Anti-kanser ilacı 5-Fluorourasil'in bentonit yüklü kitosan/hidroksipropil metilselüloz biyonanokompozit filmlerden kontrollü salımı

Year 2022, IOCENS’21 Konferansı Ek Sayısı, 1 - 10, 30.09.2022

Mürit Akal Muhammed Emre Demirdere Derya Ünlü

https://doi.org/10.17714/gumusfenbil.1005732

Abstract

Kontrollü salım, geleneksel tedavinin aksine, bir maddenin bir ortamdaki derişimini belirli bir süre boyunca korumak için kademeli olarak bir sistemden serbest bırakılması anlamına gelmektedir. İlaç salım sistemlerinde ilacın hastalıklı bölgeye kontrollü bir şekilde salımı, tedavi ve toksisite açısından önem arz etmektedir. Özellikle 5-Fluorourasil (5-FU) gibi toksik özelliği fazla olan ilaçlar kontrollü ilaç salım teknolojisinde özel yere sahiptir. Tedavinin başarılı bir şekilde yapılabilmesi için 5-FU gibi antikanser ilaçlarının olası yan etkilerini ortadan kaldırmak ve tedavi edici etkisini arttırmak için kontrollü ilaç salım sistemlerinin geliştirilmesi önem kazanmaktadır. Bu çalışmanın amacı, 5-FU'in kontrollü salımı için biyolojik olarak parçalanabilen ve biyouyumlu özgün bir biyonanokompozit film geliştirmektir. Bu amaçla bentonit yüklü kitosan hidroksipropil metilselüloz biyonanokompozit filmler çözeltiden döküm ve solvent buharlaştırma tekniği kullanılarak sentezlenmiştir. Biyonanokompozit filmlerin kimyasal bağ yapısı, bentonit ilavesinin yapıdaki amin ve hidroksil gruplarına etkisi Fourier dönüşümlü kızılötesi ile belirlenmiştir. Polimerlerin ve bentonitin morfolojik özellikleri ve uyumluluğu, taramalı elektron mikroskobu kullanılarak karakterize edilmiştir. Biyonanokompozit filmlerin sorpsiyon derecesi şişme testleri ile değerlendirilmiştir. Nanokompozit filmdeki bentonit içeriğinin %5'ten %25'e artması ile sorpsiyon derecesi %2.99'dan % 65.05'e artmıştır. Ayrıca sentezlenen biyonanokompozit filmlere bentonit ilavesinin ve pH'ın 5-FU'in yüklenmesi ve enkapsülasyon verimliliği üzerindeki etkileri araştırılmıştır. 5-FU yüklenen nanokompozit filmlerden ilacın kontrollü salım çalışmaları yapılmıştır. Elde edilen sonuçlar, nanokompozit ilaç taşıyıcı filmlerde bentonit kullanımının kapsülleme verimliliğini ve salım özelliklerini geliştirdiğini göstermiştir. %5 bentonit yüklü filmde dört günün sonunda pH=7.4'te %40.12 salım değeri elde edilmiştir.

Keywords

Bentonit, Fluorourasil, Hidroksipropil metilselüloz, İlaç salımı, Kitosan, Nanokompozit film

Supporting Institution

Tübitak

Project Number

1919B012003589

Thanks

Bu çalışma TÜBİTAK tarafından 2209-A Üniversite Öğrencileri Araştırma Projeleri Destekleme Programı kapsamında desteklenmiştir.

Controlled release of the anti-cancer drug 5-Fluorouracil from bentonite-loaded chitosan/hydroxypropyl methylcellulose bionanocomposite films

Abstract

Controlled release, on the contrary traditional treatment, means the gradual release of a substance from a system in order to maintain its concentration in a medium over a period of time. In drug release systems, the controlled release of the drug to the diseased area has importance in terms of treatment and toxicity. Especially drugs with high toxic properties such as 5-Fluorouracil (5-FU) have an important place in controlled drug release technology. In order to complete the treatment successfully, it is important to develop controlled drug release systems to eliminate the possible side effects of anticancer drugs such as 5-FU and to increase the therapeutic effect. The aim of this study is to develop a unique biodegradable and biocompatible bionanocomposite film for the controlled release of 5-FU. For this purpose, bentonite loaded chitosan hydroxypropyl methylcellulose bionanocomposite films were synthesized using solution casting and solvent evaporation techniques. The chemical bond structure of the bionanocomposite films and the effect of bentonite addition on the amine and hydroxyl groups in the structure were determined by Fourier transform infrared. Morphological properties and compatibility of polymers and bentonite were characterized by using scanning electron microscopy. The degree of sorption of the bionanocomposite films was evaluated by swelling tests. As the bentonite content in the nanocomposite film increased from 5% to 25%, the sorption degree of film increased from 2.99% to 65.05%. In addition, the effects of bentonite addition of the synthesized bionanocomposite films and pH of medium on the 5-FU loading and encapsulation efficiency were investigated. Controlled release studies were carried out by using 5-FU loaded nanocomposite films. The obtained results showed that the usage of bentonite in nanocomposite drug carrier films were improved the release properties. After four days, a release value was obtained as 40.12% at pH=7.4 in the 5 wt. % bentonite loaded films.

