Controlled release of anticancer drugs via the magnetic magnesium iron nanoparticles modified by graphene oxide and polyvinyl alcohol: Paclitaxel and docetaxel

Document Type : Research Paper


1 Electroanalytical Chemistry Laboratory, Department of Chemistry, Faculty of Sciences, Azarbaijan Shahid Madani University, Tabriz 53714-161, Iran

2 Department of Applied Chemistry, Faculty of Chemistry, Urmia University, Urmia, Iran

3 Chromatogrphy Laboratory, Department of Chemistry, Faculty of Sciences, Azarbaijan Shahid Madani University, Tabriz 53714-161, Iran

4 Analytical Spectroscopy Research Laboratory, Department of Chemistry, Faculty of Science, Urmia University, 1177, Urmia, Iran


Objective(s): Paclitaxel (PTX) and docetaxel (DTX) belong to the family of taxanes drugs which have been employed for treatment of ovarian, breast, lung, head, neck, gastric, pancreatic, bladder, prostate and cervical cancer. Controlled drug release systems improve the effectiveness of drug therapy by modifying the release profile, biodistribution, stability and solubility, bioavailability of drugs and minimize the side effects of anticancer drugs. So, the purpose of the present study was to synthesize the modified nanocomposite for the controlled releases of these drugs.
Materials and Methods: Magnetic magnesium iron oxide nanoparticles were synthesized via the co-precipitation chemical method and then composited with graphene oxide and modified by polyvinyl alcohol. The physicochemical characterization of the prepared nanocomposites was investigated by scanning electron microscope (SEM),  X-ray powder diffraction (XRD) , Fourier-transform infrared spectroscopy and vibrating-sample magnetometer.
Results: Specific characteristics such as adsorption capacity, monodispersity, stability and hydrophilicity of magnetic nanomaterials were studied in the controlled release of anticancer drugs. Drug loading content and drug loading efficiency and release rate of drugs were investigated in vitro at different pH with ultraviolet-visible spectroscopy (UV-Vis). DLE and DLC of PTX and DTX in the modified magnetic nanocomposites were calculated  as 85.2 ± 2.7% and 7.74 ± 0.24% , 89.4 ± 1.2% and 8.12 ± 0.11% of, respectively. The cumulative release amount of PTX and DTX from magnetic modified nanocomposites at pHs 5.8, 7.4 over 100 h were 58 % and 40 % and 54 % and 37 %, respectively.
Conclusion: The potential of modified nanocomposite in drug delivery systems from the intrinsic properties of the magnetic core combined with their drug loading capability and the biomedical properties of modified nanocomposite generated by different surface coatings. The generally sustained and controlled release profile of DTX (or PTX) facilitates the application of modified nanocomposite for the delivery of anticancer drugs.


1. Xianbo M, Zeeshan A, Song L, Nongyue H. Applications of Magnetic Nanoparticles in Targeted Drug Delivery System. J Nanosci Nanotechnol. 2015; 15(1): 54-62.
2. Chomoucka J, Drbohlavova J, Huska D, Adam V, Kizek R, Hubalek J. Magnetic nanoparticles and targeted drug delivering. Pharmacol Res. 2010; 62(2): 144-149.
3. Gholami A , Mousavi SM, Hashemi SA, Ghasemi Y, Chiang WH, Parvin N. Current trends in chemical modifications of magnetic nanoparticles for targeted drug delivery in cancer chemotherapy. Drug Metab Rev. 2020; 52(1): 205-224.
4. Fernando R, Downs J, Maples D, Ranjan A. MRI-Guided Monitoring of Thermal Dose and Targeted Drug Delivery for Cancer Therapy. Pharm Res. 2013; 30: 2709-2717.
5. Reddy LH, Arias JL, Nicolas J, Couvreur P. Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chemical Reviews. 2012; 112(11): 5818-5878.
