مواد و فناوری‌های پیشرفته

مواد و فناوری‌های پیشرفته

تولید و مشخصه‌یابی هیدروژل حساس به دما و قابل‌تزریق پلارونیک F127 برای کاربرد رهایش هدفمند دارو در درمان سرطان

نوع مقاله : مقاله کامل پژوهشی

نویسندگان
1 کارشناسی ارشد، دانشکده مهندسی ساخت و فناوری‌های صنعتی، واحد نجف‌آباد، دانشگاه آزاد اسلامی، نجف‌آباد، اصفهان، ایران
2 استاد، دانشکده مهندسی ساخت و فناوری‌های صنعتی، واحد نجف‌آباد، دانشگاه آزاد اسلامی، نجف‌آباد، اصفهان، ایران
3 استادیار، گروه مهندسی شیمی، واحد شهرضا، دانشگاه آزاد اسلامی، شهرضا، اصفهان، ایران
چکیده
در این مطالعه، یک هیدروژل قابل‌تزریق از جنس Pluronic F127 حاوی دوکسوروبیسین (DOX) با خواص حساسیت به دما برای دارورسانی در محل و موضعی تهیه شد. هیدروژل به «روش سرد» تهیه شد و تأثیر غلظت هیدروژل بر دمای ژل شدن و ویسکوزیته و تأثیر دما بر میزان رهایش دارو بررسی شد. غلظت‌های گوناگون هیدروژل F127 از نظر ویسکوزیته و سایر ویژگی‌ها و رهایش دوکسوروبیسین در دمای طبیعی بافت بدن (37 درجه‌ی سلسیوس) و در دمای تومور سرطانی (۴3 درجه‌ی سلسیوس) بررسی شد. غلظت بهینه‌ی هیدروژل F127 معادل ۲۰ درصد وزنی‌حجمی انتخاب و خواص رئولوژیکی و رهایش داروی آن بررسی شد. هیدروژل F127 با مادون قرمز تبدیل فوریه (FTIR) و پراش پرتو ایکس (XRD) مشخصه‌یابی شد و با استفاده از میکروسکوپ الکترونی روبشی نشر میدانی با تابش پراکندگی انرژی (FE-SEM/EDS) بررسی شد. نتایج آزمون رهایش دارو حاکی از رهایش موفق دوکسوروبیسین در هر دو دما بود. نتایج نشان می‌دهد که مقدار دوکسوروبیسین آزادشده با افزایش دما حدود ۱۸-۲۰ درصد افزایش می‎یابد که برای درمان تومورهای بدخیم مهم است. نتایج آزمون MTT همچنین نشان می‌دهد که هیدروژل حاوی دارو باعث کاهش زنده ماندن سلول‏های سرطانی می‎شود و تنها 32 درصد از سلول‎ها پس از 72 ساعت در محیط کشت زنده مانده‎اند.
کلیدواژه‌ها

موضوعات


عنوان مقاله English

Preparation and Characterization of an Injectable Thermosensitive Pluronic F127 Hydrogel for Targeted Drug Delivery in Cancer Treatment

نویسندگان English

Mahtab Farzaneh 1
Sayed Ali Hassanzadeh-Tabrizi 2
Nader Mokhtarian 3
1 Master of Biomedical Engineering Graduate, Institute of Manufacturing Engineering and Industrial Technologies, Na.C, Islamic Azad University, Najafabad, Isfahan, Iran.
2 Professor, Institute of Manufacturing Engineering and Industrial Technologies, Na.C, Islamic Azad University, Najafabad, Isfahan, Iran.
3 Assistant Professor, Department of Chemical Engineering, Shahreza Branch, Islamic Azad University, Shahreza, Isfahan, Iran.
چکیده English

In this study, an injectable hydrogel made from Pluronic F127 containing Doxorubicin (DOX), with thermosensitive properties for localized drug delivery, was prepared using the cold method. The effects of hydrogel concentration on gelation temperature and viscosity, as well as the effect of temperature on drug release rate, were investigated. Different concentrations of F127 hydrogel were evaluated for viscosity and other characteristics, and Doxorubicin release was studied at body temperature (37℃) and tumor temperature (43℃). The optimal concentration of F127 hydrogel was selected as 20% w/v, and its rheological and drug release properties were examined. The hydrogel was characterized using Fourier Transform Infrared (FTIR) and X-Ray Diffraction (XRD), and examined through Field Emission Scanning Electron Microscopy with Electrophoretic Light Scattering (FE-SEM/EDS). The drug release assay results indicated successful Doxorubicin release at both temperatures. The release increased by 18-20% with temperature rise, which is significant for malignant tumor treatment. The MTT assay results showed that the drug-containing hydrogel reduced cancer cell viability, with only 32% of the cells surviving after 72 hours in culture.

