بررسی رهایش نانوحامل‌های دارویی پایه کیتوسان در درمان تومورهای سرطانی
محورهای موضوعی : سامانه های پلیمری تحریک پذیرمحمدحسین کرمی 1 , مجید عبدوس 2 , ماندانا کرمی 3
1 - دانشکده شیمی، دانشگاه صنعتی امیر کبیر (پلی تکنیک تهران)
2 - دانشکده شیمی، دانشگاه صنعتی امیرکبیر ، تهران، صندوق پستی: 4413- 15875
3 - پژوهشگاه پلیمر و پتروشیمی، تهران، ایران، صندوق پستی: 112- 14975
کلید واژه: نانوحامل, کیتوسان, سرطان, تومور, رهایش دارو,
چکیده مقاله :
سامانه‌های هدفمند رهایش دارو منجر به کاهش عوارض جانبی در بدن انسان می‌شوند و به‌دلیل افزایش نفوذپذیری، امکان تجمع بهتر داروها در محل تومور سرطانی را فراهم می‌کنند. سرعت رهاسازی آهسته برای کاربرد رهایش دارو مناسب است، زیرا میزان آسیب به سلول‌های طبیعی را کاهش می‌دهد و منجر به کاهش عوارض جانبی می‌شود. پیوند هیدروژنی در محیط بافت سالم، باعث افزایش پایداری می‌شود و همچنین ساخت نانوحامل دارویی به روش امولسیونی دوگانه باعث رهایش داروها به‌صورت آهسته می‌شود. استفاده از نانوذرات به‌عنوان حامل دارو نیز به‌دلیل قابلیت حمل دارو به قسمت‌های مختلف بدن در زمان مناسب، بسیار مهم است. استفاده از سامانه‌های دارورسانی بر پایه نانوذرات بارگذاری شده با عوامل ضدسرطان، روشی موثر برای هدف‌گذاری سلول‌های سرطانی است. این سامانه‌ها با قابلیت نفوذ بهتر در داخل سلول‌ها، دارو را به صورت هدفمند در سلول‌ها ترکیب می‌کنند. همچنین، به‌دلیل افزایش نفوذپذیری (EPR)، امکان تجمع بهتر داروها در محل تومور فراهم می‌شود. در سامانه‌های دارورسانی، افزایش رهایش در محیط سرطانی نسبت به سامانه‌های فیزیولوژیکی به‌عنوان مزیت برای کاهش سمیت بر روی بافت سالم در نظر گرفته می‌شود. در این پژوهش برای اولین بار، پروفایل رهایش نانوحامل‌های دارویی حاوی داروهای ضدسرطان بررسی شده است
Chitosan has been widely used as a natural biopolymer. The modification of chitosan for various applications can be easily achieved due to the abundant active groups (NH2 and OH) in the main chain. Controlled drug release makes the drug release rate predictable and repeatable for prolonged release drugs. Drug delivery systems prepared from nanoparticles show several advantages, including improved efficiency and reduced toxicity. Using drug delivery systems based on nanoparticles loaded with anti-cancer agents is an effective method for targeting cancer cells. These systems, with the ability to penetrate better inside the cells, combine the drug in a targeted way in the cells. Also, due to the enhanced permeability and retention (EPR), the possibility of better accumulation of drugs in the tumor site is provided. In most researches, the suitable particle size for the targeted release of drug nanocarriers has been reported to be less than 300 or 200 nm. This amount is suitable for the application of drug release for diffusion among tissues and causes the effect of increasing permeability. In this study, for the first time, it examines and analyzes the particle size and zeta potential (surface charge) of chitosan-based nanocarriers through dynamic light scattering and electron microscope tests in improving the release of the antitumor drug, 5-fluorouracil.
1. Tang J.D., Mura C., Lampe K.J., Stimuli-Responsive,
Pentapeptide, Nanofiber Hydrogel for Tissue Engineering, Journal of the American Chemical Society, 141, 4886-99, 2019.
