ساخت حامل نانولیفی پلی‌لاکتیک اسید حاوی داروی دگزامتازون

نویسندگان

گروه بیومتریال، دانشکده مهندسی پزشکی، دانشگاه صنعتی امیرکبیر، تهران، ایران

چکیده

دگزامتازون به‌عنوان داروی ضدالتهاب سال‌هاست به شکل‌های مختلف مصرف می‌شود و هنوز یکی از امن‌ترین داروهای گلوکوکورتیکوئیدی برای درمان بیماری‌های مختلف است. به‌سبب وجود طیف گسترده از اثرات جانبی، پیدا کردن یک سامانه رهایشی مناسب برای افزایش اثربخشی و کاهش میزان دوز مصرفی این دارو ضروری است. الکتروریسی یکی از روش‌های ساخت الیاف پلیمری است که به‌دلیل توانایی بارگیری داروها و مواد بیولوژیکی مختلف و کنترل رهایش آنها به‌طور گسترده برای ساخت حامل‌های دارویی مورد استفاده قرار می‌گیرد. در این پژوهش الیاف الکتروریسی شده پلی‌لاکتیک ‌اسید فاقد و حاوی دگزامتازون تهیه شد. برای بررسی تأثیر غلظت پلیمر بر مورفولوژی، خواص مکانیکی الیاف و نمودار رهایش دارو، سه غلظت 10، 14 و 18 درصد وزنی/حجمی پلیمر تهیه شد. به نمونه‌ها پنج درصد وزنی/حجمی دگزامتازون اضافه شد. تصاویر میکروسکوپی الکترونی روبشی برای به‌دست آوردن میانگین قطر الیاف و میانگین مساحت حفره‌ها در هر نمونه بررسی شد. در نمونه‌های فاقد دارو میانگین قطر الیاف حاوی 10 تا 18 درصد وزنی، 63/21 درصد افزایش یافت. در نمونه‌های حاوی دارو میانگین قطر الیاف از نمونه 10 تا 18 درصد، 51/19 درصد افزایش یافت. خواص مکانیکی پلیمر مورد بررسی قرار گرفت. مدول الاستیک از نمونه 10 درصد تا نمونه 18 درصد، 81/34 درصد افزایش یافت. افزایش 68/021 درصد استحکام نهایی از نمونه 18 درصد نسبت به نمونه 10 درصد دیده شد. رهایش دارو برای نمونه‌های الکتروریسی تا هفت روز انجام شد. در نمونه‌های 10 و 14 درصد رهایش خطی مشاهده شد. مدل رهایش دارو از نمونه‌ها درجه صفر بود که با توجه به اینکه این مدل رهایش دارو در کاربردهای مختلف دگزامتازون حائز اهمیت است، سامانه‌های طراحی شده می‌توانند برای کاربردهای مختلف دگزامتازون مفید باشند. بیشترین سرعت رهایش دارو مربوط به نمونه 14 درصد بود (0/044 بر ساعت).

کلیدواژه‌ها


عنوان مقاله [English]

Fabrication of Poly (Lactic Acid) Nanofiber Carrier Loaded with Dexamethasone Drug

نویسندگان [English]

  • S. Torabi
  • S. Khorshidi
  • A. Karkhaneh
Biomaterial Group, Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran, Iran.
چکیده [English]

For many years, dexamethasone has been used as an anti-inflammatory drug and is still one of the safest glucocorticoids for treating various diseases. Due to the wide range of the side effects of this drug, it is essential to find a suitable delivering system for reduction in dosage with increased effectiveness. Electrospinning is one of the fiber fabrication methods which is widely used to develop drug carriers due to its ability to load various drugs and biological components and control their release. In this research, neat poly (lactic acid) electrospun fibers and dexamethasone loaded fibers were prepared. To evaluate the effect of polymer concentration on morphology, mechanical properties and drug release profile of the resulting fibers, three polymer concentrations of 10%, 14% and 18% w/v were processed. Thereafter, 5% w/v dexamethasone was added to solutions. The scanning electron microscopy images were investigated to obtain the average diameter of fibers and the average area of pores in each sample. In neat samples, by moving from 10% to 18% composition, the average diameter of the fibers increased by 63.21%. However, in drug loaded samples this increased by 51/19%. After evaluating mechanical properties, an increase of 81/34% in Elastic modulus by moving from 10% to 18% composition was observed. Moreover, the ultimate strength increased by 68/021% when increasing the polymer concentration from 10 to 18%. Drug release from the electrospun samples was continued up to 7 days. Linear release was observed in 10% and 14% compositions. The drug release pattern of these samples was of zero order. Considering the importance of zero order release in different applications of dexamethasone, these delivering systems could be useful. The maximum drug release rate belonged to 14% composition (0.044 1/h).

