Advertisement

Journal of Materials Science

, Volume 54, Issue 13, pp 9689–9706 | Cite as

A doxorubicin and vincristine drug release system based on magnetic PLGA microspheres prepared by coaxial electrospray

  • Yajun Tang
  • He Zhao
  • Jihang Yao
  • Zhenhua Zhu
  • Dahui Sun
  • Mei ZhangEmail author
Materials for life sciences
  • 19 Downloads

Abstract

In this study, we demonstrated a novel doxorubicin and vincristine-loaded PLGA magnetic microspheres prepared by coaxial electrospray, as a drug delivery system for osteosarcoma treatment. The results showed that microspheres had an minimum mean diameter of 0.32 ± 0.25 μm and exhibited a spherical shape. The particle size distribution changed obviously with the different dosing ways. The entrapment efficiency was found to be 65.72, 73.6 and 74.14% for different microspheres. In vitro degradation research showed that circular pores appeared gradually on the surface of particles with the increase in time, which accelerated the degradation of microspheres. CCK-8 test showed that the Fe3O4@PLGA microspheres without drug loading had almost no side effects, the cytotoxicity of Fe3O4@P/(V + D), Fe3O4@(P + D)/V and Fe3O4@(P + V)/D microspheres increased in turn, and Fe3O4@(P + V)/D microspheres with minimum particle size could significantly arrest the growth of osteosarcoma saos-2 cells. Therefore, the drug-loaded magnetic microspheres have good killing effect on osteosarcoma cell lines, which can be used as an ideal targeting treatment for postoperative adjuvant therapy of osteosarcoma.

Notes

Acknowledgements

The work was supported by Jilin Province Health Project 2018 (3D517EB73428) and Key Project of Science and Technology Development Plan, Jilin Province of China (20170204042GX).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10853_2019_3575_MOESM1_ESM.docx (1.3 mb)
Supplementary material 1 (DOCX 1283 kb)

