Skip to main content

Regulation of Properties of Lipid Membranes by Interaction with 2-Hydroxypropyl β-Cyclodextrin: Molecular Details

Abstract

The interaction between 2-hydroxypropyl β-cyclodextrin (HPCD) and a liposomal bilayer has been studied. The main binding sites of HPCD on the surface of neutral liposomes based on dipalmitoylphosphatidylcholine (DPPC) are the phosphate groups of lipids. The complex formation with HPСD leads to the stabilization of the gel state of monocomponent liposomes. The inclusion of the anionic component, cardiolipin (CL, 20%), in the bilayer changes the nature of the liposome-HPCD interaction. The observed lipid disorder disturbs membrane integrity, which is revealed in the release of the included dye (phenolphthalein). The effect of HPCD on the process and parameters of the phase transition of anionic liposomes has been studied using thermograms, which show the change in the position of the absorption bands of lipid acyl chains in the FTIR spectrum of liposomes. A stratification of DPPC/CL (80/20%) bilayer into two microphases with different cardiolipin content has been detected. HPCD causes the more pronounced stratification in the bilayer, i.e., membrane destabilization near the melting point of CL-rich microphase and, vice versa, a decrease in the lipid mobility in regions with a low CL content. We have studied the effect of HPCD on the interaction of an antibacterial drug, levofloxacin (LV), with the lipid bilayer. It has been found that the complexation of the drug molecules with HPCD leads to an increase in the efficiency of drug adsorption on the surface of the bilayer. This may facilitate the transport of the drug through the bilayer due to the formation of defects in the membrane. LV in the complex with HPCD shows a high antibacterial efficiency in vitro against E. coli, which is not lower as compared with free LV.

This is a preview of subscription content, access via your institution.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.

REFERENCES

  1. Loftsson, T., Jarho, P., Masson, M., and Jarvinen, T., Adv. Drug Deliv. Rev., 2005, vol. 36, pp. 335–346. https://doi.org/10.1016/S0169-409X(98)00051-9

    Article  Google Scholar 

  2. Stella, V.J. and He, Q., Toxicol. Pathol., 2008, vol. 36, pp. 30–42. https://doi.org/10.1177/0192623307310945

    CAS  Article  PubMed  Google Scholar 

  3. Crini, G., Fourmentin, S., Fenyvesi, E., Torri, G., Fourmentin, M., and Morin-Crini, N., Environ. Chem. Lett. Springer Int. Publ., 2018, vol. 16, no. 4, pp. 1361–1375. https://doi.org/10.1007/s10311-018-0763-2

    CAS  Article  Google Scholar 

  4. Del Valle, E.M.M., Process Biochem., 2004, vol. 39, pp. 1033–1046. https://doi.org/10.1016/S0032-9592(03)00258-9

    CAS  Article  Google Scholar 

  5. Davis, M.E. and Brewster, M., Nat. Rev. Drug Discov., 2004, vol. 3, pp. 1023–1035. https://doi.org/10.1038/nrd1576

    CAS  Article  PubMed  Google Scholar 

  6. Le-Deygen, I.M., Skuredina, A.A., Uporov, I.V., and Kudryashova, E.V., Anal. Bioanal. Chem., 2017, vol. 409, pp. 6451–6462. https://doi.org/10.1007/s00216-017-0590-5

    CAS  Article  PubMed  Google Scholar 

  7. Skuredina, A.A., Le-Deygen, I.M., Uporov, I.V., and Kudryashova, E.V., Colloid J., 2017, vol. 79, pp. 668–676.

    CAS  Article  Google Scholar 

  8. Skuredina, A.A., Le-Deygen, I.M., and Kudryashova, E.V., Colloid J., 2018, vol. 80, pp. 312–319. https://doi.org/10.1134/S1061933X17050143

    CAS  Article  Google Scholar 

  9. Saltzman, W.M. and Kyriakides, T.R., in Principles of Tissue Engineering, 4th ed., Elsevier, 2013, pp. 385–406. https://doi.org/10.1016/B978-0-12-398358-9.00020-3

    Book  Google Scholar 

  10. Schulz, M., Olubummo, A., and Binder, W.H., Soft Matter., 2012, vol. 8, no. 18, pp. 4849–4864. https://doi.org/10.1039/c2sm06999g

    CAS  Article  Google Scholar 

  11. Hammoud, Z., Khreich, N., Auezova, L., Fourmentin, S., Elaissari, A., and Greige-Gerges, H., Int. J. Pharm. Elsevier, 2019, vol. 564, pp. 59–76. https://doi.org/10.1016/j.ijpharm.2019.03.063

    CAS  Article  Google Scholar 

  12. Challa, R., Ahuja, A., Ali, J., and Khar, R.K., AAPS Pharm. Sci. Tech., 2005, vol. 2, pp. 329–357. https://doi.org/10.1517/17425247.2.1.335