6. Antic B, Jovic N, Pavlovic MB, Kremenovic A, Manojlovic D, Vasic MV, et al. Magnetization enhancement in nanostructured random type MgFe2O4 spinel prepared by soft mechanochemical route. J Appl Phys. 2010; 107(4): 043525.
7. Shahid M, Jingling L, Ali Z, Shakir I, Warsi MF, Parveen R, et al. Photocatalytic degradation of methylene blue on magnetically separable MgFe2O4 under visible light irradiation. Mater Chem Phys. 2013; 139(2-3): 566-571.
8. Yang G, Li X, Zhao Z, Wang W. Preparation, characterization, in vivo and in vitro studies of arsenic trioxide Mg-Fe ferrite magnetic nanoparticles. Acta Pharmacol Sin. 2009; 30: 1688-1693.
9. Khot VM, Salunkhe AB, Thorat ND, Ningthoujam RS, Pawar SH. Induction heating studies of dextran coated MgFe2O4nanoparticles for magnetic hyperthermia. Dal Trans. 2013;42:1249-1258.
10. Harish KN, Bhojya Naik HS, Prashanth Kumar PN, Viswanath R. Optical and photocatalytic properties of solar light active Nd-substituted Ni ferrite catalysts: for environmental protection. ACS Sustain Chem Eng. 2013; 9(1): 1143-1153.
11. Pan Y, Zhang Y, Wei X, Yuan C, Yin J, Cao D, et al.. MgFe2O4 nanoparticles as anode materials for lithium-ion batteries. Electrochim Acta. 2013; 109: 89-94.
12. Sepahvand R, Mohammadzadeh R. Synthesis and Characterization of Carbon Nanotubes Decorated with Magnesium Ferrite (MgFe2O4) Nanoparticles by Citrate-Gel Method. J Scie Islamic Rep Iran. 2011; 22(2): 177-182.
13. Dideikin AT, Vul AY. Graphene Oxide and Derivatives: The Place in Graphene Family. Front Phys. 2019; 6: 149-149.
14. Javed H, Rehman A, Mussadiq S, Shahid M, Azhar Khan M, Shakir I, et al.. Reduced graphene oxide-spinel ferrite nano-hybrids as magnetically separable and recyclable visible light driven photocatalyst. Synt Metals. 2019; 254: 1-9.
15. Marcano DC, Kosynkin DV, Berlin JM, Sinitskii A, Sun Z, Slesarev A, et al. Improved Synthesis of Graphene Oxide. ACS Nano. 2010; 8(4): 4806-4814
16. Rai AK, Gim J, Anh LT, Kim J. Partially reduced Co3O4/graphene nanocomposite as an anode material for secondary lithium ion battery. Electrochim Acta. 2013; 100: 63-71.
17. Stankovich S, Dikin DA, Dommett GH, Kohlhaas KM, Zimney EJ, Stach EA, et al. Graphene-based composite materials. Nature. 2006; 442(20): 282-286.
18. Deng X, Lü L, Li H, Luo F. The adsorption properties of Pb(II) and Cd(II) on functionalized graphene prepared by electrolysis method. J Hazard mater. 2010; 183(1-3): 923-930.
19. Harivardhan Reddy L, Arias JL, Nicolas J, Couvreur P. Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications.Chem Rev. 2012; 112(4): 5818-5878.
20. Moulay S. Review: Poly(vinyl alcohol) Functionalizations and Applications. Polym Plast Technol Eng. 2015; 54(12): 1289-1319.
21. Aisida SO, Ahmad I, Zhao Tk, Maaza M, Ezema FI. Calcination Effect on the Photoluminescence, Optical, Structural, and Magnetic Properties of Polyvinyl Alcohol Doped ZnFe2O4 Nanoparticles. J Macromol Sci B. Phys. 2020; 59(5): 295-308.
