Skip to main content
SpringerLink
Log in

NiCu-silica nanoparticles as a potential drug delivery system

  • Review Paper: Sol–gel and hybrid materials for biological and health (medical) applications
  • Published:
Journal of Sol-Gel Science and Technology Aims and scope Submit manuscript

Abstract

Many groups have already investigated the use of NiCu magnetic nanoparticles (MNPs) as mediators for magnetic fluid hyperthermia, but we were the first to report the potential of NiCu MNPs as bimodal therapeutic systems, capable of simultaneous magnetic hyperthermia (MH) and targeted drug delivery. The superparamagnetic nanoparticles have a magnetic core, which enables their manipulation through an external magnetic field, a biocompatible layer, providing a surface for attachment of suitable receptors for targeting specific tissues, and a therapeutic load either incorporated inside the coating pores or hosted within internal cavities of the particles. In this study, we incorporated three model drugs with different pharmacological activity into superparamagnetic NixCu1−x nanoparticles. The superparamagnetic NixCu1−x nanoparticles were prepared using a sol–gel method, and exhibited a Curie temperature (TC) in the therapeutic range for use in MH. The nanoparticles were prepared in a silica matrix to avoid their agglomeration during thermal treatment and to provide suitable compartments for incorporation inside the pores. The release of the incorporated drugs paracetamol, bupivacaine hydrochloride, and pentoxifylline was studied using an in vitro release system, where UV–visible spectrophotometry (UV/Vis) was used for quantification of the released drug. The NixCu1−x nanoparticles were characterized using X-ray diffraction analysis, thermogravimetric analysis (TGA/SDTA), Fourier transform infrared spectroscopy, scanning electron microscopy, and magnetic measurements. Surface area and pore size were determined by using BET analysis. Finally, the biocompatibility of the samples was tested on human skin-derived fibroblasts.

Highlights

  • NiCu MNPs are often functionalized to improve their potential for biomedicine.

  • NiCu magnetic nanoparticles are very promising for multimodal cancer therapies through combination of magnetic hyperthermia and controlled drug delivery.

  • Controlled drug delivery systems have several advantages compared with traditional pharmaceutical formulations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Tartaj P, Morales MdP, Veintemillas-Verdaguer S, González-Carreño T, Carlos JS (2003) The preparation of magnetic nanoparticles for applications in biomedicine. J Phys D: Appl Phys 36:R182

    CAS  Google Scholar 

  2. Dobson QAP, Connolly J, Jones SK (2003) Applications of magnetic nanoparticles in biomedicine. J Phys D: Appl Phys 36:R167

    Google Scholar 

  3. Tartaj P, Morales MP, González-Carreño T, Veintemillas-Verdaguer S, Serna CJ (2005) Advances in magnetic nanoparticles for biotechnology applications. J Magn Magn Mater 290–291:28–34. Part 1

    Google Scholar 

  4. Ban I, Stergar J, Maver U (2018) NiCu magnetic nanoparticles: review of synthesis methods, surface functionalization approaches, and biomedical applications. Nanotechnol Rev 7:187

  5. Cihoric N, Tsikkinis A, van Rhoon G, Crezee H, Aebersold DM, Bodis S, Beck M, Nadobny J, Budach V, Wust P, Ghadjar P (2015) Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry. Int J Hyperth 31:609–614

    CAS  Google Scholar 

  6. Dobson J (2006) Magnetic nanoparticles for drug delivery. Drug Dev Res 67:55–60

    CAS  Google Scholar 

  7. Sun C, Lee JS, Zhang M (2008) Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliv Rev 60:1252–1265

    CAS  Google Scholar 

  8. Chomoucka J, Drbohlavova J, Huska D, Adam V, Kizek R, Hubalek J (2010) Magnetic nanoparticles and targeted drug delivering. Pharmacol Res 62:144–149

    CAS  Google Scholar 

  9. Arruebo M, Fernández-Pacheco R, Ibarra MR, Santamaría J (2007) Magnetic nanoparticles for drug delivery. Nano Today 2:22–32

