Skip to main content
Log in

Assembling drug-loaded-layered double hydroxide nanohybrids with poloxamer 188 for improved cellular uptake and in vitro efficacy

  • Article
  • Published:
Journal of Materials Research Aims and scope Submit manuscript

Abstract

Layered Double Hydroxide (LDHs) requires surface functionalization to achieve desirable colloidal and biological stability for effective drug delivery. The present work reported a new functionalized approaches to construct drug-loaded nanohybrids (2:1E and 2.8:1E) by co-assembling LDH sheets, penta-fluorouracil (5Fu) and poloxamer 188 through exfoliation reassembling. Some analysis showed that more poloxamer 188 were needed to prepare 2:1E with appropriate particle size than 2.8:1E. Besides, 2.8:1E shows advantages in drug loading rate and dispersion as compared with ion exchange method. In addition, these nanohybrids can improve the sudden release of 5Fu in naked drug-loaded LDH. Most importantly, significant enhanced cell uptake and better cytotoxicity were seen in these nanohybrids in contrast to naked drug-loaded LDH. Lastly, the results reveal that assembling drug-loaded LDH with poloxamer 188 is a promising strategy to improve cellular uptake and in vitro efficacy of LDHs for biomedical applications.

Graphical abstract

Drug-loaded nanohybrids were synthesised by co-assembling LDH sheets, penta-fluorouracil (5Fu) and poloxamer 188 through exfoliation reassembling, and showed advantages in dispersion, enhanced cell uptake and better cytotoxicity as compared with naked drug-loaded-LDH prepared by ion exchange method.

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

Access this article

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

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

Data availability

We declare that all data generated or analyzed during this study are included in this published article; and the data are available from the corresponding author on reasonable request.

References

  1. X. Yang, L. Wang, S. Guo, R. Li, F. Tian, S. Guan, S. Zhou, J. Lu, Self-cycling free radical generator from LDH-based nanohybrids for ferroptosis-enhanced chemodynamic therapy. Adv. Healthcare Mater. 10(18), 2100539 (2021). https://doi.org/10.1002/adhm.202100539

    Article  CAS  Google Scholar 

  2. J. Lu, Z. Guo, S. Che, F. Gao, Z. Gu, J. Xu, Y. Chi, W. Xu, J. Zhang, N. Takuya, J. Yu, L. Zhao, Dihydroartemisinin loaded layered double hydroxide nanocomposites for tumor specific photothermal–chemodynamic therapy. J. Mater. Chem. B 8, 11082 (2020). https://doi.org/10.1039/D0TB01964J

    Article  CAS  Google Scholar 

  3. B. Li, J. Tang, W. Chen, G. Hao, K. Nyoman, G. Zi, Z.P. Xu, Novel theranostic nanoplatform for complete mice tumor elimination via MR-imaging-guided acid-enhanced photothermo-/chemo-therapy. Biomaterials 177, 40 (2018). https://doi.org/10.1016/j.biomaterials.2018.05.055

    Article  CAS  Google Scholar 

  4. H. Zuo, W. Chen, H.M. Cooper, Z.P. Xu, A facile way of modifying layered double hydroxide nanoparticles with targeting ligand-conjugated albumin for enhanced delivery to brain tumour cells. ACS Appl. Mater. Inter. 9, 20444 (2017). https://doi.org/10.1021/acsami.7b06421

    Article  CAS  Google Scholar 

  5. J. Li, B. Li, J. Wang, L. He, Y. Zhao, Recent advances in layered double hydroxides and their derivatives for biomedical applications. Acta Chim. Sinica 79, 238 (2021). https://doi.org/10.6023/A20090441

    Article  CAS  Google Scholar 

  6. C. Vasti, D.A. Bedoya, R. Rojas, C. Giacomelli, Effect of the protein corona on the colloidal stability and reactivity of LDH based nanocarriers. J. Mater. Chem. B 4(11), 2008 (2016). https://doi.org/10.1039/C5TB02698A