  13. Le-Deygen, I.M., Skuredina, A.A., Safronova, A.S., Yakimov, I.D., Kolmogorov, I.M., Deygen, D.M., Burova, T.V., Grinberg, N.V., Grinberg, V.Y., and Kudryashova, E.V., Chem. Phys. Lipids. Elsevier Ireland Ltd, 2020, vol. 228, p. 104 891. https://doi.org/10.1016/j.chemphyslip.2020.104891

    CAS  Article  Google Scholar 

  14. Le-Deigen, I.M., Skuredina, A.A., and Kudryashova, E.V., Russ. J. Bioorg. Chem., 2020 (in press).

  15. Deygen, I.M., Seidl, C., Kolmel, D.K., Bednarek, C., Heissler, S., Kudryashova, E.V., Brase, S., and Schepers, U., Langmuir, 2016, vol. 32, pp. 10 861–10 869. https://doi.org/10.1021/acs.langmuir.6b01023

    CAS  Article  Google Scholar 

  16. Piel, G., Piette, M., Barillaro, V., Castagne, D., Evrard, B., and Delattre, L., Int. J. Pharm., 2007, vol. 338, pp. 35–42. https://doi.org/10.1016/j.ijpharm.2007.01.015

    CAS  Article  PubMed  Google Scholar 

  17. Yaroslavov, A.A., Efimova, A.A., Lobyshe, V.I., and Kabanov, V.A., Biochim. Biophys. Acta, 2002, vol. 1560, pp. 14–24. https://doi.org/10.1016/S0005-2736(01)00453-9

    CAS  Article  PubMed  Google Scholar 

  18. Bilge, D., Sahin, I., Kazanci, N., and Severcan, F., Spectrochim. Acta, A: Mol. Biomol. Spectrosc., Elsevier, 2014, vol. 130, pp. 250–256. https://doi.org/10.1016/j.saa.2014.04.027

    Book  Google Scholar 

  19. Donova, M.V., Nikolayeva, V.M., Dovbnya, D.V., Gulevskaya, S.A., and Suzina, N.E., Microbiology, 2007, vol. 153, pp. 1981–1992. https://doi.org/10.1099/mic.0.2006/001636-0

    CAS  Article  PubMed  Google Scholar 

  20. Le-Deygen, I.M., Vlasova, K.Y., Kutsenok, E.O., Usvaliev, A.D., Efremova, M.V., Zhigachev, A.O., Rudakovskaya, P.G., Golovin, D.Y., Gribanovsky, S.L., Kudryashova, E.V., Majouga, A.G., Golovin, Y.I., Kabanov, A.V., and Klyachko, N.L., Nanomed., Nanotechnol., Biol. Med., Elsevier Inc, 2019, vol. 21, p. 102 065. https://doi.org/10.1016/j.nano.2019.102065

    Book  Google Scholar 

  21. Hatzi, P., Mourtas, S.G., Klepetsanis, P., Antimisiaris, S.G., Int. J. Pharm., 2007, vol. 333, pp. 167–176. https://doi.org/10.1016/j.ijpharm.2006.09.059

    CAS  Article  PubMed  Google Scholar 

  22. Angelini, G., Campestre, C., Boncompagni, S., and Gasbarri, C., Chem. Phys. Lipids, Elsevier Ireland Ltd., 2017, vol. 209, pp. 61–65. https://doi.org/10.1016/j.chemphyslip.2017.09.004

    CAS  Article  Google Scholar 

  23. Bertucci, C., Pistolozzi, M., and De Simone, A., Anal. Bioanal. Chem., 2010, vol. 398, pp. 155–166. https://doi.org/10.1007/s00216-010-3959-2

    CAS  Article  PubMed  Google Scholar 

  24. Chamseddin, C. and Jira, T., Curr. Pharm. Anal., 2013, vol. 9, pp. 121–129.

    CAS  Google Scholar 

  25. Goddard, J.M., Caput, D., Williams, S.R., and Martin, D.M., Proc. Natl. Acad. Sci. U. S. A., vol. 80, pp. 4281–4285. https://doi.org/10.1073/pnas.80.14.4281

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. A. Skuredina.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies with the use of humans as objects of research.

Conflict of Interest

The authors state that there is no conflict of interest.

Additional information

Translated by A. Levina

Abbreviations: HPCD, 2-hydroxypropyl β-cyclodextrin; DPPC, dipamitoylphosphatidylcholine; CL, cardiolipin; LV, levofloxacin; MIC, minimal inhibitory concentration; PP, phenolphthalein; CD, cyclodextrin.

Corresponding author: phone: +7 (495) 939-34-34; e-mail: skuredinanna@gmail.com.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Skuredina, A.A., Tychinina, A.S., Le-Deygen, I.M. et al. Regulation of Properties of Lipid Membranes by Interaction with 2-Hydroxypropyl β-Cyclodextrin: Molecular Details. Russ J Bioorg Chem 46, 692–701 (2020). https://doi.org/10.1134/S1068162020050246

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162020050246

Keywords:

  • cyclodextrins
  • liposomes
  • FTIR spectroscopy
  • CD spectroscopy
  • phase transition
  • antibacterial activity