کلیدواژه‌ها [English]

  • Drug delivery
  • Dexamethasone
  • Poly (lactic acid)
  • electrospinning
  • Neat fibers and drug loaded fibers
  • mechanical properties
1. Barnes, P. J., “Glucocorticoids”, Chemical Immunology and Allergy, Vol. 100, pp. 311-316, 2014.
2. Jain, S., and Datta, M., “Oral Extended Release of Dexamethasone: Montmorillonite-PLGA Nanocomposites as a Delivery Vehicle”, Applied Clay Science, Vol. 104. pp. 182-188, 2015.
3. Urbańska, J., Karewicz, A., and Nowakowska, M., “Polymeric Delivery Systems for Dexamethasone”, Life Sciences., Vol. 96, No. 1-2, pp. 1-6, 2014.
4. Yuasa, S. S., Yamada, M. T., Taniyama, T., Masaoka, T., Xuetao, W., Yoshii, T., Horie, M., Yasuda, H., Uemura, T., and Okawa, A, “Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle- Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2”, Journal of Applied Polymer Science, Vol. 10, No. 2, pp. 1-23, 2012.
5. Huebner, K. D., Shrive, N. G., and Frank, C. B., “Dexamethasone Inhibits Inflammation and Cartilage Damage in a New Model of Post-Traumatic Osteoarthritis,” Journal of Orthopaedic Research, Vol. 32, No. 4, pp. 566-572, 2014.
6. Roach, B., Kelmendi-Doko, A., Balutis, E., Marra, K., Ateshian, G., and Hung, C., “Dexamethasone Release from within Engineered Cartilage as a Chondroprotective Strategy Against Interleukin-α”, Tissue Engineering, pp. 621-632, 2016.
7. Oakley, R. H., and Cidlowski, J. A., “Glucocorticoid Signaling in the Heart: A Cardiomyocyte Perspective”, The Journal of Steroid Biochemistry and Molecular Biology, Vol. 153, pp. 27-34, 2015.
8. Kostaras, X., Cusano, F., Kline, G. A., Roa, W., and Easaw, J., “Use of Dexamethasone in Patients with High-Grade Glioma: A Clinical Practice Guideline”, Current Oncology, Vol. 21, No. 3, pp. 493-503, 2014.
9. Atie, M., Khoma, O., Dunn, G., and Falk, G. L., “Gastrointestinal Tract Obstruction Secondary to Post-Operative Oedema: Does Dexamethasone Administration Help?”, Journal of Surgical Case Reports, Vol. 2016, No. 8, p. rjw139, 2016.
10. Gozali, P., Boonsiriseth, K., Kiattavornchareon, S., Khanijou, M., and Wongsirichat, N., “Decreased Post-Operative Pain Using a Sublingual Injection of Dexamethasone (8 mg) in Lower Third Molar Surgery”, Journal of Dental Anesthesia and Pain Medicine, Vol. 17, No. 1, pp. 47-53, 2017.
11. McCall, A. A., Leary Swan, E. E., Borenstein, J. T., Sewell, W. F., , Kujawa, Sh. G., and McKenna, M. J., “Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge”, NIH Public Access, Vol. 114, No. 25, pp. 8291-8300, 2011.
12. Scheper, V., Hessler, R., and Hütten, M., “Local Inner Ear Application of Dexamethasone in Cochlear Implant Models is Safe for Auditory Neurons and Increases the Neuroprotective Effect of Chronic Electrical Stimulation”, PLoS One, Vol. 12, No. 8, pp. 1-22, 2017.
13. Mohabatpour, F., Karkhaneh, A., and Sharifi, A. M., “A hydrogel/Fiber Composite Scaffold for Chondrocyte Encapsulation in Cartilage Tissue Regeneration”, RSC Advances, Vol. 6, No. 86, pp. 83135-83145, 2016.
14. Sun, B., Long, Y. Z., Zhang, H. D., Li, M. M., Duvail, J. L., Jiang, X. Y., and Yin, H. L., “Advances in Three-Dimensional Nanofibrous Macrostructures via Electrospinning”, Progress in Polymer Science, Vol. 39, No. 5, pp. 862-890, 2014.
15. Nathaniel, N., and Vacanti, M., “Investigation of Electrospun Fibrous Scaffolds, Locally Delivered Anti-Inflammatory Drugs, and Neural Stem Cells for Promoting nerve Regeneration” Massachusetts Institute of Technology, pp. 79-82, 2010.
