Biyouyumlu Kolajen /PVA /TiO2 Nanokompozit Filmlerden 5-FU Kanser İlacının Salımı

Abstract

Bir ilaç salım sistemi, verimliliği ve güvenliği artırmak için salım hızını, miktarını, zamanını ve yerini kontrol edebilen terapötik bir maddenin vücudumuza girmesine yönelik bir formülasyondur. İlaç salım sistemlerinde kullanılacak olan materyalin iyi bir biyouyumluluğa sahip olması, toksik ve zararlı maddeler içermemesi gerekmektedir Bu çalışmada, biyouyumlu poli(vinil alkol)/kolajen/TiO2 (PVA/Col/TiO2) membranları döküm yöntemi ile hazırlanmıştır. Membranların 5-florourasil (5-FU) kanser ilacı etken maddesinin in vitro çalışması franz difüzyon hücreleri ile değerlendirilmiştir. Hazırlanan membranların çapraz bağlaması, yeşil bir çapraz bağlayıcı sitrik asitin ile gerçekleştirildi. Membranlar diferansiyel tarama kalorimetresi (DSC) ve X Işını Kırınım (XRD) analiz yöntemleri ile gerçekleştirildi. Hazırlanan membranlarda Col : PVA karışım oranı, Membran kalınlığının ve sıcaklığın membranlardan 5-FU salımı üzerindeki etkileri incelendi. 5-FU salımında hazırlanan membranlarda en iyi aktarımın PVA/Col/TiO2 (4:4) membranlarında %90,3 (m/m) olarak elde edildiği ve artan membran kalınlığı ile 5-FU salımının azaldığı görülmüştür. Bu çalışma ile hazırlanan kompozit membranların, doğa dostu ve uzun süreli tedavisi olan kanser için, kanser ilaçlarının salımında kullanılabilecek umut verici bir materyal olabileceği düşünülmektedir.

Keywords

• Biyobozunur Kompozit Membran
• Yeşil Çapraz Bağlayıcı
• Franz Difüzyon

Release of 5-FU Cancer Drug from Biocompatible Collagen/PVA/TiO2 Nanocomposite Films

Abstract

A drug delivery system is a formulation for introducing a therapeutic agent into the body to control the release rate, amount, time, and location to increase efficiency and safety. The material used in drug delivery systems should have good biocompatibility and not contain toxic and harmful substances. In this study, biocompatible poly(vinyl alcohol)/collagen/TiO2 (PVA/Col/TiO2) membranes were prepared using the casting method. In vitro study of 5-fluorouracil (5-FU), a cancer drug active substance, of the membranes was evaluated with Franz diffusion cells. The prepared membranes were cross-linked with a green cross-linker, citric acid. Membranes were performed using differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis methods. The effects of Col: PVA mixing ratio, membrane thickness, and temperature on 5-FU release from the membranes were investigated. It was observed that the best transfer in the prepared membranes for 5-FU release was obtained as 90.3% (m/m) in PVA/Col/TiO2 (4:4) membranes, and 5-FU release decreased with increasing membrane thickness. It is thought that the composite membranes prepared in this study can be a promising material that can be used in the release of cancer drugs for cancer, which has an environmentally friendly and long-term treatment.