کلیدواژه‌ها English

Hydrogel
Doxorubicin
F127
Cancer
Temperature Sensitive
  1. Abbas, Z., & Rehman, S. (2018). An overview of cancer treatment modalities. Neoplasm, 1, 139-157. http://dx.doi.org/10.5772/intechopen.76558
  2. Abedini, F., Ebrahimi, M., Roozbehani, A. H., Domb, A. J., & Hosseinkhani, H. (2018). Overview on natural hydrophilic polysaccharide polymers in drug delivery. Polymers for Advanced Technologies,. 29(10), 2564-2573. https://doi.org/10.1002/pat.4375
  3. Ali Ibrahim, E. S., Ismail, S., Fetih, G., Shaaban, O., Hassanein, K., & Abdellah, N. H. (2012). Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application. Acta pharmaceutica, 62(1), 59-70. https://doi.org/10.2478/v10007-012-0009-y
  4. Bahuguna, A., Khan, I., Bajpai, V. K., & Kang, S. C. (2017). MTT assay to evaluate the cytotoxic potential of a drug. Bangladesh Journal of Pharmacology, 12(2), 115-118. http://dx.doi.org/10.3329/bjp.v12i2.30892
  5. Çetingül, M. P., & Herman, C. (2011). Quantification of the thermal signature of a melanoma lesion. International Journal of Thermal Sciences, 50(4), 421-431 http://dx.doi.org/10.1016/j.ijthermalsci.2010.10.019
  6. Chatterjee, S., Hui, P. C. L., Kan, C. W., & Wang, W. (2019). Dual-responsive (pH/temperature) Pluronic F-127 hydrogel drug delivery system for textile-based transdermal therapy. Scientific reports, 9(1), 11658. https://doi.org/10.1038/s41598-019-48254-6
  7. Chen, W., Deng, W., & Goldys, E. M. (2021). Recent Developments of Light: Triggered Liposome Nanosystems for Cancer Treatments. Functional Lipid Nanosystems in Cancer, 485-511. https://doi.org/10.1201/9781003056997
  8. Davenport, E. L., Morgan, G. J., & Davies, F. E. (2008). Untangling the unfolded protein response. Cell cycle, 7(7), 865-869. https://doi.org/10.4161/cc.7.7.5615
  9. Ebadi, T., Najafpour, G. D., Kazemi, S., Hosseini, S. M. (2025). Development and In-vitro Evaluation of a Natural Polysaccharide Hydrogel for Curcumin Delivery. International Journal of Engineering, 38(5), 976-985. https://doi.org/10.5829/ije.2025.38.05b.02
  10. Fan, R., Cheng, Y., Wang, R., Zhang, T., Zhang, H., Li, J., ... & Zheng, A. (2022). Thermosensitive hydrogels and advances in their application in disease therapy. Polymers, 14(12), 2379. https://doi.org/10.3390/polym14122379
  11. García-Couce, J., Tomás, M., Fuentes, G., Que, I., Almirall, A., & Cruz, L. J. (2022). Chitosan/Pluronic F127 thermosensitive hydrogel as an injectable dexamethasone delivery carrier. Gels, 8(1), 44. https://doi.org/10.3390/gels8010044
  12. Gatenby, R. A., & Gillies, R. J. (2008). A microenvironmental model of carcinogenesis. Nature Reviews Cancer, 8(1), 56-61. https://doi.org/10.1038/nrc2255
  13. Hosseinkhani, H. (2019). Nanomaterials in advanced medicine. ISBN: 978-3-527-81893-8. https://www.wiley.com/en-us/Nanomaterials+in+Advanced+Medicine
  14. Hosseinkhani, H. (2022). Biomedical Engineering: Materials, Technology, and Applications. John Wiley & Sons. http://dx.doi.org/10.1002/9783527826674
  15. Kazemi, M., Chogan., F., Rezayan., A. H., Mehdinavaz Aghdam., R., & Ahmadi Tafti, S. H. (2022). Injectable Thermosensitive Hydrogel (Chitosan/Gelatin/β-Glycerol Phosphate) Reinforced with Polyaniline/Carboxylated Carbon Nanotube/Gelatin Containing Stem Cells for Cardiac Tissue Engineering. Journal of Advanced Materials and Technologies (JAMT), 11(2), 71-87. [In Persian]. https://doi.org/10.30501/jamt.2023.311513.1199
  16. Knapp, J. P., Knapp, J. P., Kakish, J. E., Bridle, B. W., & Speicher, D. J. (2022). Tumor temperature: friend or foe of virus-based cancer immunotherapy. Biomedicines, 10(8), 2024. https://doi.org/10.3390/biomedicines10082024
  17. Moniri Javadhesari, S., Jabraili, M., Koohi, M. (2022). A Review on the Application of Nanoparticles for Targeted Gene Delivery. Advanced Ceramics Progress, 8(1), 44-55. https://doi.org/10.30501/acp.2022.345741.1091