2. Khorasani MT., Joorabloo A., Adeli H., Mansoori-Moghadam Z, Moghaddam A., Design and Optimization of Process Parameters of Polyvinyl (alcohol)/ Chitosan/Nano Zinc Oxide Hydrogels as Wound Healing Materials, Carbohydrate Polymers, 207, 542-54, 2019.
3. Ali A., Ahmed S., A Review on Chitosan and its Nanocomposites in Drug Delivery, International Journal of Biology Macromolecule, 109, 273-86, 2018.
4. Haraguchi K., Nanocomposite Hydrogels, Current Opinion Solid State Material Science, 11:47–54, 2017.
5. Satarkar NS., Biswal D., Hilt JZ., Hydrogel Nanocomposites: A Review of Applications as Remote Controlled Biomaterials, Soft Matter, 6, 2364-71, 2010.
6. Gooneh-Farahani S., Naimi-Jamal MR., Naghib SM.,
Stimuliresponsive Grapheme Incorporated Multifunctional Chitosan for Drug Delivery Applications: A Review, Expert Opinion Drug Delivery, 16, 79–99, 2019.
7. Kaur R., Kaur S., Roles of Polymers in Drug Delivery,
Journal of Drug Delivery, 4, 32, 2014.
8. LaftahWA., Hashim S., Ibrahim AN., Polymer Hydrogels: A Review, Polymer-Plastics Technology and Materials, 50, 1475–86,2011.
9. Zhao F., Yao D., Guo R., Deng L., Dong A., Zhang J.,
Composites of Polymer Hydrogels and Nanoparticulate Systems for Biomedical and Pharmaceutical Applications, Nanomaterial, 5, 2054-130, 2015.
10. Sannino A., Demitri C., Madaghiele M., Biodegradable Cellulosebased Hydrogels: Design and Applications. Material, 2, 353- 73, 2019.
11. Ma J., Li X., Bao Y., Advances in Cellulose-Based Superabsorbent Hydrogels, RSC Advanves, 5, 59745-57, 2015.
12. Gholamali I., Stimuli-Responsive Polysaccharide Hydrogels for Biomedical Applications: A Review, Regenerative
Engineering and Translational Medicine, 7, 1- 24, 2019.
13. HeM., Zhao Y., Duan J.,Wang Z., ChenY., Zhang L., Fast Contact of Solid-Liquid Interface Created High Strength Multi-layered Cellulose Hydrogels with Controllable Size, ACS Applies Material Interfaces, 6,1872–8, 2014.
14. Qiu X., Hu S.,Smart., Materials Based on Cellulose: A
Review of the Preparations, Properties and Applications, Material, 6,738- 81, 2013.
15. Barkhordari S., Yadollahi M., Carboxymethyl Cellulose Capsulated Layered Double Hydroxides/Drug Nanohybrids for Cephalexin Oral Delivery, Applied Clay Science,121, 77-85, 2016.
16. Yadollahi M., Gholamali I., Namazi H., Aghazadeh M., Synthesis and Characterization of Antibacterial Carboxymethyl Cellulose/ZnO Nanocomposite Hydrogels, International Journal of Biological Macromolecules, 74, 136–41, 2015.
17. Yadollahi M., Namazi H., Aghazadeh M., Antibacterial Carboxymethyl Cellulose/Ag Nanocomposite Hydrogels Crosslinked with Layered Double Hydroxides, International Journal of Biological Macromolecules, 79, 269-77, 2015.
18.Yadollahi M., Gholamali I., Namazi H., Aghazadeh M., Synthesis and Characterization of Antibacterial Carboxymethylcellulose/CuO Bio-Nanocomposite Hydrogels, International Journal of Biological Macromolecules, 73, 109-14, 2014.
19. Gholamali I., Facile Preparation of Carboxymethyl Cellulose/Cu Bio-Nanocomposite Hydrogels for Controlled Release of Ibuprofen, Regenerative Engineering and Translational Medicine, 6, 115, 24, 2020.
20. Foroutan R., Ahmadlouydarab M., Ramavandi B.,
Mohammadi R.,Studying the Physicochemical Characteristics and Metals Adsorptive Behavior of CMC-g-HAp/Fe3O4
Nanobiocomposite., The Journal of Environmental Chemical Engineering, 6, 6049, 58, 2018.
