Skip to main content

Advertisement

SpringerLink
Log in

Preparation and Characterization of Cisplatin Magnetic Solid Lipid Nanoparticles (MSLNs): Effects of Loading Procedures of Fe3O4 Nanoparticles

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

ABSTRACT

Purpose

In order to improve formulation of targeting chemotherapy, cisplatin-loaded magnetic solid lipid nanoparticles (MSLNs) were prepared. In present study, the deliberate loading of Fe3O4 magnetic nanoparticles (MNs) into cisplatin SLNs was developed.

Methods

SLNs were produced by film scattering ultrasonic technique. The effects of two different loading procedures of MNs on the microstructure and physicochemical properties of MSLNs were investigated by transmission electron microscopy (TEM), zetasizer, infrared spectroscopy (IR), and fluorescence spectroscopy. In vitro drug release and cytotoxicity against human cervical carcinoma SiHa cells, in vivo tumor cell uptake and target tissue distribution of MSLNs under external magnetic field were investigated.

Results

The encapsulation efficiency of cisplatin and the content of MNs in procedure I SLNs were 69.20 ± 4.5% and 2.16 ± 0.53 mg/mL, respectively, which were higher than those of procedure II MSLNs. In procedure I, the MNs, which were combined with lipids during film formation, distributed in the middle of the lipid layer in SLNs. Differently, in procedure II, the MNs and cisplatin were contained in an interior compartment in SLNs, resulting from mixing with drugs during hydration of lipid film. The procedure I MSLNs had higher cytotoxicity than procedure II MSLNs or free cisplatin. With in vivo intratumoral administration, cisplatin concentration in the tumor tissue was maintained at higher level for MSLNs than that for free cisplatin, especially under external magnetic field.

Conclusions

Procedure I, the developed deliberate MNs loading method, was superior over procedure II in cisplatin encapsulation efficiency, MNs content and cell cytotoxicity.

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

Similar content being viewed by others

Abbreviations

AAS:

Graphite furnace atomic absorption spectrometer

DMSO:

Dimethyl sulfoxide

EE:

Encapsulation efficiency

F-68:

Poloxamer 188

FBS:

Fetal bovine serum

FT-IR:

Fourier transform infrared spectroscopy

GMS:

Glycerol monostearate

HSPC:

Hydrogenated soybean lecithin

MNs:

Magnetic nanoparticles

MSLNs:

Magnetic solid lipid nanoparticles

MTT:

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide

PBS:

Phosphate-buffered saline

PDI:

Polydispersity index

SLNs:

Solid lipid nanoparticles

TEM:

Transmission electron microscopy

REFERENCES

  1. Ali BH, Al-Moundhri MS. Agents ameliorating or augmenting the nephro-toxicity of cisplatin and other platinum compounds: a review of somerecent research. Food Chem Toxicol. 2006;44(8):1173–83.

    Article  CAS  PubMed  Google Scholar 

  2. Marchion DC, Xiong Y, Chen N, Bicaku E, Stickles XB, et al. The BCL2 antagonist of cell death pathway influences endometrial cancer cell sensitivity to cisplatin. Gynecol Oncol. 2012;124(1):119–24.

    Article  PubMed  Google Scholar 

  3. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring muta-tions of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11:121–8.

    Article  CAS  PubMed  Google Scholar 

  4. Kuang Y, Liu J, Liu ZL, Zhuo RX. Cholesterol based anionic long-circulating cisplatin liposomes with reduced renal toxicity. Biomaterials. 2012;33(5):1596–56.

    Article  CAS  PubMed  Google Scholar 

  5. Qu J, Li X, Wang J, Mi WJ, Xie KL, Qiu JH. Inhalation of hydrogen gas attenuates cisplatin-induced ototoxicity via reducing oxidative stress. Int J Pediatr Otorhinolaryngol. 2012;76(1):111–5.

    Article  PubMed  Google Scholar 

  6. Li H, Zhao X, Ma Y, Zhai G, Li L, Lou H. Enhancement of gastrointestinal absorption of quercitin by solid lipid nanoparticles. J Control Release. 2009;133(3):238–44.

    Article  CAS  PubMed  Google Scholar 

  7. Ying XY, Cui D, Yu L, Du YZ. Solid lipid nanoparticles modified with chitosan oligosaccharides for the controlled release of doxorubicin. Carbohydr Polym. 2011;84(4):1357–64.

    Article  CAS  Google Scholar 

  8. Santander-Ortega MJ, Lozano-Lopez MV, Bastos-Gonzalez D, Peula-Garcia JM, Ortega-Vinuesa JL. Novel core-shell lipid chitosan and lipid-poloxamer nanocapsules: stability by hydration forces. Colloid Polym Sci. 2010;288(2):159–72.

    Article  CAS  Google Scholar 

  9. Wu LF, Tang C, Yin CH. Folate-mediated solid–liquid lipid nanoparticles for paclitaxel-coated poly (ethylene glycol). Drug Dev Ind Pharm. 2010;36(4):439–48.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang WL, Liu JP, Li SC, Chen MY, Liu H. Preparation and evaluation of stealth tashinone IIA-loaded solid lipid nanoparticles: influence of Poloxamer 188 coating on phagocytic uptake. J Microencapsul. 2008;25(3):203–9.

    Article  CAS  PubMed  Google Scholar 

  11. Nobuto H, Sugita T, Kubo T, Shimose S, Yasunaga Y, Murakami T, et al. Evaluation of systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet. Int J Cancer. 2004;109(4):627–35.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang JQ, Zhang ZR, Yang H, Tan QY, Qin SR, Qiu XL. Lyophilized paclitaxel magnetoliposomes as a potential drug delivery system for breast carcinoma via parenteral administration: in vitro and in vivo studies. Pharm Res. 2005;22(4):573–83.