References

  1. 1.
    American Cancer Society (2016) Cancer facts & figures 2016, cancer facts fig. 2016., pp 1–9.  https://doi.org/10.1097/01.NNR.0000289503.22414.79 Google Scholar
  2. 2.
    American Cancer Society (2018) Cancer facts & figures 2018. American Cancer Society, Atlanta.  https://doi.org/10.3322/caac.21442 Google Scholar
  3. 3.
    Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, Yang Z, Li H, Zou X, He J (2018) Cancer incidence and mortality in China, 2014. Chin J Cancer Res 30(2018):1–12.  https://doi.org/10.21147/j.issn.1000-9604.2018.01.01 CrossRefGoogle Scholar
  4. 4.
    Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China. CA Cancer J Clin 66:115–132.  https://doi.org/10.3322/caac.21338 CrossRefGoogle Scholar
  5. 5.
    Unni KK, Inwards CY, Dahlin DC (1996) Dahlin’s bone tumors: general aspects and data on 10,165 cases. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  6. 6.
    Hussien NA, Işıklan N, Türk M (2018) Aptamer-functionalized magnetic graphene oxide nanocarrier for targeted drug delivery of paclitaxel. J Mater Chem Phys 211:479–488.  https://doi.org/10.1016/J.MATCHEMPHYS.2018.03.015 CrossRefGoogle Scholar
  7. 7.
    Ji RC (2014) Hypoxia and lymphangiogenesis in tumor microenvironment and metastasis. J Cancer Lett 346:6–16.  https://doi.org/10.1016/j.canlet.2013.12.001 CrossRefGoogle Scholar
  8. 8.
    Ahmad H, Nurunnabi M, Rahman MM, Kumar K, Tauer K, Minami H, Gafur MA (2014) Magnetically doped multi stimuli-responsive hydrogel microspheres with IPN structure and application in dye removal. J Colloids Surf A Physicochem Eng Asp 459:39–47.  https://doi.org/10.1016/j.colsurfa.2014.06.038 CrossRefGoogle Scholar
  9. 9.
    Klinger D, Landfester K (2012) Stimuli-responsive microgels for the loading and release of functional compounds: fundamental concepts and applications. J Polym 53:5209–5231.  https://doi.org/10.1016/j.polymer.2012.08.053 CrossRefGoogle Scholar
  10. 10.
    Motornov M, Roiter Y, Tokarev I, Minko S (2010) Stimuli-responsive nanoparticles, nanogels and capsules for integrated multifunctional intelligent systems. J Prog Polym Sci 35:174–211.  https://doi.org/10.1016/j.progpolymsci.2009.10.004 CrossRefGoogle Scholar
  11. 11.
    Sun X, Shi J, Xu X, Cao S (2013) Chitosan coated alginate/poly(N-isopropylacrylamide) beads for dual responsive drug delivery. J Int J Biol Macromol 59:273–281.  https://doi.org/10.1016/j.ijbiomac.2013.04.066 CrossRefGoogle Scholar
  12. 12.
    Jaber J, Mohsen E (2013) Synthesis of Fe3O4@silica/poly(N-isopropylacrylamide) as a novel thermo-responsive system for controlled release of H3PMo12O40 nano drug in AC magnetic field. J Colloids Surf B Biointerfaces 102:265–272.  https://doi.org/10.1016/j.colsurfb.2012.08.024 CrossRefGoogle Scholar
  13. 13.
    Fang K, Song L, Gu Z, Yang F, Zhang Y, Gu N (2015) Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy. J Colloids Surf B Biointerfaces 136:712–720.  https://doi.org/10.1016/j.colsurfb.2015.10.014 CrossRefGoogle Scholar
  14. 14.
    Lin X, Yang H, Su L, Yang Z, Tang X (2018) Effect of size on the in vitro/in vivo drug release and degradation of exenatide-loaded PLGA microspheres. J Drug Deliv Sci Technol 45:346–356.  https://doi.org/10.1016/j.jddst.2018.03.024 CrossRefGoogle Scholar
  15. 15.
    Malik SA, Ng WH, Bowen J, Tang J, Gomez A, Kenyon AJ, Day RM (2016) Electrospray synthesis and properties of hierarchically structured PLGA TIPS microspheres for use as controlled release technologies. J Colloid Interface Sci 467:220–229.  https://doi.org/10.1016/j.jcis.2016.01.021 CrossRefGoogle Scholar
  16. 16.
    Kuboyama T, Yokoshima S, Tokuyama H, Fukuyama T (2004) Stereocontrolled total synthesis of (+)-Vincristine. J Proc Natl Acad Sci USA 101:11966–11970.  https://doi.org/10.1073/pnas.0401323101 CrossRefGoogle Scholar
