pH duyarlı dendrimer bağlanmış polimerik malzemelerin hazırlanması ve biyomedikal alanda kullanımı
Yükleniyor...
Dosyalar
Tarih
2019
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Bu tez çalıĢmasında kontrollü ilaç salım çalıĢmalarında kullanılmak üzere mikrokristalin selüloz (MKS) ve polivinil alkol (PVA) ana zincirine bağlı poliamidoamin (PAMAM) ve poliester (PEs) dendrimerler sentezlendi ve ülseratif kolit tedavisinde etken madde olarak kullanılan 5-aminosalisilik asit (5-ASA)'in değiĢik pH'larda salımı araĢtırıldı. 5–ASA etken maddesine sahip ilaçlar günde 6 defa ve toplamda günlük dozu 3–4 gram olmak üzere aktif ülseratif kolit tedavisinde ömür boyu alınması gereken ilaçlar arasındadır. Bu çalıĢmada 5–ASA'nın intestinal sisteminde uzun süreli kontrollü salımı sağlanarak günlük doz miktarının alım periyodunu uzatarak hasta konforunun sağlanması amaçlanmıĢtır. Bu amaçla, –NH2 fonksiyonel PAMAM ve –OH fonksiyonel poliester dendrimerler yakınsak ve ıraksak yöntemlerle MKS ve PVA ana omurgası üzerinde farklı jenerasyonlarda sentezlendi. 5–ASA'nın dendrimerlerin her bir jenerasyonunun kavitasyonlarında tutuklanan ve sindirim sisteminin mide, ince bağırsak ve kalın bağırsağın fizyolojik pH'larında (3,5; 7,4 ve 8,5) in-vitro koĢullarda salımı araĢtırıldı. Hem PAMAM hem de ester dendrimerlerden 5–ASA'nın salımı pH 3,5'da %50'nin altında iken pH'nın bazik bölgeye kaymasıyla arttığı görüldü. Dendrimerlerin jenereasyon sayısı arttıkça salınan 5–ASA miktarının da arttığı bulundu. Bunun nedeni, dendrimer jenerasyon sayısının artması bağlı olarak kavitasyonlarda tutuklanan 5–ASA miktarındaki artıĢtan kaynaklanmaktadır. pH'nın artmasıyla salımın artması ise 5–ASA'nın asit grubunun deprotonasyonu dolayısıyla misafir-ev sahibi arasındaki hidrojen bağlarının zayıflamasından kaynaklanmaktadır. ÇalıĢma kapsamında sentezlenen bileĢiklerin karakterizasyonları FT–IR, 1H NMR, TGA–DSC, SEM, XRD teknikleri ile 5–ASA salım çalıĢmaları ise UV-vis ile gerçekleĢtirildi.
In this thesis, for use in controlled drug release studies, polyamidoamine (PAMAM) and polyester (PEs) dendrimers which are bound to microcrystalline cellulose (MKS) and polyvinyl alcohol (PVA) main chain have been synthesized and the release of 5- aminosalicylic acid (5–ASA) used as active ingredient in the treatment of ulcerative colitis has been investigated at different pH. Medicines with the active ingredient 5–ASA are among the drugs in the treatment of active ulcerative colitis that need to be taken 6 times a day and total 3-4 grams daily dose for lifetime. In the present study was to provide long-term controlled release of 5–ASA in the intestinal tract and to decrease the daily dose and to provide patient comfort by prolonging the intake period. For this purpose, –NH2 functional PAMAM and –OH functional polyester dendrimers were synthesized by convergent and divergent methods on MKS and PVA main backbone in different generations. The release of 5–ASA in the cavitations of each generation of dendrimers was investigated conditions of in-vitro which the digestive system was in accordance with the physiological pH (3.5; 7.4 and 8.5) of the stomach, small intestine, and large intestine. While 5–ASA release from both PAMAM and ester dendrimers was below 50% at pH 3.5, it was seen that 5–ASA release was increased by shifting the pH to the basic region. As the number of generation of dendrimers increased, the amount of 5– ASA released was also found to be increased. This is due to the increase in the amount of 5– ASA in cavitations due to the increased dendrimer generation number.The increase of the release with the increase of the pH is stem from the weakening of the hydrogen bonds between guest and host due to the deprotonation of the 5–ASA acid group. Characterization of the synthesized compounds within this study was carried out with FT-IR, 1H NMR, TGA–DSC, SEM, XRD techniques and 5–ASA release studies were performed with UV-vis.
In this thesis, for use in controlled drug release studies, polyamidoamine (PAMAM) and polyester (PEs) dendrimers which are bound to microcrystalline cellulose (MKS) and polyvinyl alcohol (PVA) main chain have been synthesized and the release of 5- aminosalicylic acid (5–ASA) used as active ingredient in the treatment of ulcerative colitis has been investigated at different pH. Medicines with the active ingredient 5–ASA are among the drugs in the treatment of active ulcerative colitis that need to be taken 6 times a day and total 3-4 grams daily dose for lifetime. In the present study was to provide long-term controlled release of 5–ASA in the intestinal tract and to decrease the daily dose and to provide patient comfort by prolonging the intake period. For this purpose, –NH2 functional PAMAM and –OH functional polyester dendrimers were synthesized by convergent and divergent methods on MKS and PVA main backbone in different generations. The release of 5–ASA in the cavitations of each generation of dendrimers was investigated conditions of in-vitro which the digestive system was in accordance with the physiological pH (3.5; 7.4 and 8.5) of the stomach, small intestine, and large intestine. While 5–ASA release from both PAMAM and ester dendrimers was below 50% at pH 3.5, it was seen that 5–ASA release was increased by shifting the pH to the basic region. As the number of generation of dendrimers increased, the amount of 5– ASA released was also found to be increased. This is due to the increase in the amount of 5– ASA in cavitations due to the increased dendrimer generation number.The increase of the release with the increase of the pH is stem from the weakening of the hydrogen bonds between guest and host due to the deprotonation of the 5–ASA acid group. Characterization of the synthesized compounds within this study was carried out with FT-IR, 1H NMR, TGA–DSC, SEM, XRD techniques and 5–ASA release studies were performed with UV-vis.
Açıklama
Anahtar Kelimeler
Kimya, Chemistry
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Sezer, S. (2019). pH duyarlı dendrimer bağlanmış polimerik malzemelerin hazırlanması ve biyomedikal alanda kullanımı. Yayınlanmış Doktora Tezi, İnönü Üniversitesi.
