Grafen Oksit Katkılı Kitosan/Hidroksipropil Metilselüloz Biyonanokompozit Film Sentezi ve Anti-Kanser İlacı 5-Fluorourasil'in Kontrollü Salımında Kullanımı
Abstract
Kontrollü ilaç salım sistemleri, kullanılan ilaç miktarını en aza indirmek, ilaç alma periyodunu uzatmak, tedavi sırasında oluşabilecek yan etkileri ortadan kaldırmak amacıyla son yıllarda oldukça ilgi görmektedir. İlaç salımının kullanılmasının temel nedeni daha etkili bir tedavi yöntemi sağlamaktır. Bu çalışmada kontrollü ilaç salımı için biyonanokompozit filmler sentezlenmiştir. Biyotemelli polimerler olarak kitosan ve hidroksipropil metil selüloz kullanılmıştır. Grafen oksit ilave edilerek katkılandırılan filmlere ilaç yüklemesi yapılarak salım performansları incelenmiştir. Model ilaç olarak antikanser ilacı 5-Fluorourasil (5-Fu) seçilmiştir. Sentezlenen filmlerin kimyasal bağ yapıları Fourier dönüşümlü kızılötesi (FTIR) ile belirlenmiştir. Polimerlerin birbiri ile uyumu, karışabilirliği, eklenen katkının dağılımı taramalı elektron mikroskobu (SEM analizi) ile görüntülenmiştir. İlaç salımında filmlerin şişme derecesi önemli olduğu için suda şişme testleri yapılmıştır. Grafen oksit miktarı arttıkça başlangıçta şişme derecesi artmış ardından düşme eğilimi göstermiştir. %20 grafen oksit katkılı kitosan/hidroksipropil metilselüloz biyonanokompozit filmde %321.68 şişme derecesi gözlenirken, %30 grafen oksit katkılı kitosan/hidroksipropil metilselüloz biyonanokompozit filmde %248.95 şişme derecesi göstermiştir. İlaç tutuklama verimi grafen oksit miktarı arttıkça çok az artış göstermiştir. En yüksek ilaç tutuklama verimi 12 saatin sonunda %30 grafen oksit katkılı kitosan/hidroksipropil metilselüloz biyonanokompozit filmde %69.90 olarak elde edilmiştir. Aynı özellikteki filmde ilaç salım yüzdesi de 4 günün sonunda %9.87 olarak elde edilmiştir. İlaç salımına ortam pH'ının etkisi incelendiğinde en iyi ilaç salım ortamının pH=7.4 olduğu görülmüştür. Elde edilen sonuçlar sentezlenen filmlerin geliştirilebilir olduğunu grafen oksit miktarının arttırılarak ilaç salım yüzdesinin arttırılabileceğini göstermiştir.
Supporting Institution
Tübitak
Project Number
1919B012003589
Thanks
Bu çalışma, TÜBİTAK tarafından 2209-A projesi kapsamında maddi olarak desteklenmiştir.
References
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- Lin, Y.K., Nguyen, V.H., Yu, J. C.C., Lee, C.W., Deng, Y.H., Wu, J. C. S., Chen, C.L. (2017). Biodiesel production by pervaporation-assisted esterification and pre-esterification using graphene oxide/chitosan composite membranes. Journal of the Taiwan Institute of Chemical Engineers, 79, 23–30.
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- Pingping, S., Yuying, W., Xueming, Z., Zhongya, Y., Meng, W., Feng, X. (2018). Preparation of Covalently Crosslinked Sodium Alginate/Hydroxypropyl Methylcellulose pH-Sensitive Microspheres for Controlled Drug Release. BioResources, 13, 8614-8628.
- Siepmann, J., Peppas, N.A. (2012). Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Advanced Drug Delivery Reviews, 64, 163–174.
- Reddy, A., Babul, M.B., Jayaramudu, T., Sadiku, E. R., Anand, B.P., Periyar, S.S. (2016). 5-Fluorouracil Loaded Chitosan–PVA/Na+MMT Nanocomposite Films for Drug Release and Antimicrobial Activity. Nano-Micro Letters, 8, 260–269.
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- Wang, C., Zhang, Z., Chen, B., Gu, L., Li, Y., Yu, S. (2018). Design and evaluation of galactosylated chitosan/graphene oxide nanoparticles as a drug delivery system. Journal of Colloid and Interface Science. 516, 332–341.
- Wang, J., Liu, C., Shuai, Y., Cui, X., Nie, L. (2014). Controlled release of anticancer drug using graphene oxide as a drug-binding effector in konjac glucomannan/sodium alginate hydrogels. Colloids and Surfaces B: Biointerfaces, 113, 223–229.
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Synthesis of Graphene Oxide Loaded Chitosan/ Hydroxypropyl Methylcellulose Bionanocomposite Films and Usage of Controlled Release of Anti-Cancer Drug 5- Fluorouracil
Abstract
Controlled drug release systems have attracted a lot of attention in recent years in order to minimize the amount of drug used, to extend the period of taking drugs, and to eliminate the side effects that may occur during treatment. The main aim for using drug release is to provide a more effective treatment method. In this study, bionanocomposite films were synthesized for controlled drug release. Chitosan and hydroxypropyl methyl cellulose were used as biobased polymers. The release performances of graphene oxide loaded films were investigated by drug loading on the films. The anticancer drug 5-Fluorouracil was chosen as the model drug. Chemical bond structures of the synthesized films were determined by Fourier transform infrared (FTIR). Compatibility, miscibility and distribution of the added additives were observed by scanning electron microscopy (SEM analysis). The water swelling tests were performed because of the importanece of the degree of swelling of the films in drug release. As the amount of graphene oxide increased, the degree of swelling initially increased and then tended to decrease. While a swelling degree of 321.68% was observed in the 20% graphene oxide loaded chitosan/hydroxypropyl methylcellulose bionanocomposite film, it was 248% in the 30% graphene oxide loaded chitosan/hydroxypropyl methylcellulose bionanocomposite film. The drug encapsulation efficiency increased slightly as the amount of graphene oxide increased. The highest drug encapsulation efficiency was obtained as 69.90% in 30% graphene oxide loaded chitosan hydroxypropyl methylcellulose bionanocomposite film at the end of the 12 hours. The percentage of drug release in the same film was obtained as 9.87% at the end of 4 days. The best drug release medium was determined as pH=7.4. The results obtained showed that the synthesized films could be improved and the percentage of drug release could be increased by increasing the amount of graphene oxide.
