سنتز و بررسی نانوذرات مغناطیسی مگنتیت (Fe3O4) به منظور ارائه بهترین روش سنتز برای رهایش دارو به‌صورت کنترل‌شده در درمان انواع سرطان
محورهای موضوعی : نانوبیوتکنولوژیسید اسماعیل محمدی مهر 1 , مهدی فرامرزی 2 , سید ابوطالب موسوی پارسا 3
1 - دانشجوی دکتری، گروه مهندسی شیمی، واحد یاسوج،دانشگاه آزاد اسلامی، یاسوج، ایران
2 - استادیار، گروه مهندسی شیمی، واحد یاسوج، دانشگاه آزاد اسلامی؛ گروه مهندسی شیمی، واحد گچساران، دانشگاه آزاد اسلامی، ایران
3 - استادیار، گروه مهندسی شیمی، واحد یاسوج،دانشگاه آزاد اسلامی، یاسوج، ایران
کلید واژه: مگنتیت, نانوذرات مغناطیسی, رهایش دارو, سرطان,
چکیده مقاله :
هدف:در این تحقیق نانو ذرات با دو روش هم‌رسوبی و رسوبی - کاهشی در شرایط بهینه سنتز شدند. با استفاده از آزمون‌های X-Ray Diffraction و طیف‌سنجی مادون قرمز فوریه (FTIR) شرایط بهینه سنتز نانوذرات به روش رسوبی - کاهشی تعیین شد. در نهایت با آنالیز تصاویر گرفته شده به وسیله میکروسکوپ عبوری الکترونی از دو نمونه، متوسط اندازه نانوذرات مگنتیت سنتز شده به روش هم‌رسوبی39nm و به روش رسوبی - کاهشی 4/5nm اندازه‌گیری شد. با رسم نمودار توزیع اندازه ذره‌ای، در روش هم‌رسوبی توزیع اندازه ذره‌ای نانو ذرات نسبتاً پهن و در روش رسوبی-کاهشی توزیع اندازه ذره‌ای نسبتاً باریک بدست آمد. در نهایت با مقایسه متوسط اندازه، توزیع اندازه ذره‌ای و مورفولوژی نانوذرات سنتز شده به دو روش ذکر شده، نانوذرات مگنتیت سنتز شده به روش رسوبی- کاهشی جهت کاربردهای دارورسانی پیشنهاد می‌شوند. روش‌شناسی:این مطالعه از نوع پژوهشی شامل آزمایشات و بررسی مطالعات کتابخانه‌ای در مورد سیستم‌های رهایش دارو به صورت کنترل شده است. پس از انجام مطالعات کتابخانه‌ای و به دست آوردن اطلاعات کافی، تست‌های آزمایشگاهی این مطالعه انجام شد. نتایج:با ایجاد سیستم‌های ذره‌ای، ویژگی‌های جدیدی به داروها وارد شد که قبلاً وجود نداشت. استفاده از نانوذرات منجر به بهینه‌سازی آن شده است و ویژگی‌هایی مانند هدف درمانی، بهبود نفوذپذیری سلولی، عمر طولانی‌تر زندگی و غیره که قبلاً در زمینه داروهای معمولی در دسترس نبودند را ایجاد کرده‌‌اند. نانوذرات سنتز شده به روش رسوبی-کاهشی که در مقایسه با روش هم رسوبی دارای خلوص بالاتر، اندازه ذرات بسیار کوچک‌تر و همچنین توزیع اندازه ذره‌ای باریک‌تر هستند، با موفقیت سنتز شدند. با توجه به این که نانوذرات مگنتیت در اندازه‌های زیر 15nm خاصیت ابر پارامغناطیس از خود نشان می‌دهند و نیز نانوذرات مناسب جهت کاربردهای دارویی باید توزیع اندازه ذره‌ای یکنواختی داشته باشند، نانوذرات سنتز شده به روش رسوبی - کاهشی جهت کاربردهای دارورسانی پیشنهاد می‌شوند. نتیجه‌گیری: با توجه به این که نانوذرات مگنتیت در اندازه‌های زیر 15nm خاصیت ابرپارامغناطیس از خود نشان می‌دهند و نیز نانوذرات مناسب جهت کاربردهای دارویی باید توزیع اندازه ذره‌ای یکنواختی داشته باشند، نانوذرات سنتز شده به روش رسوبی - کاهشی جهت کاربردهای دارورسانی پیشنهاد می‌شوند.