  18. Moore, T., Croy, S., Mallapragada, S., & Pandit, N. (2000). Experimental investigation and mathematical modeling of Pluronic® F127 gel dissolution: drug release in stirred systems. Journal of Controlled Release, 67(2-3), 191-202. https://doi.org/10.1016/s0168-3659(00)00215-7
  19. Nie, S., Hsiao, W. W., Pan, W., & Yang, Z. (2011). Thermoreversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies. International journal of nanomedicine, 151-166. https://doi.org/10.2147/IJN.S15057
  20. Norouzi, M., Nazari, B., & Miller, D. W. (2016). Injectable hydrogel-based drug delivery systems for local cancer therapy. Drug discovery today, 21(11), 1835-1849. https://doi.org/10.1016/j.drudis.2016.07.006
  21. Phutane, P., Telange, D., Agrawal, S., Gunde, M., Kotkar, K., & Pethe, A. (2023). Biofunctionalization and applications of polymeric nanofibers in tissue engineering and regenerative medicine. Polymers, 15(5), 1202. https://doi.org/10.3390/polym15051202
  22. Pouso, M. R., Melo, B. L., Gonçalves, J. J., Mendonça, A. G., Correia, I. J., & de Melo-Diogo, D. (2024). Development of dual-crosslinked Pluronic F127/Chitosan injectable hydrogels incorporating graphene nanosystems for breast cancer photothermal therapy and antibacterial applications. European Journal of Pharmaceutics and Biopharmaceutics, 203, 114476. https://doi.org/10.1016/j.ejpb.2024.114476
  23. Romić, M. D., Klarić, M. Š., Lovrić, J., Pepić, I., Cetina-Čižmek, B., Filipović-Grčić, J., & Hafner, A. (2016). Melatonin-loaded chitosan/Pluronic® F127 microspheres as in situ forming hydrogel: An innovative antimicrobial wound dressing. European Journal of Pharmaceutics and Biopharmaceutics, 107, 67-79. https://doi.org/10.1016/j.ejpb.2016.06.013
  24. Saini, A., Kumar, M., Bhatt, S., Saini, V., & Malik, A. (2020). Cancer causes and treatments. J. Pharm. Sci. Res, 11(7), 3121-3134. https://doi.org/ 10.13040/IJPSR.0975-8232.11(7).3109-22
  25. Salama, A. H. (2021). PLURONIC F127 and ITS applications. Pharmacologyonline, 2, 1393-403. ISSN: 1827-8620. https://pharmacologyonline.silae.it/files/archives/2021/vol2/PhOL_2021_2_A153_Salama.pdf
  26. Schmolka, I. R. (1972). Artificial skin I. Preparation and properties of pluronic F‐127 gels for treatment of burns. Journal of biomedical materials research, 6(6), 571-582. https://doi.org/10.1002/jbm.820060609
  27. Singla, P., Garg, S., McClements, J., Jamieson, O., Peeters, M., & Mahajan, R. K. (2022). Advances in the therapeutic delivery and applications of functionalized Pluronics: A critical review. Advances in Colloid and Interface Science, 299, 102563 https://doi.org/10.1016/j.cis.2021.102563
  28. Sung, Y. K., & Kim, S. W. (2020). Recent advances in polymeric drug delivery systems. Biomaterials Research, 24(1), 12. https://doi.org/10.1186/s40824-020-00190-7
  29. Tanga, S., Aucamp, M., & Ramburrun, P. (2023). Design and characterisation of a Pluronic-F127-based injectable thermoresponsive intratumoural hydrogel. SA Pharmaceutical Journal, 90(1), 41-44. https://research-nexus.net/paper/78841
  30. Ünal, S., Çelik Tekeli, M., Doğan, O., & Aktaş, Y. (2023). Thermosensitive pluronic® F127-based in situ gel formulation containing nanoparticles for the sustained delivery of paclitaxel. http://dx.doi.org/10.5455/medscience.2022.11.252
  31. Vaupel, P., & Mayer, A. (2007). Hypoxia in cancer: significance and impact on clinical outcome. Cancer and Metastasis Reviews, 26, 225-239. https://doi.org/10.1007/s10555-007-9055-1
  32. Wen, Q., Zhang, Y., Luo, J., Xiong, K., Lu, Y., Wu, Z., ... & Fu, S. (2020). Therapeutic efficacy of thermosensitive Pluronic hydrogel for codelivery of resveratrol microspheres and cisplatin in the treatment of liver cancer ascites. International Journal of Pharmaceutics, 582, 119334. https://doi.org/10.1016/j.ijpharm.2020.119334
دوره 14، شماره 1
بهار 1404
صفحه 28-42

  • تاریخ دریافت 17 بهمن 1403
  • تاریخ بازنگری 22 اسفند 1403
  • تاریخ پذیرش 05 خرداد 1404