21. Shen J., Song Z., Qian X., Yang F., Carboxymethyl
Cellulose, Journal of Non-Crystalline Solids, 511, 201–11, 2019.
22. Che Nan NF., Zainuddin N., Ahmad M., Preparation and Swelling Study of CMC Hydrogel as Potential Superabsorbent, Journal of Science & Technology, 27, 489-98, 2019.
23. Behzadi Nia S., Pooresmaeil M., Namazi H., CarboxymethylCellulose/ Layered Double Hydroxides Bio-Nanocomposite Hydrogel:a Controlled Amoxicillin Nanocarrier for Colonic
Bacterial Infections Treatment, International Journal of
Biological Macromolecules, 155, 1401–9, 2020.
24. Youssef AM., El-Sayed SM., Bionanocomposites Materials
for Food Packaging Applications: Concepts and Future
Outlook, Carbohydrate Polymers, 193, 19-27, 2018.
25. Rakhshaei R., Namazi H. A., Potential Bioactive Wound Dressing Based on Carboxymethyl Cellulose/ZnO Impregnated
MCM-41 Nanocomposite Hydrogel, Materials Science and Engineering: C, 73, 456–64,2017.
26. Javanbakht S., Shaabani A., Carboxymethyl Cellulose-
Based Oral Delivery Systems, International Journal of Biological Macromolecules, 133, 9–21, 2019.
27.Farhoudian S., Yadollahi M., Namazi H., Facile Synthesis of Antibacterial Chitosan/CuO Bio-Nanocompositehydrogel Beads, International Journal of Biological Macromolecules, 82, 837–843, 2016.
28. Upadhyaya L., Singh J., Agarwal V., Tewari RP., The
Implications of Recent Advances in Carboxymethyl Chitosan Based Targeted Drug Delivery and Tissue Engineering Applications, Journal of Control Release, 186, 54–87, 2014.
29. Yamada M., Foote M., Prow TW., Therapeutic Gold, Silver, and Platinum Nanoparticles, Wires Nanomed Nanobiotechnology,
7, 428–445, 2015.
30. Khorasani MT., Joorabloo A., Moghaddam A., Shamsi H., Mansoori MZ., Incorporation of ZnO Nanoparticles into Heparinised Polyvinyl Alcohol/Chitosan Hydrogels for Wound Dressing Application, International Journal of Biological Macromolecules, 114, 1203–15, 2018.
31. Chen R., Chen Q., Huo D., Ding Y., HuY., Jiang X., In situ Formation of Chitosan-Gold Hybrid Hydrogel and Its Application For Drug Delivery, Colloid Surface B: Biointerfac, 97, 132–1377, 2012.
32. Li T., Zhang M., Wang J., Wang T., Yao Y., Zhang X.,
Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy, Journal of the American Association of Pharmaceutical Scientists, 18, 146–55, 2016.
33. Zhang Z., He Z., Liang R., Ma Y., Huang W., Jiang R., Fabrication of a Micellar Supramolecular Hydrogel for Ocular Drug Delivery, Biomacromolecules, 17, 798, 807, 2016.
34. Satarkar NS., Biswal D., Hilt JZ., Hydrogel Nanocomposites: A Review of Applications as Remote Controlled Biomaterials, Soft Matte, 6, 2364–71, 2010.
35. Sun X., Liu C., Omer AM., Lu W., Zhang S., Jiang X., pH Sensitive ZnO/Carboxymethyl Cellulose/Chitosan Bionanocomposite Beads for Colon-specific Release of 5-fluorouracil,
International Journal of Biological Macromolecules, 128, 468–79, 2019.
36. Gholamali I., Hosseini SN., Alipour E., Yadollahi M., Preparation and Characterization of Oxidized Starch/CuO nanocomposite Hydrogels Applicable in a Drug Delivery
System. Starch/Stärke, 71, 1800118, 2019.