Project Number
1919B012003589
References
- Arias, J.L., Ruiz, M.A., López-Viota, M., Delgado, A.V. (2008). Poly(alkylcyanoa- crylate) colloidal particles as vehicles forantitum our drug delivery:a comparative study. Colloids and Surfaces B: Biointerfaces, 62, 64-70.
- Arruda, M. N., Souza, C. B., Eugênio, K. F. R., De, M. S., Gonçalves, E. S. (2020). Influence of swelling level on charge transmission of chitosan and reduced graphene oxide film electrodes. Materials Chemistry and Physics, 255, 123623.
- Azhar, F.F., A. Olad, (2014). A study on sustained release formulations for oral delivery of 5-fluorouracil based on alginate–chitosan/montmorillonite nanocomposite systems. Applied Clay Science, 101, 288-296.
- Calvo, N. L., Svetaz, L. A., Alvarez, V.A., Quiroga, A. D., Lamas, M. C., Leonardi, D. (2018). Chitosan-hydroxypropyl methylcellulose tioconazole films: A promising alternative dosage form for the treatment of vaginal candidiasis. International Journal of Pharmaceutics, 556, 181-191.
- Duman, S.S., Şenel, S. (2004). Kitosan ve veteriner alandaki uygulamaları, Veteriner Cerrahi Dergisi, 10, 62-72.
- Jafari, Z., Rad, A.S., Baharfar, R., Asghari, S., Esfahani, M.R. (2020). Synthesis and application of chitosan/tripolyphosphate/graphene oxidehydrogel as a new drug delivery system for Sumatriptan Succinate. Journal of Molecular Liquids, 315, 113835.
- Lin, Y.K., Nguyen, V.H., Yu, J. C.C., Lee, C.W., Deng, Y.H., Wu, J. C. S., Chen, C.L. (2017). Biodiesel production by pervaporation-assisted esterification and pre-esterification using graphene oxide/chitosan composite membranes. Journal of the Taiwan Institute of Chemical Engineers, 79, 23–30.
- Özkan, M.Ç. (2012). Topikal 5-Fluorourasil Uygulamasının Epinörektomi Yapılan Sıçan Siyatik Sinir Çevresinde Skar Dokusu Oluşumu Üzerine Etkisinin Araştırılması, Uzmanlık Tezi, Uludağ Üniversitesi, Bursa, Türkiye.
- Pingping, S., Yuying, W., Xueming, Z., Zhongya, Y., Meng, W., Feng, X. (2018). Preparation of Covalently Crosslinked Sodium Alginate/Hydroxypropyl Methylcellulose pH-Sensitive Microspheres for Controlled Drug Release. BioResources, 13, 8614-8628.
- Siepmann, J., Peppas, N.A. (2012). Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Advanced Drug Delivery Reviews, 64, 163–174.
- Reddy, A., Babul, M.B., Jayaramudu, T., Sadiku, E. R., Anand, B.P., Periyar, S.S. (2016). 5-Fluorouracil Loaded Chitosan–PVA/Na+MMT Nanocomposite Films for Drug Release and Antimicrobial Activity. Nano-Micro Letters, 8, 260–269.
- Veerapur, R. S., Gudasi, K. B., Aminabhavi, T. M. (2007). Pervaporation dehydration of isopropanol using blend membranes of chitosan and hydroxypropyl cellulose. Journal of Membrane Science, 304, 102–111.
- Wang, C., Zhang, Z., Chen, B., Gu, L., Li, Y., Yu, S. (2018). Design and evaluation of galactosylated chitosan/graphene oxide nanoparticles as a drug delivery system. Journal of Colloid and Interface Science. 516, 332–341.
- Wang, J., Liu, C., Shuai, Y., Cui, X., Nie, L. (2014). Controlled release of anticancer drug using graphene oxide as a drug-binding effector in konjac glucomannan/sodium alginate hydrogels. Colloids and Surfaces B: Biointerfaces, 113, 223–229.
- Wang, G., Chen, G., Wei, Z., Dong, X., Qi, M. (2013). Multifunctional Fe3O4/graphene oxide nanocomposites for magnetic resonance imaging and drug delivery, Materials Chemistry and Physics, 141, 997–1004.
- Yalçın, A. (2011). Manyetik alana duyarlı jelatin - hidrojellerin hazırlanması ve ilaç salımı profilinin incelenmesi, Yüksek Lisans Tezi, İstanbul Üniversitesi, İstanbul, Türkiye. Zhang, N., Yin, Y., Xu, S.J., Chen, W.S. (2008). 5-Fluorouracil:mechanisms of resistance and reversal strategies. Molecules, 13, 1551-1569.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Engineering |
| Journal Section | Articles |
| Authors | |
| Project Number | 1919B012003589 |
| Publication Date | November 30, 2021 |
| Published in Issue | Year 2021 Issue: 28 |
