Doğal kaynaklardan glutatyon elde edilmesi, saflaştırılması ve farmasötik formda değerlendirilmesi
Küçük Resim Yok
Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Glutatyon (GSH), hücrelerde sentezlenen düşük molekül ağırlıklı glutamik asit, sistein ve glisin amino asitlerinden oluşan bir tripeptittir. GSH, hücreleri oksidatif hasardan ve ksenobiyotik elektrofillerin toksisitesinden korumanın yanı sıra redoks homeostazını sürdürmede kritik roller oynar. GSH, çok sayıda temel biyolojik süreçte yer alan ve çeşitli dejeneratif hastalıklara müdahalelerde kullanılan güçlü antioksidan aktiviteye sahiptir. GSH'ın oral yolla verilmesi gastrointestinal (GI) sistemdeki fizikokimyasal bariyerler nedeniyle diğer protein ve peptit ilaçlarına benzer şekilde zorlu olmaya devam etmekte ve düşük oral biyoyararlanıma neden olmaktadır. Dağılımı iyileştirmek için hidrojeller, nanopartiküller içine kapsülleme, mikroemülsiyonlar ve lipozomlar gibi klinik terapötik etkilere sahip uygun formülasyonlar yeni nesil stratejiler kullanılmaktadır. Bu çalışmada, öncelikle, donmuş ve taze brokoli (Brassica oleracea), ıspanak (Spinacia oleracea), lahana (Brassica oleracea var. capitata f. alba) ve semizotu (Portulaca oleracea)'dan etkili GSH düzeyleri elde edilmesini sağlandı. GSH'ı niceliksel olarak ve niteliksel olarak belirlemek için UV ve floresan dedektörlü HPLC kullanarak analitik yöntemler geliştirildi ve sonuçlar karşılaştırıldı. HPLC-UV sonuçlarına göre en yüksek GSH seviyesi liyofilize ıspanak bitkisi ile elde edilirken taze semizotu bitkisinden pik elde edilemedi. HPLC-FLD sonuçlarına göre en yüksek GSH seviyesi liyofilize ıspanak bitkisinde elde edilirken taze ve liyofilize semizotu bitkisinden pik elde edilemedi. HPLC sonuçları karşılaştırıldığında, sonuçlarda her iki analitik yöntem için de benzer sonuçlara ulaşıldı. Daha sonra araştırma, terapötik çalışmalar için farmasötik bir ürün geliştirme nihai hedefiyle GSH' ın biyoyararlılığını artırmaya yönelik stratejilere odaklandı. Bu amaçla doğal kaynaklı glutatyon bazlı enjekte edilebilir hidrojel ve ticari glutatyon bazlı enjekte edilebilir hidrojel tasarlandı. Kimyasal yapı açısından benzer sonuçlar elde edilirken, doğal kaynaklı glutatyon bazlı enjekte edilebilir hidrojelin daha iyi homojen bir dağılıma sahip olduğu gözlendi. Sonuçlar, doğal kaynaklı glutatyon bazlı enjekte edilebilir hidrojel stratejisinin, oldukça gelişmiş antioksidan ve biyoaktif özelliklere sahip yeni nesil GSH bazlı hidrojel için yeni bir strateji olduğunu göstermektedir.
Glutathione (GSH) is a tripeptide consist of low molecular weight glutamic acid, cysteine and glycine amino acids synthesized in cells. GSH plays critical roles in protecting cells from oxidative damage and the toxicity of xenobiotic electrophiles and maintaining redox homeostasis. GSH is with potent antioxidant activity, which is involved in numerous basic biological processes and has been used for interventions in various degenerative diseases. Oral delivery of GSH remains challenging similarly to that of other protein and peptide drugs, due to physicochemical barriers in the gastrointestinal (GI) tract, which cause to low oral bioavailability. To improve delivery, new generation strategies are used such as hydrogels, encapsulation into nanoparticles, microemulsions and liposomes, appropriate formulations with clinical therapeutic effects. In the thesis, first of all, that lyophilized and fresh broccoli (Brassica oleracea), spinach (Spinacia oleracea), cabbage (Brassica oleracea var. capitata f. alba), and purslane (Portulaca oleracea) were used to obtain efficient levels of GSH. We enhanced analytical methods both by using HPLC with an ultraviolet detector and a fluorescence detector to determine GSH quantitatively and qualitatively, and then compared the results. In the results of HPLC-UV, the highest level of GSH was obtained with the lyophilized spinach plant. However, no peak was obtained in fresh purslane. In the results of HPLC-FLD, the highest level of GSH was obtained with the lyophilized spinach plant. Likewise, no peak was obtained in fresh and lyophilized purslane. When the HPLC results were compared, the results achieved similar results for both analytical methods. Then, the research was focused on strategies to enhance the bioavailability of GSH, with the ultimate goal of developing a pharmaceutical product for therapeutic studies. To this end, natural-source glutathione-based injectable hydrogel and commercial glutathione-based injectable hydrogel were designed. While similar results were obtained in terms of chemical structure, a natural-source glutathione-based injectable hydrogel had a better homogeneous distribution. The results indicate that a novel strategy for a new generation GSH based on injectable hydrogel from natural sources with highly improved antioxidant and bioactive properties.
Glutathione (GSH) is a tripeptide consist of low molecular weight glutamic acid, cysteine and glycine amino acids synthesized in cells. GSH plays critical roles in protecting cells from oxidative damage and the toxicity of xenobiotic electrophiles and maintaining redox homeostasis. GSH is with potent antioxidant activity, which is involved in numerous basic biological processes and has been used for interventions in various degenerative diseases. Oral delivery of GSH remains challenging similarly to that of other protein and peptide drugs, due to physicochemical barriers in the gastrointestinal (GI) tract, which cause to low oral bioavailability. To improve delivery, new generation strategies are used such as hydrogels, encapsulation into nanoparticles, microemulsions and liposomes, appropriate formulations with clinical therapeutic effects. In the thesis, first of all, that lyophilized and fresh broccoli (Brassica oleracea), spinach (Spinacia oleracea), cabbage (Brassica oleracea var. capitata f. alba), and purslane (Portulaca oleracea) were used to obtain efficient levels of GSH. We enhanced analytical methods both by using HPLC with an ultraviolet detector and a fluorescence detector to determine GSH quantitatively and qualitatively, and then compared the results. In the results of HPLC-UV, the highest level of GSH was obtained with the lyophilized spinach plant. However, no peak was obtained in fresh purslane. In the results of HPLC-FLD, the highest level of GSH was obtained with the lyophilized spinach plant. Likewise, no peak was obtained in fresh and lyophilized purslane. When the HPLC results were compared, the results achieved similar results for both analytical methods. Then, the research was focused on strategies to enhance the bioavailability of GSH, with the ultimate goal of developing a pharmaceutical product for therapeutic studies. To this end, natural-source glutathione-based injectable hydrogel and commercial glutathione-based injectable hydrogel were designed. While similar results were obtained in terms of chemical structure, a natural-source glutathione-based injectable hydrogel had a better homogeneous distribution. The results indicate that a novel strategy for a new generation GSH based on injectable hydrogel from natural sources with highly improved antioxidant and bioactive properties.
Açıklama
Anahtar Kelimeler
Biyomühendislik, Bioengineering, Eczacılık ve Farmakoloji