    Article  CAS  Google Scholar 

  7. M. Yan, C. Yang, B. Huang, Z. Huang, L. Huang, X. Zhang, C. Zhao, Systemic toxicity induced by aggregated layered double hydroxide nanoparticles. Int. J. Nanomed. 12, 7183 (2017). https://doi.org/10.2147/ijn.s146414

    Article  CAS  Google Scholar 

  8. Y.M. Kuo, Y. Kuthati, R.K. Kankala, P.R. Wei, C.F. Weng, C.L. Liu, P.J. Sung, C.Y. Mouc, C.H. Lee, Layered double hydroxide nanoparticles to enhance organ-specific targeting and the anti-proliferative effect of cisplatin. J. Mater. Chem. B 3(17), 3447 (2015). https://doi.org/10.1039/C4TB01989J

    Article  CAS  Google Scholar 

  9. M. Pavlovic, L. Li, F. Dits, Z. Gu, M. Adok-Sipiczki, I. Szilágyi, Aggregation of layered double hydroxide nanoparticles in the presence of heparin: towards highly stable delivery systems. RSC Adv. 6(20), 16159 (2016). https://doi.org/10.1039/C5RA26072H

    Article  CAS  Google Scholar 

  10. Z. Gu, H. Zuo, L. Li, A. Wu, Z.P. Xu, Pre-coating layered double hydroxide nanoparticles with albumin to improve colloidal stability and cellular uptake. J Mater. Chem. B 3(16), 3331 (2015). https://doi.org/10.1039/C5TB00248F

    Article  CAS  Google Scholar 

  11. S. Senapati, R. Shukla, Y.B. Tripathi, A.K. Mahanta, D. Rana, P. Maiti, Engineered cellular uptake and controlled drug delivery using two dimensional nanoparticle and polymer for cancer treatment. Mol. Pharm. 15, 679 (2018). https://doi.org/10.1021/acs.molpharmaceut.7b01119

    Article  CAS  Google Scholar 

  12. T. Xu, J. Zhang, H. Chi, F. Cao, Multifunctional properties of organic-inorganic hybrid nanocomposites based on chitosan derivatives and layered double hydroxides for ocular drug delivery. Acta Biomater. 36, 152 (2016). https://doi.org/10.1016/j.actbio.2016.02.041

    Article  CAS  Google Scholar 

  13. Y.F. Zhang, X.W. Wu, Y.W. Mi, H.P. Li, W.G. Hou, Engineering of (10-hydroxycamptothecin intercalated layered double hydroxide) @liposome nanocomposites with excellent water dispersity. J. Phys. Chem. Solids 108, 125 (2017). https://doi.org/10.1016/j.jpcs.2017.04.018

    Article  CAS  Google Scholar 

  14. A.J. Dong, X. Li, W.W. Wang, S.C. Hang, J.F. Liu, J.J. Liu, J.Q. Zhao, S.X. Xu, L.D. Deng, Layered double hydroxide modified by PEGylated hyaluronic acid as a hybrid nanocarrier for targeted drug delivery. Trans. Tianjin Univ. 22(3), 237 (2016). https://doi.org/10.1007/s12209-016-2710-2

    Article  CAS  Google Scholar 

  15. X. Wang, D. Sun, S. Liu, R. Wang, The effect of block copolymer EPE1100 on the colloidal stability of Mg–Al LDH dispersions. J. Colloid Interf. Sci. 289(2), 410 (2005). https://doi.org/10.1016/j.jcis.2005.04.001

    Article  CAS  Google Scholar 

  16. S.R. Croy, G.S. Kwon, Polymeric micelles for drug delivery. Curr. Pharm. Des. 12(36), 4669 (2006)

    Article  CAS  Google Scholar 

  17. E.V. Batrakova, L. Shu, A.M. Brynskikh, A.K. Sharma, Y. Li, M. Boska, G. Nan, R.L. Mosley, V.Y. Alakhov, H.E. Gendelman, A.V. Kabanov, Effects of pluronic and doxorubicin on drug uptake, cellular metabolism, apoptosis and tumor inhibition in animal models of MDR cancers. J Control. Release 143(3), 290 (2010). https://doi.org/10.1016/j.jconrel.2010.01.004