22. Mohsen-Nia M, Modarress H. Viscometric study of aqueous poly(vinyl alcohol) (PVA) solutions as a binder in adhesive formulations. J Adhes Sci Technol.2006; 20: 1273-1280.
23. Paradossi G, Cavalieri F, Chiessi E, Spagnoli C, Cowman MK. Poly(vinyl alcohol) as versatile biomaterial for potential biomedical applications. J Mater Sci: Mater Medi. 2003; 14(8): 687-691.
24. Musetti A, Paderni K, Fabbri P, Pulvirenti A, Al-Moghazy M, Fava P. Poly(vinyl alcohol)‐Based Film Potentially Suitable for Antimicrobial Packaging Applications. J Food Sci. 2014; 79: E577-E582.
25. Hyon SH, Cha WI, Ikada Y, Kita M, Ogura Y, Honda Y. Poly(vinyl alcohol) hydrogels as soft contact lens material. J Biomater Sci, Poly E.1994; 5(5): 397-406.
26. Zhang J, Wang J, Lin T, Wang CH, Ghorbani K, Fang J, et al. Magnetic and mechanical properties of polyvinyl alcohol (PVA) nanocomposites with hybrid nanofillers - Graphene oxide tethered with magnetic Fe3O4 nanoparticles. Chem Eng J. 2014; 237: 462-468.
27. Qiu XP, Winnik F. Preparation and characterization of PVA coated magnetic nanoparticles. Chin J Poly Sci. 2000; 18: 535-539.
28. Kim SY, Ramaraj B, Yoon KR. Preparation and characterization of polyvinyl alcohol‐grafted Fe3O4 magnetic nanoparticles through glutaraldehyde. Surf Inter Anal 2012; 44(9): 1238-1242.
29. Maleki A, Niksefat M, Rahimi J, Hajizadeh Z. Design and preparation of Fe3O4@PVA polymeric magnetic nanocomposite film and surface coating by sulfonic acid via in situ methods and evaluation of its catalytic performance in the synthesis of dihydropyrimidines. BMC Chem. 2019; 13: 19.
30. Mosiniewicz-Szablewska E, Clavijo AR, Castilho APOR, Paterno LG, Pereira-da-Silva MA, Więckowski J, et al. Magnetic studies of layer-by-layer assembled polyvinyl alcohol/iron oxide nanofilms. Phys Chem Chem Phys.2018; 20: 26696-26709.
31. Dobson J. Magnetic nanoparticles for drug delivery. Drug Develop Res. 2006; 67(1): 55-60.
32. Subramani K, Hosseinkhani H, Khraisat A, Hosseinkhani M, Pathak Y. Targeting Nanoparticles as Drug Delivery Systems for Cancer Treatment. Cur Nanosci. 2009; 5(2): 135-140.
33. Chomoucka J, Drbohlavova J, Huskab D, Adam V, Kizek R, Hubalek J. Magnetic nanoparticles and targeted drug delivering. Pharm Res. 2010; 62(2): 144-149.
34. Mukherjee S, Liang L, Veiseh O. Recent Advancements of Magnetic Nanomaterials in Cancer Therapy. Pharmaceutics 2020: 12(2): 147.
35. Swai H, Semete B, Kalombo L, Chelule P, Kisich K, Sievers B. Nanoparticulate alternatives for drug delivery. WIRES Nanomed Nanobio.2009; 1(3): 255-263.
36. Faraji A, Wipf P. Nanoparticles in cellular drug delivery. Bio Medi Chem. 2009; 17(8): 2950-2962.
37. Lin Z, Gao W, Hu H, Ma K, He B, Dai W, et al. Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity. J Control Release. 2014; 174: 161-170.
38. Conte C, Ungaro F, Maglio G, Tirino P, Siracusano G, Sciortino MT, et al. Biodegradable core-shell nanoassemblies for the delivery of docetaxel and Zn(II)-phthalocyanine inspired by combination therapy for cancer. J Control Release. 2013; 167(1): 40-52.