Introduction: In this research, nanoparticles were synthesized by two methods of hemolipation and precipitation-reduction under optimal conditions. Using X-Ray Diffraction and Fourier Infrared Spectroscopy (FTIR) tests, the optimal conditions for nanoparticle synthesis were determined by sediment-reduction method. Finally, by analyzing the images taken by electron microscopy from two samples, the average size of magnetite nanoparticles synthesized by co-precipitation method was measured at 39nm and by sediment-reduction method at 4/5nm. By plotting the particle size distribution, in the co-precipitation method, the particle size distribution of nanoparticles was relatively wide and in the sediment-reduction method, the relatively narrow particle size distribution was obtained. Finally, by comparing the average size, distribution, particle size and morphology of nanoparticles synthesized by the two methods mentioned, magnetite nanoparticles synthesized by sediment-reduction method are proposed for drug delivery applications. Material and methods: This is a research study involving experiments and reviewing library studies on controlled drug delivery systems. After conducting library studies and obtaining sufficient information, laboratory tests of this study were performed. Results: With the creation of particle systems, new properties were introduced into drugs that did not exist before. The use of nanoparticles has led to its optimization and has created features such as therapeutic target, improved cell permeability, longer life, etc. that were not previously available in conventional drugs. Nanoparticles synthesized by the deposition-reduction method, which are more synthetic than the co-precipitation method, have a higher purity, a much smaller particle size, and a narrower particle size distribution. Due to the fact that magnetite nanoparticles in sizes below 15 nm show the properties of paramagnetic cloud and also nanoparticles suitable for pharmaceutical applications should have a uniform distribution of particle size, nanoparticles synthesized by sediment-reduction method are recommended for drug delivery applications. Conclusion: Due to the fact that magnetite nanoparticles in sizes below 15 nm show superparamagnetic properties and also nanoparticles suitable for pharmaceutical applications should have a uniform distribution of particle size, nanoparticles synthesized by sedimentary-reduction method for drug delivery applications are recommended.
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Bulte JWM, Kraitchman DL. Iron oxide MR contrastagent for molecular and cellular imaging. NMR Biomed. 2004; 17:484-99.
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Rana S, Gallo A, Srivastava RS, Misra RDK. On the suitability of nano ferrites as a magnetic carrier for drug delivery: Functionalization, conjugation and drug releas kinetics.Acta Biomaterialia. 2007; 3: 233-242.
Gupta Ak, gupta M. Synthesis and surface engineering of Iron oxide nanoparticles for biomedical. Applications. Biomaterials. 2005; 26: 3995-4021.
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Andrade AL, Souza DM, Ppereira MC, Fabris JD, Domingues RZ. PH efect on the synthesis of magnetite nanoparticles by the chemical reduction-percipitation method. Quim Nova, 2010; 33; 524-527.
Das M, Mishra D, Maiti TK, Basak A, Pramanik P. Bio-functionalization of magnetite nanoparticles using an aminophosphonic acid coupling agent,new Ultradispersed, iron-oxide Folate nanoconjugates for cancer-specific targeting. Nanotechnology. 2008; 19: 5101-5115
Domracheva NE, et al. Iron-containing poly(propylene imine) dendromesogens with photoactive properties. Macromol. Chem. Phys. 2010; 211: 791–800.
Fahmi A, et al. Water-soluble CdSe nanoparticles stabilised by dense-shell glycodendrimers. New J. Chem. 2009; 33: 703–706.
Oerlemans, C, Deckers R, Storm G, Hennink WE, Nijsen JFW. Evidence for a new mechanism behind HIFU-triggered release from liposomes. Journal of Controlled Release. 2013; 168(3): 327-333.
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Moghimipour E, Aghel N, Mahmoudabadi AZ, Ramezani Z, Handali S. Preparation and characterization of liposomes containing essential oil of Eucalyptus camaldulensis leaf. Jundishapur journal of natural pharmaceutical products. 2012; 7(3):117-122.
Faraji AH, Wipf P. Nanoparticles in cellular drug delivery. Bioorganic & medicinal chemistry. 2009; 17(8): 2950-2962.
Cho K, Wang X, Nie S, Shin DM. Therapeutic nanoparticles for drug delivery in cancer. Clinical cancer research. 2008; 14(5): 1310-1316.
Schwartzberg LS, Arena FP, Mintzer DM, Epperson AL, Walker MS. Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer. Clinical breast cancer. 2012; 12(2): 87-93.
_||_Moghimi SH, Hunter AC, Murray JC. Long-Circulating and target-specific nanoparticles. Pharma Rev. 2001; 53: 283-318.
Bulte JWM, Kraitchman DL. Iron oxide MR contrastagent for molecular and cellular imaging. NMR Biomed. 2004; 17:484-99.
Yoo HS, Park TG. Folate-receptor-targeted delivery of Doxorubicin nano-aggregates stabilized by Doxorubicin–PEG–folate conjugate. Journal of Controlled Release, 2004; 100: 247–256.
Sun C, Lee JSH, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Advanced Drug Delivery Reviews. 2008; 60: 1252–1265.
Rana S, Gallo A, Srivastava RS, Misra RDK. On the suitability of nano ferrites as a magnetic carrier for drug delivery: Functionalization, conjugation and drug releas kinetics.Acta Biomaterialia. 2007; 3: 233-242.