Keywords

• Biodegradable Composite Membrane
• Green Crosslinker
• Franz Diffusion

References

1. [1] Sanson A L, Silva S C R, Martins M C G, Giusti-Paiva A, Maia P P, Martins I. Liquid-liquid extraction combined with high performance liquid chromatography-diode array-ultra-violet for simultaneous determination of antineoplastic drugs in plasma. Brazilian Journal of Pharmaceutical Sciences. 2011; 47: 363-371.
2. [2] Saif M W, Choma A, Salamone S J, Chu E. Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes. JNCI: Journal of the National Cancer Institute. 2009; 101: 1543-1552.
3. [3] Paradossi G, Cavalieri F, Chiessi E, Spagnoli C, Cowman M K. Poly(vinyl alcohol) as versatile biomaterial for potential biomedical Application. Journal of Materials Science: Materials in Medicine. 2003; 14: 687-691.
4. [4] Khan M A, Bhattacharia S K, Kader M A, Bahari K. Preparation and characterization of ultra violet (UV) radiation cured bio-degradable films of sago starch/PVA blend. Carbohydrate Polymers. 2006; 63: 500-506.
5. [5] Sarti B, Scandola M. Viscoelastic and thermal properties of collagen/poly(vinyl alcohol) blends. Biomaterials. 1995; 16: 785-792.
6. [6] Sionkowska A, Wisniewski M, Skopinska J. Photochemical stability of collagen/poly (vinyl alcohol) blends. Polymer Degradation and Stability. 2004; 83:117- 125.
7. [7] Chen C H, Wang F Y, Mao CF, Liao WT, Hsieh C D. Studies of chitosan: II. Preparation and characterization of chitosan/poly(vinyl alcohol)/ gelatin ternary blend films. International Journal of Biological Macromolecules. 2008; 43: 37-42.
8. [8] Lee K H, Baek D H, Ki C S, Park Y H. Preparation and characterization of wet spun silk fibroin/poly(vinyl alcohol) blend filaments. International Journal of Biological Macromolecules. 2007; 41: 168-172.