39. Kim SC, Kim DW, Shim YH, Bang JS, Oh HS, Kim SW, et al. In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. J Control Release. 2001; 72 (1-3): 191-202.
40. Zhao P, Astruc D. Docetaxel Nanotechnology in Anticancer Therapy.ChemMedChem. 2012; 7: 952-972.
41. Feng SS, Huang G. Effects of emulsifiers on the controlled release of paclitaxel (Taxol®) from nanospheres of biodegradable polymers. J Control Release. 2001; 71(1): 53-69.
42. Mu L, Feng SS. PLGA/TPGS Nanoparticles for Controlled Release of Paclitaxel: Effects of the Emulsifier and Drug Loading Ratio. Pharm Res. 2003; 20: 1864-1872.
43. Ruan G, Feng SS. Preparation and characterization of poly(lactic acid)–poly(ethylene glycol)–poly(lactic acid) (PLA–PEG–PLA) microspheres for controlled release of paclitaxel. Biomater. 2003; 24(27): 5037-5044.
44. Farboudi A, Nouri A, Shirinzad S, Sojoudi P, Davaran S, Akrami M, et al. Synthesis of magnetic gold coated poly (ε-caprolactonediol) based polyurethane/poly(N-isopropylacrylamide)-grafted-chitosan core-shell nanofibers for controlled release of paclitaxel and 5-FU. Inter J Biolog Macromol. 2020; 150: 1130-1140.
45. Bikiaris ND, Ainali NM, Christodoulou E, Kostoglou M, Kehagias T, Papasouli E, et al. Dissolution Enhancement and Controlled Release of Paclitaxel Drug via a Hybrid Nanocarrier Based on mPEG-PCL Amphiphilic Copolymer and Fe-BTC Porous Metal-Organic Framework. Nanomater 2020; 10(12): 2490.
46. Lee S, Miyajima T, Sugawara-Narutaki A, Kato K, Nagata F. Development of paclitaxel-loaded poly(lacticacid)/hydroxyapatite core-shell nanoparticles as a stimuli -responsive drug delivery system. R Soc Open Sci. 2021; 8: 202030.
47. Agrawal R, Shanavas A, Yadav S, Aslam M, Bahadur D, Srivastava R. Polyelectrolyte Coated Polymeric Nanoparticles for Controlled Release of Docetaxel. J Biomed Nanotechnol. 2012; 8(1): 19-28.
48. Musumeci T, Ventura CA, Giannone I, Ruozi B, Montenegro L, Pignatello R, et al. PLA/PLGA nanoparticles for sustained release of docetaxel. Inter J Pharm. 2006; 325(1-2): 172-179.
49. Wang W, Chen S, Zhang L, Wu X, Wang J, Chen JF, et al. Poly(lactic acid)/chitosan hybrid nanoparticles for controlled release of anticancer drug. Mater Sci Eng: C. 2015; 46: 514-520.
50. Karimi N, Soleiman-Beigi M, Fattahi A. Co-delivery of all-trans-retinoic acid and docetaxel in drug conjugated polymeric nanoparticles: Improving controlled release and anticancer effect. Mater Today Commun. 2020; 25: 101280.
51. Faisalina AF, Sonvico F, Colombo P, Amirul AA, Wahab HA, Abdul Majid MI. Docetaxel-Loaded Poly(3HB-co-4HB) Biodegradable Nanoparticles: Impact of Copolymer Composition. Nanomater 2020; 10(11): 2123.
52. Wang X, Cheng R, Zhong Z. Facile fabrication of robust, hyaluronic acid-surfaced and disulfide-crosslinked PLGA nanoparticles for tumor-targeted and reduction-triggered release of docetaxel. Acta Biomater. 2021; 125(15): 280-289.
