Sıcaklığa duyarlı poli(N,N-dietilakrilamid)'in aljinata aşılanması ve 5-fluorourasil salımında kullanımı
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Dosyalar
Tarih
2016
Yazarlar
Dergi Başlığı
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Cilt Başlığı
Yayıncı
Kırıkkale Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Tez çalışmasında, sodyum aljinata (NaAlg), N,N-dietilakrilamid (DEAAm) monomeri aşılandı ve sıcaklığa duyarlı oral ilaç taşıyıcı sistemlerin oluşturulması gerçekleştirildi. Sulu fazda sodyum aljinat-aşı-poli(N,N-dietilakrilamid) kopolimerleri, potasyum persülfat başlatıcıyla ve hızlandırıcı olarak N,N,N',N'-tetrametiletilendiamin (TEMED) kullanılarak mikrodalga fırında sentezlendi. Aşı yüzdesi ve aşılama verimi üzerine tepkime süresi, tepkime sıcaklığı, başlatıcı, TEMED, DEAAm, NaAlg derişimlerinin ve UV ışını etkileri incelendi. Optimum koşullarda aşı yüzdesi ve aşılama verimi sırasıyla % 301,06 ve % 55,35 olarak bulundu. Sodyum aljinat-aşı-poli(N,N-dietilakrilamid) kopolimerlerin yapıları ATR-FTIR, Raman, 1H-NMR, 13C-NMR, DSC, TGA ve GPC analizleri ile aydınlatıldı. Termal analiz sonuçlarından sentezlenen kopolimerlerin NaAlg'ye göre termal dayanımının yüksek olduğu bulundu. Yapıları aydınlatılan kopolimerler 5-Fluorourasil'in (5-FU) oral mikroküre uygulamasında kullanıldı. Sodyum aljinat-aşı-poli(N,N-dietilakrilamid) mikroküreleri gluteraldehit ile HCI katalizörlüğünde çapraz bağlanarak hazırlandı. İlaç yüklü mikroküreler tutuklanma verimleri, partikül boyutları ile karakterize edildi. Boş mikrokürelerin farklı pH ve sıcaklıktaki şişme dereceleri incelendi. Mikrokürelerden ilaç salımına aşı yüzdesinin, polimer derişiminin, ilaç/polimer oranının, çapraz bağlayıcı derişiminin, çapraz bağlama süresinin, pH ve sıcaklığın etkileri araştırıldı. Aşı yüzdesi 20 olan mikrokürelerde sıcaklığın 25 ºC'den 37 ºC'ye artırılmasıyla yüzde 5-FU salım sonucu 95'den 75'e, aşı yüzdesi 110 olan mikrokürelerde 75'den 43'e azaldı. Mikrokürelerin 5-FU yüzde salımı ve şişme derecesi verilerinden sıcaklığa duyarlılık sağladıkları, kontrollü salım gerçekleştirdikleri tespit edildi. Mikrokürelerde ilacın kimyasal kararlılığı ATR-FTIR ölçümleri ile doğrulandı. DSC analizi sonucundan mikrokürelere ilaç yüklenmesiyle camsı geçiş sıcaklığının arttığı ve XRD analizi sonuçları ile ilacın kristalin yapısını koruduğu görüldü. Yüzey morfolojileri SEM ve AFM analizleri ile incelendi. Kinetik parametreler salım sonuçlarından yararlanılarak hesaplandı. Difüzyon katsayısı polimerik mikrokürelerden ilacın difüzyonu için hesaplandı ve salım sonuçları ile uyumlu değerler bulundu. Gluteraldehit derişimi, HCI derişimi, çapraz bağlama süresinin artmasıyla difüzyon katsayılarında azalma görüldü.
