flavonoids, which have stability and low bioavailability problems, can be turned into advantages thanks to the encapsulation process. With modified release systems, it is aimed to increase the bioavailability of flavonoids by ensuring their release in the right place. In the thesis study, rutin, naringin and hesperidin flavonoids, which will be coated with Pickering emulsion and ionic gelation method, were first subjected to emulsification process with olive oil and sunflower oil and particles were obtained with ionic gelation method. In this process, characteristic analyses of particles were performed and their sizes were determined, and the amount of active ingredient and encapsulation efficiency were measured. Citrus flavonoids, which have low solubility, bioavailability and stability problems, are vital for the regular functioning of metabolism. The aim was to examine the effect of encapsulated flavonoids on Alzheimer's disease by inhibiting cholinesterase enzymes. In this respect, the study is an innovative study in which pH-sensitive release of Pickering emulsion and ionic gelation was applied. The study is especially important in terms of developing encapsulated products with high stability at intestinal pH. Dissolution analysis was performed by simulating the stomach and intestinal environment and enzyme kinetics were determined. As a result of the optimization studies, the appropriate method, appropriate oil-in-water (W/Y) ratio and the amount of active ingredient to be encapsulated were found. As a result of the studies, it was decided to load each active ingredient at 7.5 mg, 15 mg and 30 mg. Dissolution studies were performed at two different pH values (pH 1.2 and pH 7.4) simulating the stomach and intestinal environment. As predicted in the study, the particles released more in the intestinal environment than in the stomach environment. When evaluated together with the encapsulation efficiency, release profile and effects on the anticholinesterase enzyme, it was observed that 30 mg naringin active ingredient encapsulated with olive oil showed higher acetylcholinesterase and butyrylcholinesterase enzyme inhibition compared to other active ingredients and encapsulated particles on the enzyme inhibition desired to be highlighted in the thesis. In this study, which we conducted to increase the bioavailability of flavonoids in intestinal pH and to obtain an encapsulated product with high stability, the particles were completely disintegrated at pH 7.4 and the active ingredients were released. While the release in the stomach environment (pH 1.2) was approximately 25%, early substance release was between 75% and 82% after 96 hours in the intestinal environment (pH 7.4). By means of electrospinning technique, it is aimed to develop potential applications in different areas such as drug delivery systems, food packaging and cosmetic products by increasing the bioavailability of flavonoids. The distribution and release behaviors of flavonoids in the fiber matrix were determined by morphological studies of the obtained fibers. At the same time, the antibacterial activity of nanofibers against Staphylococcus aureus (S. aureus) bacteria was evaluated. As a result of the study, in the dissolution analysis performed at intestinal pH (pH 7.4), the active substances in PLA-MIX fiber were released at a rate of 20-25% and in PCL-MIX fiber at a rate of 21-28%. The results of the antibacterial effect study showed that nanofibers caused more bacterial inhibition in 45% PLA mixture.
Açıklama
Doktora Tezi
Anahtar Kelimeler
Alzheimer Hastalığı, Antikolinesteraz Enzim İnhibisyonu, Elektroeğirme, Hesperidin, Naringin, Pickering Emülsiyonu, Rutin Hidrat, Alzheimer's Disease, Anticholinesterase Enzyme İnhibition, Pickering Emulsion, Rutin Hydrate
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Algan, D. T. (2024). Flavonoid türevlerinin pickering emülsiyonu yöntemiyle kaplanarak üretimi ve enzim inhibisyonu üzerine etkisinin değerlendirilmesi. (Yayımlanmamış doktora tezi). Necmettin Erbakan Üniversitesi, Fen Bilimleri Enstitüsü Kimya Anabilim Dalı, Konya.
