Skip to main content
SpringerLink
Log in

Spherical and tubular dimyristoylphosphatidylcholine liposomes

Phase transition induced by pinocembrin

  • Published:
Journal of Thermal Analysis and Calorimetry Aims and scope Submit manuscript

Abstract

A physicochemical study of the interaction of pinocembrin with dimyristoylphosphatidylcholine (DMPC) liposomes was carried out. Unilamellar vesicles of about 100 nm were prepared. Pinocembrin was incorporated into the lipid membrane by interacting strongly with the acyl groups of the phospholipid chains, favoring the fluid phase. The incorporation efficiency was 89%. At concentrations higher than 0.436 mg mL−1 of pinocembrin, a change of structure from spherical to tubular liposomes was observed, and the enthalpy of this transition was determined by differential scanning calorimetry. After 0.744 mg mL−1, there was no change in the transition enthalpy from gel phase to liquid crystalline, so it is possible to assume that the lipid membrane reached saturation. With the findings presented in this research, it is possible to increase the solubility and bioavailability of the pinocembrin by using DMPC as a molecular carrier, enhancing its use as drug in the pharmaceutical industry to treat cancer, ischemic stroke, intracerebral hemorrhage, Alzheimer’s disease, cardiovascular diseases and atherosclerosis as well as other diseases.

Graphic 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
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Fidler MM, Bray F, Soerjomataram I. The global cancer burden and human development: a review. Scand J Public Health. 2018;46:27–36.

    Article  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    Article  CAS  Google Scholar 

  3. Rasul A, Millimouno FM, Ali Eltayb W, Ali M, Li J, Li X. Pinocembrin: a novel natural compound with versatile pharmacological and biological activities. BioMed Res Int. 2013. https://doi.org/10.1155/2013/379850.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Aygun A, Torrey K, Kumar A, Stephenson LD. Investigation of factors affecting controlled release from photosensitive DMPC and DSPC liposomes. Appl Biochem Biotechnol. 2012;167:743–57.

    Article  CAS  Google Scholar 

  5. Ruddock PS, Charland M, Ramirez S, López A, Towers GHN, Arnason JT, et al. Antimicrobial activity of flavonoids from Piper lanceaefolium and other Colombian medicinal plants against antibiotic susceptible and resistant strains of Neisseria gonorrhoeae. Sex Transm Dis. 2011;38:82–8.

    Article  CAS  Google Scholar 

  6. Chen Z, Rasul A, Zhao C, Millimouno FM, Tsuji I, Yamamura T, et al. Antiproliferative and apoptotic effects of pinocembrin in human prostate cancer cells. Bangladesh J Pharmacol. 2013;8:255–62.

    Article  Google Scholar 

  7. Charoensin S, Punvittayagul C, Pompimon W, Mevatee U, Wongpoomchai R. Toxicological and clastogenic evaluation of pinocembrin and pinostrobin isolated from Boesenbergia pandurata in Wistar rats. Thai J Toxicol. 2010;25:29–40.

    Google Scholar 

  8. Liu R, Gao M, Yang ZH, Du GH. Pinocembrin protects rat brain against oxidation and apoptosis induced by ischemia-reperfusion both in vivo and in vitro. Brain Res. 2008;1216:104–15.

    Article  CAS  Google Scholar 

  9. Zheng Y, Wang K, Wu Y, Chen Y, Chen X, Hu CW, et al. Pinocembrin induces ER stress mediated apoptosis and suppresses autophagy in melanoma cells. Cancer Lett. 2018;431:31–42. https://doi.org/10.1016/j.canlet.2018.05.026.

    Article  CAS  PubMed  Google Scholar 

  10. Lan X, Wang W, Li Q, Wang J. The natural flavonoid pinocembrin: molecular targets and potential therapeutic applications. Mol Neurobiol. 2016;53:1794–801. https://doi.org/10.1007/s12035-015-9125-2.

    Article  CAS  PubMed  Google Scholar 

  11. Liu R, Li JZ, Song JK, Zhou D, Huang C, Bai XY, et al. Pinocembrin improves cognition and protects the neurovascular unit in Alzheimer related deficits. Neurobiol Aging. 2014;35:1275–85. https://doi.org/10.1016/j.neurobiolaging.2013.12.031.

