Skip to main content
SpringerLink
Log in

Quantitative lipid composition characterization of intact liposomes via 31P nuclear magnetic resonance spectroscopy

  • Special Issue: Original Paper
  • Novel Analytical Technologies Contributing to Clinical and Pharmaceutical Research Fields
  • Published:
Analytical Sciences Aims and scope Submit manuscript

Abstract

Drug delivery systems (DDS) are important methods to maximize drug efficacy by enabling in vivo accumulation at the target site. Liposomes, which are nanoscale vesicles consisting of lipid bilayers, are widely used for clinical DDS. The lipid composition of an intact liposome is a significant factor that directly affects its characteristics and functions. Thus, it is important to develop quantitative or qualitative analytical methods to characterize the lipid composition. Nuclear magnetic resonance (NMR) of phosphorus (31P) is a particularly sensitive and non-destructive approach because phospholipid components have one 31P nucleus per molecule. Here, we demonstrate quantitative observations of individual phospholipids in intact liposomes via solution 31P-NMR. In addition, the 31P linewidths became narrower if the liposomes contained > 10 mol% of polyethylene glycol-(PEGylated) phospholipids, which also contributed to liposome down-sizing. Down-sizing and PEGylation are important strategies for efficient drug delivery. Hence, 31P-NMR can be used to analyze phospholipids in liposomes and related pharmaceutical preparations for quality control.

Graphical abstract

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

Similar content being viewed by others

Data availability

All data collected and analyzed in this research are available within this published article.

References

  1. T.C. Ezike et al., Advances in drug delivery systems, challenges and future directions. Heliyon 9, e17488 (2023)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. G. Bozzuto, A. Molinari, Liposomes as nanomedical devices. Int. J. Nanomed. 10, 975–999 (2015)

    Article  CAS  Google Scholar 

  3. M. Li et al., Composition design and medical application of liposomes. Eur. J. Med. Chem. 164, 640–653 (2019)

    Article  CAS  PubMed  Google Scholar 

  4. J. Qian, Y. Guo, Y. Xu, X. Wang, J. Chen, X. Wu, Combination of micelles and liposomes as a promising drug delivery system: a review. Drug Deliv. Transl. Res. 13, 2767–2789 (2023)

    Article  PubMed  Google Scholar 

  5. S. Pande, Liposomes for drug delivery: review of vesicular composition, factors affecting drug release and drug loading in liposomes. Artif. Cells Nanomed. Biotechnol. 51, 428–440 (2023)

    Article  CAS  PubMed  Google Scholar 

  6. T.M. Allen, P.R. Cullis, Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev. 65, 36–48 (2013)

    Article  CAS  PubMed  Google Scholar 

  7. V. Makwana, J. Karanjia, T. Haselhorst, S. Anoopkumar-Dukie, S. Rudrawar, Liposomal doxorubicin as targeted delivery platform: current trends in surface functionalization. Int. J. Pharm. 593, 120117 (2021)

    Article  CAS  PubMed  Google Scholar 

  8. M. Kapoor, D.J. Burgess, Efficient and safe delivery of siRNA using anionic lipids: formulation optimization studies. Int. J. Pharm. 432, 80–90 (2012)

    Article  CAS  PubMed  Google Scholar 

  9. S. Giordani, V. Marassi, A. Zattoni, B. Roda, P. Reschiglian, Liposomes characterization for market approval as pharmaceutical products: analytical methods, guidelines and standardized protocols. J. Pharm. Biomed. Anal. 236, 115751 (2023)

    Article  CAS  PubMed  Google Scholar 

  10. Q. Zhong et al., Structural and componential design: new strategies regulating the behavior of lipid-based nanoparticles. Biomater. Sci. 11, 4774–4788 (2023)

    Article  CAS  PubMed  Google Scholar 

  11. T. Sugiki, K. Furuita, T. Fujiwara, C. Kojima, Current NMR techniques for structure-based drug discovery. Molecules 23, 148 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  12. T. Sugiki et al., Real-time monitoring of enzyme-catalyzed phosphoribosylation of anti-influenza prodrug favipiravir by time-lapse nuclear magnetic resonance spectroscopy. NMR Biomed. 36, e4888 (2023)

    Article  CAS  PubMed  Google Scholar 

  13. N.W. Lutz, P.J. Cozzone, Principles of multiparametric optimization for phospholipidomics by 31P NMR spectroscopy. Biophys. Rev. 5, 295–304 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. M. Jakubec, J. Maple-Grødem, S. Akbari, S. Nesse, Ø. Halskau, A.E. Mork-Jansson, Plasma-derived exosome-like vesicles are enriched in lyso-phospholipids and pass the blood-brain barrier. PLoS ONE 15, e0232442 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. A. Jash, A. Ubeyitogullari, S.S.H. Rizvi, Synthesis of multivitamin-loaded heat stable liposomes from milk fat globule membrane phospholipids by using a supercritical-CO2 based system. Green Chem. 22, 5345–5356 (2020)

    Article  CAS  Google Scholar 

  16. A. Takeda, A. Tachibana, H. Nagumo, K. Sakai-Kato, An in vitro lipid-mixing assay to investigate the fusion between small extracellular vesicles and endosome. Anal. Biochem. 669, 115130 (2023)

    Article  CAS  PubMed  Google Scholar 

  17. B.S. Pattni, V.V. Chupin, V.P. Torchilin, New Developments in Liposomal Drug Delivery. Chem. Rev. 115, 10938–10966 (2015)

    Article  CAS  PubMed  Google Scholar 

  18. Z. Liu et al., Micelle-contained and PEGylated hybrid liposomes of combined gemcitabine and cisplatin delivery for enhancing antitumor activity. Int. J. Pharm. 602, 120619 (2021)

    Article  CAS  PubMed  Google Scholar 

  19. S. Dadpour et al., The role of size in PEGylated liposomal doxorubicin biodistribution and anti-tumour activity. IET Nanobiotechnol. 16, 259–272 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  20. A.K. Kenworthy, K. Hristova, D. Needham, T.J. McIntosh, Range and magnitude of the steric pressure between bilayers containing phospholipids with covalently attached poly(ethylene glycol). Biophys. J. 68, 1921–1936 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. O. Garbuzenko, Y. Barenholz, A. Priev, Effect of grafted PEG on liposome size and on compressibility and packing of lipid bilayer. Chem. Phys. Lipids 135, 117–129 (2005)

    Article  CAS  PubMed  Google Scholar 

  22. J. Tang, R. Kuai, W. Yuan, L. Drake, J.J. Moon, A. Schwendeman, Effect of size and pegylation of liposomes and peptide-based synthetic lipoproteins on tumor targeting. Nanomedicine 13, 1869–1878 (2017)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Profs. Reiko Seki, Michiko Sato, and Ken-ichiro Nagai (Kitasato University) for technical support in NMR experiments. This work was financially supported in part by JSPS KAKENHI (Grant No. 22H02754) of K.S-K.

Author information

Authors and Affiliations

  1. School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Nanako Endo, Chisa Aoki, Toshihiko Sugiki & Kumiko Sakai-Kato

Authors
  1. Nanako Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chisa Aoki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshihiko Sugiki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kumiko Sakai-Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kumiko Sakai-Kato.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 382 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

Endo, N., Aoki, C., Sugiki, T. et al. Quantitative lipid composition characterization of intact liposomes via 31P nuclear magnetic resonance spectroscopy. ANAL. SCI. 40, 871–879 (2024). https://doi.org/10.1007/s44211-024-00519-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s44211-024-00519-5

Keywords

Search

Navigation