بررسی رهایش داروهای ضد سرطان متوتروکسات و 5- فلوئوروراسیل از ساختار چندلایه نانولیفی پلی‌کاپرولاکتون: کیتوسان

نویسندگان

1 1- دانشکده مهندسی نساجی، دانشگاه صنعتی اصفهان، ایران، اصفهان 83111-84156

2 2- دانشگاه علوم پزشکی تهران، مرکز تحقیقات سرطان، ایران، تهران 53761-14176

چکیده

در این پژوهش، ساختارهای هفت‌لایه نانولیفی از پلیمرهای پلی‌کاپرولاکتون: کیتوسان حاوی دو داروی ضدسرطان متوتروکسات و 5- فلوئوروراسیل، به‌منظور رهایش کنترل‌شده دارو، تولید و ارزیابی شد. برای این منظور، لایه‌های دوم، چهارم و ششم حاوی دارو مابین لایه‌های فاقد دارو قرار گرفتند. مورفولوژی سطح و ساختار شیمیایی نانوالیاف فاقد دارو و حاوی دارو به‌ترتیب به‌کمک میکروسکوپ الکترونی روبشی و طیف‌سنجی مادون ‌قرمز ارزیابی شد. نرخ رهایش دارو در محلول بافر فسفات سالین (4/7=pH) و غلظت داروی آزادشده با استفاده از روش اسپکتروفتومتری محاسبه شد. خواص مکانیکی نمونه‌های تک و چندلایه نیز اندازه‌گیری شد. تصاویر میکروسکوپ الکترونی روبشی تولید الیاف یکنواخت و بدون دانه را نشان داد. طیف مادون‌قرمز نمونه‌ها حضور دارو در مخلوط پلیمری بدون هیچ نوع برهم‌کنشی را تأیید کرد. نتایج حاکی از آن بود که با افزایش مقدار کیتوسان، ساختاری شکننده تشکیل شده و درصد ازدیاد طول کاهش می‌یابد. رهایش دو داروی متوتروکسات و 5- فلوئوروراسیل در محیط خنثی به‌مدت 26 روز بررسی شد و نتایج بیانگر یک رهایش آرام و پایدار بود.

کلیدواژه‌ها

عنوان مقاله [English]

Investigating the Release of Methotrexate and 5-Fluorouracil Anticancer Drugs from Multi-Layered Nanofiber Structure of Polycaprolactone/Chitosan

نویسندگان [English]

  • N. Poursharifi 1
  • D. Semnani 1
  • P. Soltani 1
  • S. Amanpour 2
1 1- Department of Textile Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran.
2 2- Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran 14176-53761, Iran.
چکیده [English]

In this study, seven-layer nanofiber structures consisting of polycaprolactone/ chitosan polymers loaded with methotrexate and 5-fluorouracil anti-cancer drugs, for controlled drug delivery, were produced and evaluated. For this purpose, the second, fourth and sixth layers were loaded with drug and placed between the drug-free layers. The surface morphology of drug-free and drug-loaded nanofibers was investigated by scanning electron microscopy (SEM) and Fourier transform infrared spectrometry (FTIR) was used to study their chemical structure. The drug release rate in phosphate buffered saline (pH=7.4) and the released drug concentration were measured by spectrophotometry. Mechanical properties of single- and multi-layered samples were also investigated. SEM images showed formation of uniform and beadless fibers. FTIR spectrum confirmed presence of the drugs in the polymer mixture with no interaction. It was found that by increasing the chitosan content, a brittle structure with decreased elongation is formed. The release behavior of methotrexate and 5-Fluoracil drugs in neutral pH environment for 26 days was evaluated and the results exhibited a slow and sustained release.

کلیدواژه‌ها [English]

  • Drug delivery
  • Nanofibers
  • Polycaprolactone
  • Chitosan
  • 5-Fluorouracil
  • Methotrexate