37. Karami M. H., KalaeeM. R.,Investigation of Curing Kinetics Modeling of Epoxy Nanocomposites in the Presence of Nano Graphene Oxide: A Review Study, Iranian Chemical
Engineering Journal, 21(124), 71-83, 2022.
38. Karami M. H., Kalaee M.R ., Khajavi R., Moradi O., Zaarei D., Effect of Nano Diamond on Thermal Behavior and Thermal Stability of Epoxy Resin, Nano World, 18, 11-19, 2022.
39.Lombardo D., Kiselev MA., Caccamo MT., Smart Nanoparticles for Drug Delivery Application: Development of Versatile Nanocarrier Platforms in Biotechnology and Nanomedicine, International Journal of Nanomedicin, 1-29, 2019.
40. Karami M.H., Abdouss M., Kalaee M.R., MoradiO., Investigating the Antibacterial Properties of Chitosan Nanocomposites Containing Metal Nanoparticles for Using in Wound Healings: A Review Study, Basparesh, In Press, 2023.
41. Qiu X., Hu S., Smart Materials Based on Cllulose: A Review of the Preparations, Properties, and Applications, Materials,
6, 738– 81, 2013.
42. Karami M.H., Kalaee M.R., Khajavi R., Moradi O., Zaarei D., Thermal Degradation Kinetics of Epoxy Resin Modified with Elastomeric Nanoparticles, Advanced Composite and Hybrid Materials, 5, 390-401, 2022.
43. Karami M.H., Kalaee M.R., Mazinani S., Shakiba M.,
Shafiei N.S., Abdouss M., Beig Mohammadi A.,Zhao W., Koosha
M., Song Z.,Li T., Curing Kinetics Modeling of Epoxy
Modified by Fully Vulcanized Elastomer Nanoparticles Using Rheometry Method, Molecules, 27, 2870, 2022.
44. Patra J.K., Das G., Fraceto L.F., Campos E.V., Del Pilar Rodriguez- Torres M., Acosta-Torres LS., Diaz-Torres L.A., Grillo R., Swamy M.K., Sharma S., Habtemariam S., Nano Based Drug Delivery Systems: Recent Developments and Future Prospects, J. Nanobiotechnology, 16, 1-33, 2018.
45. Xie X., Zhang Y., Li F., Lv T., Li Z., Chen H., Jia L., Gao Y., Challenges and Opportunities from Basic Cancer Biology forNanomedicine for Targeted Drug Delivery., Current Cancer Drug Targets, 19, 257-276, 2019.
46. Pattni B.S., Chupin V.V., Torchilin V.P., New Developments in Liposomal Drug Delivery., Chemical Reviews., 115, 10938–10966, 2015.
47. Abu-Thabit N.Y., Makhlouf A.S., Historical Development of Drug Delivery Systems: From Conventional Macroscaleto Controlled, Targeted, and Responsive Nanoscale Systems., Woodhead Publishing, Holland, 3-41, 2018.
48. Weinberg B.D., Blanco E., Gao J., Polymer Implants for Intratumoral Drug Delivery and Cancer Therapy, Journal ofPharmaceutical Sciences, 97, 1681–1702, 2008.
49. Jia X., He J., Shen L., Chen J., Wei Z., Qin X., Niu D., Li Y., Shi J., Gradient Redox-Responsive and Two-Stage Rocket- Mimetic Drug Delivery System for Improved Tumor Accumulation and Safe Chemotherapy, Nano Letter., 19, 8690–8700, 2019.
50. Yin Q., Shen J., Zhang Z., Yu H., Li Y., Reversal of Multidrug Resistance by Stimuli-Responsive Drug Delivery
Systems for Therapy of Tumor, Advanced Drug Delivery
Reviews., 65, 1699– 1715, 2013.
51. Karami M.H., Pourmadadi M., Abdouss M., Kalaee M.R., Moradi O., Rahdar A., Díez-Pascual A.M., Novel Chitosan/ γ-alumina/carbon Quantum Dot Hydrogel Nanocarrier for Targeted Drug Delivery, International Journal of Biological
Macromolecules., 251, 126280(1-13), 2023.