    Article  CAS  PubMed  Google Scholar 

  13. Cavalli R, Caputo O, Gasco MR. Solid lipospheres of doxorubicin and idarubicin. Int J Pharm. 1993;89(1):9–12.

    Article  Google Scholar 

  14. Miglietta A, Cavallib R, Boccaa C, Bocca C, Gabriel L, Gasco MR. Cellular uptake and cytotoxicity of solid lipid nanospheres (SLN) incorporating doxorubicin or paclitaxel. Int J Pharm. 2000;210(1–2):61–7.

    Article  CAS  PubMed  Google Scholar 

  15. Uagio E, Cavalli R, Gasco MR. Incorporation of cyclosporin A in solid lipid nanoparticles (SLN). Int J Pharm. 2002;241(2):341–4.

    Article  Google Scholar 

  16. Westesen K, Siekmann B. Investigation of the gel formation of phospholipid-stabilized solid lipid nanoparticles. Int J Pharm. 1997;151(1):35–45.

    Article  CAS  Google Scholar 

  17. Zhao S, Yang CQ, Yan JW, Wang J. A novel solvethermal method for the preparation of magnetic monodisperse Fe3O4 nanoparticles II: High-surface-activity ferrihydrite used as precursor. Mater Res Bull. 2013;48(10):4385–9.

    Article  CAS  Google Scholar 

  18. Manjunath K, Venkateswarlu V. Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration. J Control Release. 2005;107(2):215–28.

    Article  CAS  PubMed  Google Scholar 

  19. Liu SL, Zhang LN, Zhou JP, Wu RX. Structure and properties of cellulose/Fe2O3nanocomposite fibers spun via an effective pathway. J Phys Chem C. 2008;112(12):4538–44.

    Article  CAS  Google Scholar 

  20. Wang L, Yang CQ, Wang J. Effects of loading procedures of magnetic nanoparticles on the structure and physicochemical properties of cisplatin magnetic liposomes. J Microencapsul. 2012;29(8):781–9.

    Article  CAS  PubMed  Google Scholar 

  21. Jenning V, Mäder K, Gohla SH. Solid Lipid Nanoparticles (SLN) based on binary mixtures of liquid and solid lipids: a (1)H-NMR study. Int J Pharm. 2000;205(1–2):15–21.

    Article  CAS  PubMed  Google Scholar 

  22. García-Fuentes M, Torres D, Alonso MJ. Design of lipid nanoparticles for the oral delivery of hydrophilic macromolecules. Colloid Surf B. 2002;27(2–3):159–68.

    Google Scholar 

  23. Mehnert W, Mäder K. Solid lipid nanoparticles-production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2–3):165–96.

    Article  CAS  PubMed  Google Scholar 

  24. Schwarz C, Mehnert W, Lucks JS, Miiller RH. Solid Lipid Nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization. J Control Release. 1994;30:83–96.

    Article  CAS  Google Scholar 

  25. Bloch K, Bangham AD, Scherphof GL, Kennedy EP, Waite M, Hostetler KY. Lipids and mombranes: past. Presint and future. Amsterdam: Elsever; 1986. p. 336.

    Google Scholar 

  26. Wang W, Li LM, Li ZL, Xi SG. The molecular mechanisms of interaction between rare earth irons and DPPC liposome. Spectrosc Spectr Anal. 1993;13(5):51–4.

    Google Scholar 

  27. Neumann MG, Schmitt CC, Iamazaki ET. A Fuorescence study of the interactions between sodium alginate and surfactants. Permissions Repr. 2003;338(10):1109–13.

    CAS  Google Scholar 

  28. Thakkar VT, Shah PA, Soni TG, Parmar MY, Gohel MC, Gandhi TR. Goodness-of-fit model-dependent approach for release kinetics of levofloxacin hemihydrates floating tablet. Dissolut Technol. 2009;16(1):35–9.

    CAS  Google Scholar 

  29. Yokoyama M, Okano T, Sakurai Y, Suwa S, Kataoka K. Introduction of cisplatin into polymeric micelle. J Control Rel. 1996;39:351–6.

    Article  CAS  Google Scholar 

  30. Hwang TL, Lee WR, Hua SC, Fang JY. Cisplatin encapsulated in phosphatidylethanolamine liposomes enhances the in vitro cytotoxicity and in vivo intratumor drug accumulation against melanomas. J Dermatol Sci. 2007;46:11–20.

    Article  CAS  PubMed  Google Scholar 

  31. Vasir JK, Reddy MK, Labhasetwar VD. Nanosystems in drug targeting: opportunities and challenges. Curr Nanosci. 2005;1(1):47–64.

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS AND DISCLOSURES

The financial support for this work by the Hebei Provincial Natural Science Fund of China (H2013206040, 2008001072) is greatly acknowledged.

Author information

Authors and Affiliations

  1. School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China

    Sha Zhao, Yongle Zhang, Yazhu Han & Jing Wang

  2. Preparation of the Third Hospital, Hebei Medical University, Shijiazhuang, 050051, China

    Jie Yang

Authors
  1. Sha Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongle Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yazhu Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jie Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jing Wang or Jie Yang.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 138 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, S., Zhang, Y., Han, Y. et al. Preparation and Characterization of Cisplatin Magnetic Solid Lipid Nanoparticles (MSLNs): Effects of Loading Procedures of Fe3O4 Nanoparticles. Pharm Res 32, 482–491 (2015). https://doi.org/10.1007/s11095-014-1476-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-014-1476-2

KEY WORDS

Search

Navigation