9. [9] Fernandes D M, Winkler Hechenleitner A A, Job A E, Radovanocic E, Gómez Pineda E A. Thermal and photochemical stability of poly(vinyl alcohol)/modified lignin blends. Polymer Degradation and Stability. 2006; 91: 1192-1201.
10. [10] Van der Rest R, Garrone M. Collagen family of proteins, The FASEB journal. 1991; 5: 2814-2819.
11. [11] Sionkowska A, Kamińska A, Miles C A, Bailey A J. The effect of UV radiation on the structure and properties of collagen. Polimery. 2001; 6: 379– 452.
12. [12] Huc A. Collagen biomaterials characteristics and applications. Journal of the American Leather Chemists Association. 1985; 80: 195-212.
13. [13] Sionkowska A, Skopińska J, Wisniewski M. Photochemical stability of collagen/poly (vinyl alcohol) blends. Polymer Degradation and Stability. 2004; 83:117-125.
14. [14] Leng Q, Li Y, Pang X, Wang B, Wu Z, Lu Y, ... & Fu S. Curcumin nanoparticles incorporated in PVA/collagen composite films promote wound healing. Drug delivery. 2020; 27(1): 1676-1685.
15. [15] Karthick S A, Ragavi T K, Naresh K, & Sreekanth P R. A study on collagen-PVA and chitosan-PVA nanofibrous matrix for wound dressing application. Materials Today: Proceedings. 2022; 56: 1347-1350.
16. [16] Armentano I, Dottori M, Fortunati E, Mattioli S, Kenny J M. Biodegradable polymer matrix nanocomposites for tissue engineering: a review. Polymer degradation and stability. 2010; 95: 2126-2146.
17. [17] Yun Y H, Yun J W, Yoon S D, Byun H S. Physical properties and photocatalytic activity of chitosan-based nanocomposites added titanium oxide nanoparticles. Macromolecular Research. 2016; 24: 51-59.
18. [18] Chaudhari S, Shaikh T, Pandey P. A review on polymer TiO2 nanocomposites. International Journal of Engineering Research and Applications. 2013; 3: 1386-1391.
19. [19] Mallakpour S, Barati A. Optically active poly (amide-imide)/TiO2 bionanocomposites containing L-isoleucine amino acid moieties: synthesis, nanostructure and properties. Polymer-Plastics Technology and Engineering. 2013; 52: 997-1006.
20. [20] Çakıcı G T. Preparation and characterization of biocompatible membranes based on TiO2 nanoparticul. Sakarya University Journal of Science. 2021; 25: 1376-1385.
21. [21] Oryan A, Kamali A, Moshiri A, Baharvand H, Daemi H. Chemical crosslinking of biopolymeric scaffolds: Current knowledge and future directions of crosslinked engineered bone scaffolds. International Journal of Biological Macromolecules. 2018; 107: 678-688.
22. [22] Musetti A, Paderni K, Fabbri P, Pulvirenti A, Al‐Moghazy M, Fava P. Poly (vinyl alcohol)‐based film potentially suitable for antimicrobial packaging applications. Journal of Food Science. 2014; 79: E577-E582.
23. [23] Tripathi S, Mehrotra G K, & Dutta P K. Chitosan–silver oxide nanocomposite film: Preparation and antimicrobial activity. Bulletin of Materials Science. 2011; 34(1): 29–35.
24. [24] Kahraman E, Hayri-Senel T, & Nasun-Saygili G. Kinetics and optimization studies of controlled 5-fluorouracil release from graphene oxide incorporated vegetable oil-based polyurethane composite film. ACS omega. 2024; 9(48): 47395-47409.
25. [25] Taşkın Çakıcı G. Nano TiO2-doped sodium alginate/hydroxypropyl methylcellulose synthesis of bionanocomposite membrane and its use in controlled release of anti-cancer drug 5-fluorouracil. Polymer Bulletin. 2023; 80: 12719-12740.
26. [26] Samouillan V, Delaunay F, Dandurand J, Merbahi N, Gardou J P, Yousfi M, Lacabanne C. The use of thermal techniques for the characterization and selection of natural biomaterials. Journal of Functional Biomaterials. 2011; 2:230-248.
27. [27] Betzabe Gonzalez‐Campos J, Garcia‐Carvajal Z Y, Prokhorov E, Luna‐Barcenas J G, Mendoza‐Duarte, M E, Lara‐Romero J, Sanchez I C. Revisiting the thermal relaxations of poly (vinyl alcohol). Journal of Applied Polymer Science. 2012; 125: 4082-4090.
28. [28] Kuo S W, Chang F C. Miscibility and hydrogen bonding in blends of poly (vinylphenol-co-methyl methacrylate) with poly (ethylene oxide). Macromolecules. 2001; 34: 4089-4097.
29. [29] Luo Y B, Li W D, Wang X L, Xu D Y, Wang Y Z. Preparation and properties of nanocomposites based on poly (lactic acid) and functionalized TiO2. Acta Materialia. 2009; 57: 3182-3191.
30. [30] Alghamdi H M, Rajeh A. Synthesis of carbon nanotubes/titanium dioxide and study of its effect on the optical, dielectric, and mechanical properties of polyvinyl alcohol/sodium alginate for energy storage devices. International Journal of Energy Research. 2022; 46: 20050 –20066.
31. [31] Yu G, Yang C, Dan N, Dan W, Chen Y. Polyglutamic acid grafted dopamine modified collagen-polyvinyl alcohol hydrogel for a potential wound dressing. Designed Monomers and Polymers. 2021; 24: 293-304.
32. [32] Shaari N, Kamarudin S K, Zakaria Z. Potential of sodium alginate/titanium oxide biomembrane nanocomposite in DMFC application. International Journal of Energy Research. 2019; 43: 8057-8069.
33. [33] Zhao J, Yao L, Nie S, Xu Y. Low-viscosity sodium alginate combined with TiO2 nanoparticles for improving neuroblastoma treatment. International Journal of Biological Macromolecules. 2021; 167: 921-933.
34. [34] Uzun İ. Methods of determining the degree of crystallinity of polymers with X-ray diffraction: a review. Journal of Polymer Research. 2023; 30(10): 394.
35. [35] Otitoju T A, Ahmadipour M, Li S, Shoparwe N F, Jie L X, Owolabi A L. Influence of nanoparticle type on the performance of nanocomposite membranes for wastewater treatment. Journal of Water Process Engineering. 2020; 36:101356
36. [36] Huang R Y M, Yeom C K. Pervaporation separation of aqueous mixtures using crosslinked polyvinyl alcohol membranes. III. Permeation of acetic acid-water mixtures. Journal of Membrane Science. 1991; 58: 33-47.
37. [37] Keleş D, Balcı D, Taşdemir M, Ulutaş E. Polipropilen + %20 Kenevir Takviyeli / Çörek Otu / Maleik Anhidrit Aşılı Polipropilen Polimer Kompozitinin Fiziksel Özelliklerinin İncelenmesi. Gazi Üniversitesi Fen Bilimleri Dergisi Part C: Tasarım ve Teknoloji. 2024; 12: 464-474.