    Google Scholar 

  10. McBain SC, Yiu HHP, Dobson J (2008) Magnetic nanoparticles for gene and drug delivery. Int J Nanomed 3:169–180

    CAS  Google Scholar 

  11. Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H (2012) Nanoparticles as drug delivery systems. Pharmacol Rep 64:1020–1037

    CAS  Google Scholar 

  12. Ferk G, Stergar J, Makovec D, Hamler A, Jagličić Z, Drofenik M, Ban I (2015) Synthesis and characterization of Ni–Cu alloy nanoparticles with a tunable Curie temperature. J Alloy Compd 648:53–58

    CAS  Google Scholar 

  13. Bajpai AK, Gupta R (2011) Magnetically mediated release of ciprofloxacin from polyvinyl alcohol based superparamagnetic nanocomposites. J Mater Sci Mater Med 22:357–369

    CAS  Google Scholar 

  14. Munnier E, Cohen-Jonathan S, Linassier C, Douziech-Eyrolles L, Marchais H, Souce M, Herve K, Dubois P, Chourpa I (2008) Novel method of doxorubicin-SPION reversible association for magnetic drug targeting. Int J Pharm 363:170–176

    CAS  Google Scholar 

  15. Alexiou C, Arnold W, Klein RJ, Parak FG, Hulin P, Bergemann C, Erhardt W, Wagenpfeil S, Lubbe AS (2000) Locoregional cancer treatment with magnetic drug targeting. Cancer Res 60:6641–6648

    CAS  Google Scholar 

  16. Lubbe AS, Bergemann C, Riess H, Schriever F, Reichardt P, Possinger K, Matthias M, Dorken B, Herrmann F, Gurtler R, Hohenberger P, Haas N, Sohr R, Sander B, Lemke AJ, Ohlendorf D, Huhnt W, Huhn D (1996) Clinical experiences with magnetic drug targeting: a phase I study with 4′-epidoxorubicin in 14 patients with advanced solid tumors. Cancer Res 56:4686–4693

    CAS  Google Scholar 

  17. Kayal S, Ramanujan RV (2010) Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery. Mater Sci Eng: C 30:484–490

    CAS  Google Scholar 

  18. Hałupka-Bryl M, Bednarowicz M, Dobosz B, Krzyminiewski R, Zalewski T, Wereszczyńska B, Nowaczyk G, Jarek M, Nagasaki Y (2015) Doxorubicin loaded PEG-b-poly(4-vinylbenzylphosphonate) coated magnetic iron oxide nanoparticles for targeted drug delivery. J Magn Magn Mater 384:320–327

    Google Scholar 

  19. Oka C, Ushimaru K, Horiishi N, Tsuge T, Kitamoto Y (2015) Core–shell composite particles composed of biodegradable polymer particles and magnetic iron oxide nanoparticles for targeted drug delivery. J Magn Magn Mater 381:278–284

    CAS  Google Scholar 

  20. Araújo-Barbosa S, Morales MA (2019) Nanoparticles of Ni1−xCux alloys for enhanced heating in magnetic hyperthermia. J Alloy Compd 787:935–943

    Google Scholar 

  21. Amrollahi P, Ataie A, Nozari A, Seyedjafari E, Shafiee A (2015) Cytotoxicity evaluation and magnetic characteristics of mechano-thermally synthesized CuNi nanoparticles for hyperthermia. J Mater Eng Perform 24:1220–1225

    CAS  Google Scholar 

  22. Ban I, Stergar J, Drofenik M, Ferk G, Makovec D (2011) Synthesis of copper–nickel nanoparticles prepared by mechanical milling for use in magnetic hyperthermia. J Magn Magn Mater 323:2254–2258

    CAS  Google Scholar 

  23. Ferk G, Stergar J, Drofenik M, Makovec D, Hamler A, Jagličić Z, Ban I (2014) The synthesis and characterization of nickel–copper alloy nanoparticles with a narrow size distribution using sol–gel synthesis. Mater Lett 124:39–42