  17. 17.
    Jordan M (2002) Mechanism of action of antitumor drugs that interact with microtubules and tubulin. J Curr Med Chem Agents 2:1–17.  https://doi.org/10.2174/1568011023354290 CrossRefGoogle Scholar
  18. 18.
    Silverman JA, Deitcher SR (2013) Marqibo® (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. J Cancer Chemotherapy Pharmacol 71:555–564.  https://doi.org/10.1007/s00280-012-2042-4 CrossRefGoogle Scholar
  19. 19.
    Tacar O, Sriamornsak P, Dass CR (2013) Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65:157–170.  https://doi.org/10.1111/j.2042-7158.2012.01567.x CrossRefGoogle Scholar
  20. 20.
    Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA (1994) Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. J Mol Pharmacol 45:649–656Google Scholar
  21. 21.
    Pommier Y, Leo E, Zhang H, Marchand C (2010) DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. J Chem Biol 17:421–433.  https://doi.org/10.1016/j.chembiol.2010.04.012 CrossRefGoogle Scholar
  22. 22.
    Tacar O, Sriamornsak P, Dass CR (2013) Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65:157–170.  https://doi.org/10.1111/j.2042-7158.2012.01567.x CrossRefGoogle Scholar
  23. 23.
    Jones SE, Durie BGM, Salmon SE (1975) Combination chemotherapy with adriamycin and cyclophosphamide for advance breast cancer. J Cancer 36:90–97.  https://doi.org/10.1002/1097-0142(197507)36:1%3c90:AID-CNCR2820360104%3e3.0.CO;2-H CrossRefGoogle Scholar
  24. 24.
    Suryanarayan K, Natkunam Y, Berry G, Bangs CD, Cherry A, Dahl G (2001) Modified cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone therapy for postransplantation lymphoproliferative disease in pediatric patients undergoing solid organ transplantation. J Pediatr Hematol Off J Am Soc Pediatr Hematol 23:452–455.  https://doi.org/10.1097/00043426-200110000-00012 CrossRefGoogle Scholar
  25. 25.
    Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large -B-cell lymphoma. J N Engl J Med 346:235–242.  https://doi.org/10.1056/NEJMoa011795 CrossRefGoogle Scholar
  26. 26.
    Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, De Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V (2007) Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin’s lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 25:3495–3502.  https://doi.org/10.1200/JCO.2006.07.0482 CrossRefGoogle Scholar
  27. 27.
    Mei F, Chen DR (2007) Investigation of compound jet electrospray: particle encapsulation. J Phys Fluids.  https://doi.org/10.1063/1.2775976 Google Scholar
  28. 28.
    Xie J, Lim LK, Phua Y, Hua J, Wang CH (2006) Electrohydrodynamic atomization for biodegradable polymeric particle production. J Colloid Interface Sci 302:103–112.  https://doi.org/10.1016/j.jcis.2006.06.037 CrossRefGoogle Scholar
  29. 29.
    Bai J, Li Y, Li M, Gao J, Zhang X, Wang S, Zhang C, Yang Q (2008) A novel approach to prepare AgCl/PVP nanocomposite microspheres via electrospinning with sol-gel method. J Colloids Surf A Physicochem Eng Asp 318:259–262.  https://doi.org/10.1016/j.colsurfa.2007.12.055 CrossRefGoogle Scholar
  30. 30.
    Zhang S, Kawakami K (2010) One-step preparation of chitosan solid nanoparticles by electrospray deposition. J Int J Pharm 397:211–217.  https://doi.org/10.1016/j.ijpharm.2010.07.007 CrossRefGoogle Scholar
  31. 31.
    Sander C, Nielsen HM, Jacobsen J (2013) Buccal delivery of metformin: TR146 cell culture model evaluating the use of bioadhesive chitosan discs for drug permeability enhancement. J Int J Pharm 458:254–261.  https://doi.org/10.1016/j.ijpharm.2013.10.026 CrossRefGoogle Scholar
  32. 32.
    Zauner W, Farrow NA, Haines AM (2001) In vitro uptake of polystyrene microspheres: effect of particle size, cell line and cell density. J J Control Release. 71:39–51.  https://doi.org/10.1016/S0168-3659(00)00358-8 CrossRefGoogle Scholar