Keywords

Bentonite, Fluorouracil, Hydroxypropyl methylcellulose, Drug release, Chitosan, Nanocomposite film

Project Number

1919B012003589

References

• Abukhadra, M.R., Mohamed, A. S., El-Sherbeeny, A. M., Nadeem, A., & Ahmad, S. F. (2020). Synthesis of exfoliate bentonite/cellulose nanocomposite as a delivery system for Oxaliplatin drug with enhanced loading and release properties; cytotoxicity and pharmacokinetic studies. Chemical Physics Letters, 755, 137818. https://doi.org/10.1016/j.cplett.2020.137818
• Amini-Fazl, M. S., Mohammadi, R., & Kheiri, K. (2019). 5‑Fluorouracil loaded chitosan/polyacrylic acid/Fe3O4 magnetic nanocomposite hydrogel as a potential anticancer drug delivery system. International Journal of Biological Macromolecules, 132, 506–513. https://doi.org/10.1016/j.ijbiomac.2019.04.005
• 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. https://doi.org/10.1016/j.ijpharm.2018.12.011
• Gu, C., Le, V., Lang, M., & Liu, J. (2014). Preparation of polysaccharide derivates chitosan-graft-poly(ɛ-caprolactone) amphiphilic copolymer micelles for 5-fluorouracil drug delivery. Colloids and Surfaces B: Biointerfaces, 116, 745–750. https://doi.org/10.1016/j.colsurfb.2014.01.026
• He, T., Wang, W., Chen, B., Wang, J., Liang, Q., & Chen, B. (2020). 5-Fluorouracil monodispersed chitosan microspheres: microfluidic chip fabrication with crosslinking, characterization, drug release and anticancer activity. Carbohydrate Polymers, 236, 116094. https://doi.org/10.1016/j.carbpol.2020.116094
• Justin, R., & Chen, B. (2014). Characterisation and drug release performance of biodegradable chitosan–graphene oxide nanocomposites. Carbohydrate Polymers, 103, 70–80. https://doi.org/10.1016/j.carbpol.2013.12.012
• Kulkarni, A.R., Soppimath, K.S., Aminabhavi, T., Dave, A.M., & Mehta, H.M. (2000). Glutaraldehyde crosslinked sodium alginate beads containing liquid pesticide for soil application. Journal of Controlled Release, 63, 97-105. https://doi.org/10.1016/S0168-3659(99)00176-5
• Lei, L., Liu, X., Guo, S., Tang, M., Cheng, L., & Tian, L. (2010). 5-Fluorouracil-loaded multilayered films for drug controlled releasing stent application: Drug release, microstructure, and ex vivo permeation behaviors. Journal of Controlled Release, 146(1), 45–53. https://doi.org/10.1016/j.jconrel.2010.05.017
• McCarron, P. A., Woolfson, A. D., & Keating, S. M. (2000). Sustained Release of 5-Fluorouracil from Polymeric Nanoparticles. Journal of Pharmacy and Pharmacology, 52(12), 1451–1459. https://doi.org/10.1211/0022357001777658
• Pingping, S., Yuying, W., Xueming, Z., Zhongya, Y., Meng, W., & Feng, Xu. (2018). Preparation of Covalently Crosslinked Sodium Alginate/Hydroxypropyl Methylcellulose pH-Sensitive Microspheres for Controlled Drug Release, BioResources, 13(4), 8614-8628.
• Reddy, A. B., Manjula, B., Jayaramudu, T., Sadiku, E. R., Anand Babu, P., & Periyar Selvam, S. (2016). 5-Fluorouracil Loaded Chitosan–PVA/Na+MMT Nanocomposite Films for Drug Release and Antimicrobial Activity. Nano-Micro Letters, 8(3), 260–269. https://doi.org/10.1007/s40820-016-0086-4
• Sakr, M. A., Mohamed, M.G.A., Wu, R., Shin, S.R., Kim, D., Kim, K., & Siddiqua, S. (2020). Development of bentonite-gelatin nanocomposite hybrid hydrogels for tissue engineering. Applied Clay Science, 199, 105860. https://doi.org/10.1016/j.clay.2020.105860
• Shu, X.Z., & Zhu K.J. (2002). The influence of multivalent phosphate structure on the properties of ionically cross-linked chitosan films for controlled drug release. European Journal of Pharmaceutics and Biopharmaceutics, 54(2), 0–243. https://doi.org/10.1016/S0939-6411(02)00052-8
• 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. https://doi.org/10.1016/S0169-409X(01)00112-0
• Sun, L., Chen, Y. Zhou, Y. et al. (2017). Preparation of 5-fluorouracil-loaded chitosan nanoparticles and study the sustained release in vitro and in vivo. Asian Journal of Pharmaceutical Sciences, 12(5), 418-423. https://doi.org/10.1016/j.ajps.2017.04.002
• 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. https://doi.org/10.1016/j.jcis.2018.01.073
• Zhang, H., Shi, Y., Xu, X., Zhang, M., & Ma, L. (2020). Structure Regulation of Bentonite-Alginate Nanocomposites for Controlled Release of Imidacloprid. ACS Omega. 5(17), 10068–10076. https://doi.org/10.1021/acsomega.0c00610