    Article  CAS  Google Scholar 

  18. X. Lu, L. Meng, H. Li, D. Na, R. Zhang, W. Hou, Facile fabrication of ibuprofen–LDH nanohybrids via a delamination/reassembling process. Mater. Res. Bull. 48(4), 1512 (2013). https://doi.org/10.1016/j.materresbull.2012.12.057

    Article  CAS  Google Scholar 

  19. X. Wu, H. Li, S. Song, R. Zhang, W. Hou, Facile synthesis of camptothecin intercalated layered double hydroxide nanohybrids via a coassembly route. Int. J. Pharmaceut. 454(1), 453 (2013). https://doi.org/10.1016/j.ijpharm.2013.06.043

    Article  CAS  Google Scholar 

  20. J.M. Oh, S.J. Choi, G.E. Lee, S.H. Han, J.H. Choy, Inorganic drug-delivery nanovehicle conjugated with cancer-cell-specific ligand. Adv. Funct. Mater. 19, 1617 (2009). https://doi.org/10.1002/adfm.200801127

    Article  CAS  Google Scholar 

  21. Y. Zou, X. Wang, Y. Ai, Y. Liu, J. Li, Y. Ji, X. Wang, Coagulation behavior of graphene oxide on nanocrystallined Mg/Al layered double hydroxides: batch experimental and theoretical calculation study. Environ. Sci. Technol. 50, 3658 (2016). https://doi.org/10.1021/acs.est.6b00255

    Article  CAS  Google Scholar 

  22. J. Wang, W. Zhang, L. Hao, J. Sun, F. Yuan, Amino acid–intercalated layered double hydroxide core @ ordered porous silica shell as drug carriers: design and applications. J. Mater. Res. 34(22), 1 (2019). https://doi.org/10.1557/jmr.2019.324

    Article  CAS  Google Scholar 

  23. F. Bellezza, A. Alberani, M. Nocchetti, V. Marsili, A. Cipiciani, Intercalation of 5-fluorouracil into ZnAl hydrotalcite-like nanoparticles: preparation, characterization and drug release. Appl. Clay Sci. 101, 320 (2014)

    Article  CAS  Google Scholar 

  24. Z.B. Cao, N.N.M. Adnan, G.Y. Wang, A. Rawal, B.Y. Shi, R.Z. Liu, K. Liang, L.Y. Zhao, J.J. Gooding, C. Boyer, Enhanced colloidal stability and protein resistance of layered double hydroxide nanoparticles with phosphonic acid-terminated PEG coating for drug delivery. J. Colloid Interface Sci. 521, 242 (2018). https://doi.org/10.1016/j.jcis.2018.03.006

    Article  CAS  Google Scholar 

  25. Y.P. Zhang, H.P. Li, N. Du, S. Song, W.G. Hou, Betamethasone dipropionate intercalated layered double hydroxide and the composite with liposome for improved water dispersity. Appl. Clay Sci. 143, 336 (2017). https://doi.org/10.1016/j.clay.2017.04.001

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank to the National Natural Science Foundation of China [81860631, 21967013, 21867013], Scientific Research Fund of Jiangxi Provincial Health Commission [20201118], and Natural Science Foundation of Jiangxi Province (20192ACBL20032).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jin Ren, Liang Liang or Jingmou Yu.

Ethics declarations

Conflict of interest

Authors declare that there are no conflicts of interest on the present study.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 344 KB).

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ren, J., Liang, L., Yang, Y. et al. Assembling drug-loaded-layered double hydroxide nanohybrids with poloxamer 188 for improved cellular uptake and in vitro efficacy. Journal of Materials Research 38, 337–349 (2023). https://doi.org/10.1557/s43578-022-00813-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1557/s43578-022-00813-w

Keywords

Navigation