Gupta Ak, gupta M. Synthesis and surface engineering of Iron oxide nanoparticles for biomedical. Applications. Biomaterials. 2005; 26: 3995-4021.
Choi H, Choi SR, Zhou R, Kung HF, Weichen I. Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery. Acad Radiol. 2004; 11: 996-1004.
Arbab AS, Bashaw LA, Miller BR, Jordan EK, Lewis BK, Kalish H, Frank JA. Characterization of biophysical and metabolicproperties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology. 2003; 229(3): 838–846.
Pankhurst QA, Connolly J, Jones SK, Dobson J. Applications of magnetic nanoparticles in biomedicine. J Phys D Appl Phys. 2003; 36: 167–181.
Guo Sh, Li D, Zhang L, Li J, Wang E. Monodisperse mesoporous supermagnetic single-crystal magnetite nanoparticles for drug delivery. Biomaterials.2009; 30: 1881-1889.
Zhang Y, Kohler N, Zhang M. Surface modification of superparamagnetic magnetite nano particles and their intracellular uptake. Biomaterials. 2002; 23: 1553–1561.
Meng JH, Yang GQ, Yan LM, Wang XU. Synthesis and characterization of magnetic. nanometer pigment Fe3O4. Dyes and Pigment. 2005; 66: 109-113.
Lu AH, Salabas EL, Schüth F. Magnetic Nanoparticles: synthesis, porotection, functionalization, and application. Angew Chem Int Ed. 2007; 46: 1222-1244.
Jain TK, Morales MA, Sahood SK, Leslie-Pelecky L, Labhasetwar V. Iron oxide nanoparticles for sustained delivery of anti cancer agent. Mol Pharm. 2005; 2: 194-205.
Shengchun Qu, Yang H, Ren D, Kan S, Zou G, Li D, Li M. Magnetite nanoparticles prepared by precipitation from partially reduced ferric chloride aqueous solutions. Journal of Colloid and Interface Science. 1999; 215: 190–192.
Forge D, Roch A, Laurent S, Tellez H, Gossuin Y, Renaux F, Elst LV, Muller RN. Optimization of the synthesis of superparamagnetic contrast agents by the design of experiments method. J.Phys.Chem.2008; 112: 19178–19185.
Andrade AL, Souza DM, Ppereira MC, Fabris JD, Domingues RZ. PH efect on the synthesis of magnetite nanoparticles by the chemical reduction-percipitation method. Quim Nova, 2010; 33; 524-527.
Das M, Mishra D, Maiti TK, Basak A, Pramanik P. Bio-functionalization of magnetite nanoparticles using an aminophosphonic acid coupling agent,new Ultradispersed, iron-oxide Folate nanoconjugates for cancer-specific targeting. Nanotechnology. 2008; 19: 5101-5115
Domracheva NE, et al. Iron-containing poly(propylene imine) dendromesogens with photoactive properties. Macromol. Chem. Phys. 2010; 211: 791–800.
Fahmi A, et al. Water-soluble CdSe nanoparticles stabilised by dense-shell glycodendrimers. New J. Chem. 2009; 33: 703–706.
Oerlemans, C, Deckers R, Storm G, Hennink WE, Nijsen JFW. Evidence for a new mechanism behind HIFU-triggered release from liposomes. Journal of Controlled Release. 2013; 168(3): 327-333.
Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nature materials. 2013; 12(11): 991-1003.
Hirsjarvi S, Passirani C. Benoit JP.Passive and active tumour targeting with nanocarriers. Current drug discovery technologies. 2011; 8(3): 188-196.
Gu FX, et al. Targeted nanoparticles for cancer therapy. Nano today. 2007; 2(3): 14-21.
Abou-Jawde R, Choueiri T, Alemany C, Mekhail T. An overview of targeted treatments in cancer. Clinical therapeutics. 2003; 25(8): 2121-2137.
Vogel CL, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. Journal of Clinical Oncology. 2002; 20(3): 719-726.
Moghimipour E, Aghel N, Mahmoudabadi AZ, Ramezani Z, Handali S. Preparation and characterization of liposomes containing essential oil of Eucalyptus camaldulensis leaf. Jundishapur journal of natural pharmaceutical products. 2012; 7(3):117-122.
Faraji AH, Wipf P. Nanoparticles in cellular drug delivery. Bioorganic & medicinal chemistry. 2009; 17(8): 2950-2962.
Cho K, Wang X, Nie S, Shin DM. Therapeutic nanoparticles for drug delivery in cancer. Clinical cancer research. 2008; 14(5): 1310-1316.
Schwartzberg LS, Arena FP, Mintzer DM, Epperson AL, Walker MS. Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer. Clinical breast cancer. 2012; 12(2): 87-93.