    CAS  Google Scholar 

  24. Stergar J, Ferk G, Ban I, Drofenik M, Hamler A, Jagodič M, Makovec D (2013) The synthesis and characterization of copper–nickel alloy nanoparticles with a therapeutic Curie point using the microemulsion method. J Alloy Compd 576:220–226

    CAS  Google Scholar 

  25. Chatterjee J, Bettge M, Haik Y, Chen CJen (2005) Synthesis and characterization of polymer encapsulated Cu–Ni magnetic nanoparticles for hyperthermia applications. J Magn Magn Mater 293:303–309

    CAS  Google Scholar 

  26. Paulus JA, Parida GR, Tucker RD, Park JB (1997) Corrosion analysis of NiCu and PdCo thermal seed alloys used as interstitial hyperthermia implants. Biomaterials 18:1609–1614

    CAS  Google Scholar 

  27. Bettge M, Chatterjee J, Haik Y (2004) Physically synthesized Ni-Cu nanoparticles for magnetic hyperthermia. Biomagn Res Technol 2:4–4

    Google Scholar 

  28. Ahmed J, Ramanujachary KV, Lofland SE, Furiato A, Gupta G, Shivaprasad SM, Ganguli AK (2008) Bimetallic Cu–Ni nanoparticles of varying composition (CuNi3, CuNi, Cu3Ni). Colloids Surf A: Physicochemical Eng Asp 331:206–212

    CAS  Google Scholar 

  29. Feng J, Zhang C-P (2006) Preparation of Cu–Ni alloy nanocrystallites in water-in-oil microemulsions. J Colloid Interface Sci 293:414–420

    CAS  Google Scholar 

  30. Songping W, Jing N, Li J, Zhenou Z (2007) Preparation of ultra-fine copper–nickel bimetallic powders with hydrothermal–reduction method. Mater Chem Phys 105:71–75

    Google Scholar 

  31. Mohamed Saeed GH, Radiman S, Gasaymeh SS, Lim HN, Huang NM (2010) Mild hydrothermal synthesis of Ni–Cu nanoparticles. J Nanomater 2010:5

    Google Scholar 

  32. Foyet A, Hauser A, Schäfer W (2007) Double template electrochemical deposition and characterization of NiCo and NiCu alloys nanoparticles and nanofilms. J Solid State Electrochem 12:47–55

    Google Scholar 

  33. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF (2013) The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology 21:201–232

    CAS  Google Scholar 

  34. Bardsley H, Gristwood R, Baker H, Watson N, Nimmo W (1998) A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 46:245–249

    CAS  Google Scholar 

  35. Schonharting MM, Schade UF (1989) The effect of pentoxifylline in septic shock-new pharmacologic aspects of an established drug. J Med 20:97–105

    CAS  Google Scholar 

  36. Dobson QAPaJCaSKJaJ (2003) Applications of magnetic nanoparticles in biomedicine. J Phys D: Appl Phys 36:R167

    Google Scholar 

  37. Gupta AK, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26:3995–4021

    CAS  Google Scholar 

  38. Issa B, Obaidat IM, Albiss BA, Haik Y (2013) Magnetic nanoparticles: surface effects and properties related to biomedicine applications. Int J Mol Sci 14:21266–21305

    CAS  Google Scholar 

  39. Stergar J, Ban I, Gradišnik L, Maver U (2018) Novel drug delivery system based on NiCu nanoparticles for targeting various cells. J Sol–Gel Sci Technol 88:57–65

    CAS  Google Scholar 

  40. Maver U, Xhanari K, Zizek M, Korte D, Gradisnik L, Franko M, Finsgar M (2018) A combination of interdisciplinary analytical tools for evaluation of multi-layered coatings on medical grade stainless steel for biomedical applications. Eur J Pharm Biopharm 128:230–246

    CAS  Google Scholar 

  41. Milojević M, Gradišnik L, Stergar J, Skelin Klemen M, Stožer A, Vesenjak M, Dobnik Dubrovski P, Maver T, Mohan T, Stana Kleinschek K, Maver U (2019) Development of multifunctional 3D printed bioscaffolds from polysaccharides and NiCu nanoparticles and their application. Appl Surf Sci 488:836–852