In this study, N,N-diethylacrylamide (DEAAm) were grafted onto sodium alginate (NaAlg) and investigated formation of temperature sensitive oral drug delivery systems. Sodium alginate-graft-N,N-diethylacrylamide copolymers were synthesized in aqueous solutions by using potassium peroxodifülfate as initiator and N,N,N',N'-tetrametiletilendiamin (TEMED) as accelator in the microwave oven. The effect of reaction time, reaction temperature, TEMED, DEAAm, NaAlg concentrations and effect of UV irradiation onto grafting percentage and grafting efficiency were examined. The grafting percentage and grafting efficiency in optimum conditions were found to be 301.06 % and 55.35 %, respectively. The structures of sodium alginate-graft-poly(N,N-diethylacrylamide) copolymers were characterized by ATR-FTIR, Raman, 1H-NMR, 13C-NMR, DSC, TGA and GPC analyses. Thermal stability of synthesized copolymers was found higher than that of NaAlg. Copolymers characterized were used in oral microspheres application of 5-Fluorouracil (5-FU). Sodium alginate-graft-poly(N,N-diethylacrylamide) microspheres were prepared by crosslinking with glutaraldehyde in hydrochloric acid medium. Drug loaded microspheres were characterized with entrapment efficiency and particles size. Swelling degrees of empty microspheres were carried out at different pH and temperature. Effect of grafting yield, polymer concentration, drug/polymer ratio, crosslinking agent concentration, crossslinking time, pH and temperature on release of drug from microspheres were examined. 5-FU release from microspheres with 20 grafting percentage decreased from 95 to 75 with increasing temperature from 25 ºC to 37 ºC while release from microspheres with 110 grafting percentage decreased from 75 to 43. Release behavior and swelling degree of microspheres showed that obtained microspheres are thermoresponsive and be able to control the drug release. Chemical stability of drug in the microspheres was confirmed by ATR-FTIR measurements. DSC result showed that glass transition temperature increases with drug loading and XRD results demonstrated drug exist in crystaline structure. The surface morphology was investigated with SEM and AFM analysis. Kinetic parameters were determined by using release results. The diffusion coefficients were calculated for the transport of drug trought the polymeric microspheres and the results were found in accordance with the release results. It was shown that diffusion coefficients decreased with increasing glutaraldehyde concentration, HCI concentration, crosslinking time to glutaraldehyde.
In this study, N,N-diethylacrylamide (DEAAm) were grafted onto sodium alginate (NaAlg) and investigated formation of temperature sensitive oral drug delivery systems. Sodium alginate-graft-N,N-diethylacrylamide copolymers were synthesized in aqueous solutions by using potassium peroxodifülfate as initiator and N,N,N',N'-tetrametiletilendiamin (TEMED) as accelator in the microwave oven. The effect of reaction time, reaction temperature, TEMED, DEAAm, NaAlg concentrations and effect of UV irradiation onto grafting percentage and grafting efficiency were examined. The grafting percentage and grafting efficiency in optimum conditions were found to be 301.06 % and 55.35 %, respectively. The structures of sodium alginate-graft-poly(N,N-diethylacrylamide) copolymers were characterized by ATR-FTIR, Raman, 1H-NMR, 13C-NMR, DSC, TGA and GPC analyses. Thermal stability of synthesized copolymers was found higher than that of NaAlg. Copolymers characterized were used in oral microspheres application of 5-Fluorouracil (5-FU). Sodium alginate-graft-poly(N,N-diethylacrylamide) microspheres were prepared by crosslinking with glutaraldehyde in hydrochloric acid medium. Drug loaded microspheres were characterized with entrapment efficiency and particles size. Swelling degrees of empty microspheres were carried out at different pH and temperature. Effect of grafting yield, polymer concentration, drug/polymer ratio, crosslinking agent concentration, crossslinking time, pH and temperature on release of drug from microspheres were examined. 5-FU release from microspheres with 20 grafting percentage decreased from 95 to 75 with increasing temperature from 25 ºC to 37 ºC while release from microspheres with 110 grafting percentage decreased from 75 to 43. Release behavior and swelling degree of microspheres showed that obtained microspheres are thermoresponsive and be able to control the drug release. Chemical stability of drug in the microspheres was confirmed by ATR-FTIR measurements. DSC result showed that glass transition temperature increases with drug loading and XRD results demonstrated drug exist in crystaline structure. The surface morphology was investigated with SEM and AFM analysis. Kinetic parameters were determined by using release results. The diffusion coefficients were calculated for the transport of drug trought the polymeric microspheres and the results were found in accordance with the release results. It was shown that diffusion coefficients decreased with increasing glutaraldehyde concentration, HCI concentration, crosslinking time to glutaraldehyde.
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Kimya, Chemistry, , , , , , , ,