53. Ashrafizadeh M, Ahmadi Z, Mohamadi N, Zarrabi A, Abasi S, Dehghannoudeh G, et al. Chitosan-based advanced materials for docetaxel and paclitaxel delivery: Recent advances and future directions in cancer theranostics. Inter J Biolog Macromol. 2020; 145: 282-300.
54. Etrych T, Šírová M, Starovoytova L., Říhová B Ulbrich, K. HPMA Copolymer Conjugates of Paclitaxel and Docetaxel with pH-Controlled Drug Release. Molecul Pharm. 2010; 7(4): 1015-1026.
55. Ali R, Khan MA, Mahmood A, Chughtai AH, Sultan A, Shahid M, et al. Structural, magnetic and dielectric behavior of Mg1−xCaxNiyFe2−yO4 nano-ferrites synthesized by the micro-emulsion method. Ceram Inter. 2014; 40(3): 3841-3846.
56. Hummers WS, Offeman RE. Preparation of Graphitic Oxide. J Am Chem Soc. 1958; 80(6): 1339-1339.
57. Shakir I, Sarfraz M, Ali Z, Aboud MFA, Agboola PO. Magnetically separable and recyclable graphene-MgFe2O4 nanocomposites for enhanced photocatalytic applications. J Alloy Comp. 2016; 660: 450-455.
58. Tarhan T, Tural B, Tural S. Synthesis and characterization of new branched magnetic nanocomposite for loading and release of topotecan anti-cancer drug. J Anal Sci Tech. 2019; 30(10): 1-13.
59. Feng S-S, Mei L, Anitha P, Gan CW, Zhou W. Poly(lactide)–vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel. Biomater. 2009; 30(19): 3297-3306.
60. Yin Y-M, Cui F-D, Mu C-F, Choi M-K, Kim JS, Chung S-J, et al. Docetaxel microemulsion for enhanced oral bioavailability: preparation and in vitro and in vivo evaluation. J Control Release. 2009; 140(2): 86-94.
61. Zhou H, Hu L, Wan J, Yang R, Yu X, Li H, et al. Microwave-enhanced catalytic degradation of p-nitrophenol in soil using MgFe2O4. Chem Eng J. 2016; 284: 54-60.
62. Nguyen LTT, Nguyen LTH, Manh NC, Quoc DN, Quang HN, Nguyen HTT, et al. A Facile Synthesis, Characterization, and Photocatalytic Activity of Magnesium Ferrite Nanoparticles via the Solution Combustion Method. J Chem. 2019; 2019:Article ID 3428681.
63. Reddy MP, Zhou XB, Huang Q, Ramakrishna Reddy R. Synthesis and Characterization of Ultrafine and Porous Structure of Magnesium Ferrite Nanospheres. Inter J Nano StudTechnol. 2014; 3(6): 72-77.
64. Chandradass J, Jadhav AH, Kim KH, Kim H. Influence of processing methodology on the structural and magnetic behavior of MgFe2O4 nanopowders. J Alloy Compounds. 2012; 517: 164-169.
65. Nasar G, Magnesium ferrite/polyvinyl alcohol (PVA) nanocomposites: Fabrication and characterization. J Nanomater Mol Nanotechnol. 2019;DOI: 10.4172/2324-8777-C4-065.
66. Zheng L, Fang K, Zhang M, Nan Z, Zhao L, Zhou D, Zhu M, Li W. Tuning of spinel magnesium ferrite nanoparticles with enhanced magnetic properties. RSC Adv. 2018; 8: 39177-39181.
67. Li YF, Liu YZ, Zhang WK, Guo CY, Chen CM. Green synthesis of reduced graphene oxide paper using Zn powder for supercapacitors. Mater Let. 2015; 157: 273-276.
68. Rai AK, Thi TV, Gim J, Kim J. Combustion synthesis of MgFe2O4/graphene nanocomposite as a high-performance negative electrode for lithium ion batteries. Mater Charact. 2014; 95: 259-265.