    Google Scholar 

  42. Sykuła-Zając A, Łodyga-Chruścińska E, Pałecz B, Dinnebier RE, Griesser UJ, Niederwanger V (2011) Thermal and X-ray analysis of racemic bupivacaine hydrochloride. J Therm Anal Calorim 105:1031–1036

    Google Scholar 

  43. Bavnhøj CG, Knopp MM, Madsen CM, Löbmann K (2019) The role interplay between mesoporous silica pore volume and surface area and their effect on drug loading capacity. Int J Pharm: X 1:100008

    Google Scholar 

  44. Refat MS, Mohamed GG, El-Sayed MY, Killa HMA, Fetooh H (2017) Spectroscopic and thermal degradation behavior of Mg(II), Ca(II), Ba(II) and Sr(II) complexes with paracetamol drug. Arab J Chem 10:S2376–S2387

    CAS  Google Scholar 

  45. Martins ML, Eckert J, Jacobsen H, dos Santos EC, Ignazzi R, de Araujo DR, Bellissent-Funel M-C, Natali F, Marek Koza M, Matic A, de Paula E, Bordallo HN (2017) Raman and Infrared spectroscopies and X-ray diffraction data on bupivacaine and ropivacaine complexed with 2-hydroxypropyl−β−cyclodextrin. Data Brief 15:25–29

    Google Scholar 

  46. Rahim SA, Carter PA, Elkordy AA (2015) Design and evaluation of effervescent floating tablets based on hydroxyethyl cellulose and sodium alginate using pentoxifylline as a model drug. Drug Des Dev Ther 9:1843–1857

    Google Scholar 

  47. Maver U, Godec A, Bele M, Planinšek O, Gaberšček M, Srčič S, Jamnik J (2007) Novel hybrid silica xerogels for stabilization and controlled release of drug. Int J Pharmaceutics 330:164–174

    CAS  Google Scholar 

  48. Godec A, Maver U, Bele M, Planinsek O, Srcic S, Gaberscek M, Jamnik J (2007) Vitrification from solution in restricted space: formation and stabilization of amorphous nifedipine in a nanoporous silica xerogel carrier. Int J Pharm 343:131–140

    CAS  Google Scholar 

  49. Maver U, Žnidaršič A, Saboti D, Srčič S, Gaberšček M, Godec A, Planinšek O (2010) The relation between the interfacial contact and SiO2 coating efficiency and properties in the case of two clarithromycin polymorphs. Colloids Surf A: Physicochem Eng Asp 371:119–125

    CAS  Google Scholar 

  50. Ukmar T, Maver U, Planinšek O, Pintar A, Kaučič V, Godec A, Gaberšček M (2012) Guest–host van der Waals interactions decisively affect the molecular transport in mesoporous media. J Mater Chem 22:1112–1120

    CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the financial support for this project received from the Slovenian Research Agency (grant numbers: P2-0006, P3-0036, and J1-9169).

Author information

Authors and Affiliations

  1. Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova ulica 17, SI-2000, Maribor, Slovenia

    Janja Stergar, Matjaž Kristl & Irena Ban

  2. Faculty of Medicine, Institute of Biomedical Sciences, University of Maribor, Taborska ulica 8, SI-2000, Maribor, Slovenia

    Janja Stergar, Uroš Maver & Lidija Gradišnik

  3. Department of Materials Chemistry, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia

    Marjan Bele

Authors
  1. Janja Stergar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Uroš Maver
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marjan Bele
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lidija Gradišnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matjaž Kristl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irena Ban
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Janja Stergar or Uroš Maver.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stergar, J., Maver, U., Bele, M. et al. NiCu-silica nanoparticles as a potential drug delivery system. J Sol-Gel Sci Technol 101, 493–504 (2022). https://doi.org/10.1007/s10971-020-05280-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10971-020-05280-5

Keywords

Search

Navigation