مراجع

1. Brouwers, J., “Advanced and Controlled Drug Delivery Systems in Clinical Disease Management”, Pharmacy World and Science, Vol. 18, pp. 153-162, 1996.
2. Soppimath, K. S., Aminabhavi, T. M., Kulkarni, A. R., and Rudzinski, W. E., “Biodegradable Polymeric Nanoparticles as Drug Delivery Devices”, Journal of Controlled Release, Vol. 70, pp. 1-20, 2001.
3. Yoo, H. S., and Park, T. G., “Folate Receptor Targeted Biodegradable Polymeric Doxorubicin Micelles”, Journal of Controlled Release, Vol. 96, pp. 273-283, 2004.
4. Newkome, G. R., Moorefield, C. N., and Vögtle, F., Dendrimers and Dendrons: Concepts, Syntheses, Applications, Wiley-VCH Verlag GmbH, 2001.
5. Zasadzinski, J. A., Wong, B., Forbes, N., Braun, G., and Wu, G., “Novel Methods of Enhanced Retention in and Rapid, Targeted Release from Liposomes”, Current Opinion in Colloid & Interface Science, Vol. 16, pp. 203-214, 2011.
6. Hoare, T. R., and Kohane, D. S., “Hydrogels in Drug Delivery: Progress and Challenges”, Polymer, Vol. 49, pp. 1993-2007, 2008.
7. Cui, W., Li, X., Zhu, X., Yu, G., Zhou, S., and Weng, J., “Investigation of Drug Release and Matrix Degradation of Electrospun Poly (DL-lactide) Fibers with Paracetanol Inoculation”, Biomacromolecules, Vol. 7, pp. 1623-1629, 2006.
8. Kowalewski, T., NSKI, S., and Barral, S., “Experiments and Modelling of Electrospinning Process”, Technical Sciences, Vol. 53, pp. 385-394, 2005.
9. Shahidi, F., and Abuzaytoun, R., “Chitin, Chitosan, and Co-Products: Chemistry, Production, Applications, and Health Effects”, Advances in Food and Nutrition Research, Vol. 49, pp. 93-137, 2005.
10. Cipitria, A., Skelton, A., Dargaville, T., Dalton, P., and Hutmacher, D., “Design, Fabrication and Characterization of PCL Electrospun Scaffolds-A Review”, Journal of Materials Chemistry, Vol. 21, pp. 9419-9453, 2011.
11. Winocur, G., Vardy, J., Binns, M. A., Kerr, L., and Tannock, I., “The Effects of the Anti-Cancer Drugs, Methotrexate and 5-Fluorouracil, on Cognitive Function in Mice”, Pharmacology Biochemistry and Behavior, Vol. 85, pp. 66-75, 2006.
12. Zhang, N., Yin, Y., Xu, S. -J., and Chen, W. -S., “5-Fluorouracil: Mechanisms of Resistance and Reversal Strategies”, Molecules, Vol. 13, pp. 1551-1569, 2008.
13. Allen, T. M., and Cullis, P. R., “Drug Delivery Systems: Entering the Mainstream”, Science, Vol. 303, pp. 1818-1822, 2004.
14. Sadrearhami, Z., Morshed, M., and Varshosaz, J., “Production and evaluation of polyblend of agar and polyacrylonitrile Nanofibers for in Vitro Release of Methotrexate in Cancer Therapy”, Fibers and Polymers, Vol. 16, pp. 254-262, 2015.
15. Gupta, K. K., Pal, N., Mishra, P. K., Srivastava, P., Mohanty, S., and Maiti, P., “5‐Florouracil‐Loaded Poly (Lactic Acid)‐Poly (Caprolactone) Hybrid Scaffold: Potential Chemotherapeutic Implant”, Journal of Biomedical Materials Research Part A, Vol. 102, pp. 2600-2612, 2014.
16. Fathi-Azarbayjani, A., and Chan, S. Y., “Single and Multi-Layered Nanofibers for Rapid and Controlled Drug Delivery”, Chemical and Pharmaceutical Bulletin, Vol. 58, pp. 143-146, 2010.
17. Laha, A., Sharma, C. S., and Majumdar, S., “Sustained Drug Release from Multi-Layered Sequentially Crosslinked Electrospun Gelatin Nanofiber Mesh”, Materials Science and Engineering: C, Vol. 76, pp. 782-786, 2017.
18. Okuda, T., Tominaga, K., and Kidoaki, S., “Time-Programmed Dual Release Formulation by Multilayered Drug-Loaded Nanofiber Meshes”, Journal of Controlled Release, Vol. 143, pp. 258-264, 2010.
19. Zeng, J., Yang, L., Liang, Q., Zhang, X., Guan, H., Xu, X., Chen, X., and Jing, X., “Influence of the Drug Compatibility with Polymer Solution on the Release Kinetics of Electrospun Fiber Formulation”, Journal of Controlled Release, Vol. 105, pp. 43-51, 2005.
20. Van der Schueren, L., Steyaert, I., De Schoenmaker, B., and De Clerck, K., “Polycaprolactone/Chitosan Blend Nanofibres Electrospun from an Acetic Acid/Formic Acid Solvent System”, Carbohydrate Polymers, Vol. 88, pp. 1221-1226, 2012.
21. Semnani, D., Naghashzargar, E., Hadjianfar, M., Dehghan Manshadi, F., Mohammadi, S., Karbasi, S., and Effaty, F., “Evaluation of PCL/Chitosan Electrospun Nanofibers for Liver Tissue Engineering”, International Journal of Polymeric Materials and Polymeric Biomaterials, Vol. 66, pp. 149-157, 2017.
22. Semnani, D., Nasari, M., and Fakhrali, A., “PCL Nanofibers Loaded with Beta-Carotene: A Novel Treatment for Eczema”, Polymer Bulletin, Vol. 75, pp. 1-12, 2018.
23. Bi, Y., Cao, X., Liu, M., Meng, X., and Zhai, H., “A Smart Drug Delivery System in Response to Time, pH and Enzyme for Colorectal Cancer Therapy and Its Targeted Release Performance in Vitro”, Materials Letters, Vol. 137, pp. 354-357, 2014.
24. Hadjianfar, M., Semnani, D., and Varshosaz, J., “Polycaprolactone/Chitosan Blend Nanofibers Loaded by 5‐Fluorouracil: An Approach to Anticancer Drug Delivery System”, Polymers for Advanced Technologies, Vol. 29, pp. 2972-2981, 2018.
25. Qian, Y., Zhang, Z., Zheng, L., Song, R., and Zhao, Y., “Fabrication and Characterization of Electrospun Polycaprolactone Blended with Chitosan-Gelatin Complex Nanofibrous Mats”, Journal of Nanomaterials, Vol. 2014, p. 1, 2014.
مواد پیشرفته در مهندسی
دوره 38، شماره 4
بهمن 1398
صفحه 1-17

فایل ها

هم رسانی

ارجاع به این مقاله

آمار

ارتقاء امنیت وب با وف ایرانی