  33. 33.
    Fang H, Ma CY, Wan TL, Zhang M, Shi WH (2007) Fabrication of monodisperse magnetic Fe3O4–SiO2 nanocomposites with core-shell structures. J Phys Chem C 111:1065–1070.  https://doi.org/10.1021/jp0672048 CrossRefGoogle Scholar
  34. 34.
    Wang X, Jing X, Zhang X, Liu Q, Liu J, Song D, Wang J, Liu L (2016) A versatile platform of magnetic microspheres loaded with dual-anticancer drugs for drug release. J Mater Chem Phys 177:213–219.  https://doi.org/10.1016/j.matchemphys.2016.04.021 CrossRefGoogle Scholar
  35. 35.
    Seju U, Kumar A, Sawant KK (2011) Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies. J Acta Biomater 7:4169–4176.  https://doi.org/10.1016/j.actbio.2011.07.025 CrossRefGoogle Scholar
  36. 36.
    Rana S, Gallo A, Srivastava RS, Misra RDK (2007) On the suitability of nanocrystalline ferrites as a magnetic carrier for drug delivery: functionalization, conjugation and drug release kinetics. J Acta Biomater 3:233–242.  https://doi.org/10.1016/j.actbio.2006.10.006 CrossRefGoogle Scholar
  37. 37.
    Mosafer J, Abnous K, Tafaghodi M, Jafarzadeh H, Ramezani M (2017) Preparation and characterization of uniform-sized PLGA nanospheres encapsulated with oleic acid-coated magnetic-Fe3O4 nanoparticles for simultaneous diagnostic and therapeutic applications. J Colloids Surf A Physicochem Eng Asp 514:146–154.  https://doi.org/10.1016/j.colsurfa.2016.11.056 CrossRefGoogle Scholar
  38. 38.
    Mosafer J, Teymouri M, Abnous K, Tafaghodi M, Ramezani M (2017) Study and evaluation of nucleolin-targeted delivery of magnetic PLGA-PEG nanospheres loaded with doxorubicin to C6 glioma cells compared with low nucleolin-expressing L929 cells. J Mater Sci Eng C 72:123–133.  https://doi.org/10.1016/j.msec.2016.11.053 CrossRefGoogle Scholar
  39. 39.
    Lee DK, Kang YS, Lee CS, Stroeve P (2002) Structure and characterization of nanocomposite Langmuir–Blodgett films of poly (maleic monoester)/Fe3O4 nanoparticle complexes. J Phys Chem B 106:7267–7271.  https://doi.org/10.1021/jp014446t CrossRefGoogle Scholar
  40. 40.
    Huang CL, Hsieh WJ, Lin CW, Yang HW, Wang CK (2018) Multifunctional liposomal drug delivery with dual probes of magnetic resonance and fluorescence imaging. J Ceram Int 99:1–9.  https://doi.org/10.1016/j.ceramint.2018.04.034 Google Scholar
  41. 41.
    Hyun DC (2015) Magnetically-controlled, pulsatile drug release from poly(ε-caprolactone) (PCL) particles with hollow interiors. J Polym 74:159–165.  https://doi.org/10.1016/j.polymer.2015.07.038 CrossRefGoogle Scholar
  42. 42.
    Zhang P, Ling G, Sun J, Zhang T, Yuan Y, Sun Y, Wang Z, He Z (2011) Multifunctional nanoassemblies for vincristine sulfate delivery to overcome multidrug resistance by escaping P-glycoprotein mediated efflux. J Biomater 32:5524–5533.  https://doi.org/10.1016/j.biomaterials.2011.04.022 CrossRefGoogle Scholar
  43. 43.
    Ling G, Zhang P, Zhang W, Sun J, Meng X, Qin Y, Deng Y, He Z (2010) Development of novel self-assembled DS-PLGA hybrid nanoparticles for improving oral bioavailability of vincristine sulfate by P-gp inhibition. J Control Release 148:241–248.  https://doi.org/10.1016/j.jconrel.2010.08.010 CrossRefGoogle Scholar
  44. 44.
    Rescignano N, Tarpani L, Romani A, Bicchi I, Mattioli S, Emiliani C, Torre L, Kenny JM, Martino S, Latterini L, Armentano I (2016) In-vitro degradation of PLGA nanoparticles in aqueous medium and in stem cell cultures by monitoring the cargo fluorescence spectrum. J Polym Degrad Stab 134:296–304.  https://doi.org/10.1016/j.polymdegradstab.2016.10.017 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Alan G. MacDiarmid Laboratory, College of ChemistryJilin UniversityChangchunPeople’s Republic of China
  2. 2.Norman Bethune First Hospital, Jilin UniversityChangchunPeople’s Republic of China

Personalised recommendations