16. Khoo, W., and Koh, C. T., “A Rreview of Eelectrospinning Process and Microstructure Morphology Control”, ARPN Journal of Engineering and Applied Sciences, Vol. 11, No. 12, pp. 7774-7781, 2016.
17. Agarwal, S., Wendorff, J. H., and Greiner, A., “Use of Electrospinning Technique for Biomedical Applications”, Polymer (Guildf) Journal, Vol. 49, No. 26, pp. 5603-5621, 2008.
18. Tang, G. W., Yang, Y. F., Sun, A. P., Song, T. T., Zhao, Y. H., Yuan, X. B., Yuan, X. Y., Fan, Y. B., and Wang, M., “Controlled Release of Dexamethasone from Porous PLGA Scaffolds under Cyclic Loading”, Science China Chemistry, Vol. 53, No. 3, pp. 594-598, 2010.
19. Pisani, A. S., Dorati, R., Chiesa, E., Modena, T., Bruni, G., Genta, I., and Contia, B., “Electrospun Nano Bers for Localized Delivery of Dexamethasone: Preliminary Investigation on Formulation Parameters”, Controlled Release Society, pp. 1-6, 2018.
20. Puppi, D., Zhang, X., Yang, L., Chiellini, F., Sun, X., Chiellini, E., “Nano/Microfibrous Polymeric Constructs Loaded with Bioactive Agents and Designed for Tissue Eengineering Aapplications: A Review”, Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 102, No. 7, pp. 1562-1579, 2014.
21. Aavani, F., Khorshidi, S., and Karkhaneh, A., “A Concise Review on Drug-Loaded Electrospun Nanofibres as Promising Wound Ddressings”, Journal of Medical Engineering & Technology, pp. 1-10, 2019.
22. Sill, T. J., and von Recum, H. A., “Electrospinning: Applications in Drug Delivery and Tissue Engineering”, Biomaterials, Vol. 29, No. 13, pp. 1989-2006, 2008.
23. Casper, C. L., Yang, W., Farach-Carson, M. C., and Rabolt, J. F., “Coating Electrospun Collagen and Gelatin Fibers with Perlecan Domain I for Increased Growth Factor Binding”, Biomacromolecules, Vol. 8, No. 4, pp. 1116-1123, 2007.
24. Ansari, S., Karkhaneh, A., Bonakdar, S., and Haghighipour, N., “Simultaneous Effects of Hydrostatic Pressure and Dexamethasone Release from Electrospun Fibers on Inflammation-Induced Chondrocytes”, European Polymer Journal, Vol. 118, pp. 244-253, 2019.
25. Chen, S. C., Huang, X. B., Cai, X. M., Lu, J., Yuan, J., and Shen, J., “The Influence of Fiber Diameter of Electrospun Poly(Lactic Acid) on Drug Delivery”, Fibers and Polymers, Vol. 13, No. 9, pp. 1120-1125, 2012.
26. Li, Zh., and Wang, C., Dimensional Nanostructures Electrospinning Technique and Unique Nanofibers, SpringerBriefs in Materials, No. November, 2016.
27. Martins, A., Rita, A., Duarte, C., Alexandra, S. F., Rui, P. M., Reis, L., and Neves, N. M., “Biomaterials Osteogenic Induction of hBMSCs by Electrospun Scaffolds with Dexamethasone Release Functionality”, Biomaterials, Vol. 31, No. 22, pp. 5875-5885, 2010.
28. Baji, A., Mai, Y. W., Wong, S. C., Abtahi, M., and Chen, P., “Electrospinning of Polymer Nanofibers: Effects on Oriented Morphology, Structures and Tensile Properties”, Composites Science and Technology, Vol. 70, No. 5, pp. 703-718, 2010.
29. Vacanti, N. M., Cheng, H., Hill, P. S., Guerreiro, J. D., Dang, T. T., Ma, M., Watson, S., Hwang, N. S., Langer, R., and Anderson, D. G., “Localized Delivery of Dexamethasone from Electrospun Fibers Reduces the Foreign Body Response”, Biomacromolecules, Vol. 13, No. 10, pp. 3031-3038, 2012.
30. Chang, X. L., Wang, B., Liu, X., Pan, Z., Liu, Ch., Ma, H., and Jiang, L. L. & C., “The Dosage Effects of Dexamethasone on Osteogenic Activity and Biocompatibility of Poly (Lactic-co-Glycolic Acid)/ Hydroxyapatite Nanofibers”, Artificial Cells, Nanomedicine, and Biotechnology, Vol. 47, No. 1, pp. 1823-1832, 2019.

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