    Article  CAS  PubMed  Google Scholar 

  12. Lan X, Han X, Li Q, Li Q, Gao Y, Cheng T, et al. Pinocembrin protects hemorrhagic brain primarily by inhibiting toll-like receptor 4 and reducing M1 phenotype microglia. Brain Behav Immun. 2017;61:326–39. https://doi.org/10.1016/j.bbi.2016.12.012.

    Article  CAS  PubMed  Google Scholar 

  13. Stefanutti E, Papacci F, Sennato S, Bombelli C, Viola I, Bonincontro A, et al. Cationic liposomes formulated with DMPC and a gemini surfactant traverse the cell membrane without causing a significant bio-damage. Biochim Biophys Acta - Biomembr. 2014;1838:2646–55. https://doi.org/10.1016/j.bbamem.2014.05.026.

    Article  CAS  Google Scholar 

  14. Moreno MM, Garidel P, Suwalsky M, Howe J, Brandenburg K. The membrane-activity of Ibuprofen, Diclofenac, and Naproxen: a physico-chemical study with lecithin phospholipids. Biochim Biophys Acta - Biomembr. 2009;1788:1296–303. https://doi.org/10.1016/j.bbamem.2009.01.016.

    Article  CAS  Google Scholar 

  15. Basso LGM, Rodrigues RZ, Naal RMZG, Costa-Filho AJ. Effects of the antimalarial drug primaquine on the dynamic structure of lipid model membranes. Biochim Biophys Acta - Biomembr. 2011;1808:55–64. https://doi.org/10.1016/j.bbamem.2010.08.009.

    Article  CAS  Google Scholar 

  16. Wu FG, Wu RG, Sun HY, Zheng YZ, Yu ZW. Demixing and crystallization of DODAB in DPPC-DODAB binary mixtures. Phys Chem Chem Phys. 2014;16:15307–18.

    Article  CAS  Google Scholar 

  17. Wu FG, Wang NN, Yu JS, Luo JJ, Yu ZW. Nonsynchronicity phenomenon observed during the Lamellar–Micellar phase transitions of 1-stearoyllysophosphatidylcholine dispersed in water. J Phys Chem B. 2010;114:2158–64.

    Article  CAS  Google Scholar 

  18. Wu FG, Jia Q, Wu RG, Yu ZW. Regional cooperativity in the phase transitions of dipalmitoylphosphatidylcholine bilayers: the lipid tail triggers the isothermal crystallization process. J Phys Chem B. 2011;115:8559–68.

    Article  CAS  Google Scholar 

  19. Mady MM, Shafaa MW, Abbase ER, Fahium AH. Interaction of doxorubicin and dipalmitoylphosphatidylcholine liposomes. Cell Biochem Biophys. 2012;62:481–6.

    Article  CAS  Google Scholar 

  20. Di Foggia M, Bonora S, Tinti A, Tugnoli V. DSC and Raman study of DMPC liposomes in presence of ibuprofen at different pH. J Therm Anal Calorim. 2017;127:1407–17.

    Article  Google Scholar 

  21. Taylor KMG, Morris RM. Thermal analysis of phase transition in liposomes behaviour. Thermochim Acta. 1995;248:289–301.

    Article  CAS  Google Scholar 

  22. Ohline SM, Campbell ML, Turnbull MT, Kohler SJ. Differential scanning calorimetric study of bilayer membrane phase transitions. A biophysical chemistry experiment. J Chem Educ. 2001;78:1251. https://doi.org/10.1021/ed078p1251.

    Article  CAS  Google Scholar 

  23. Lentz BR, Barenholz Y, Thompson E. Fluorescence depolarization studies of phase transitions and fluidity in phospholipid bilayers. I. Single component phosphatidylcholine liposomes. Biochemistry. 1976;15:4521–8.

    Article  CAS  Google Scholar 

  24. Jain MK, Wu NM. Effect of small molecules on the dipalmitoyl lecithin liposomal bilayer: III. Phase transition in lipid bilayer. J Membr Biol. 1977;34:157–201.

    Article  CAS  Google Scholar 

  25. Harris JS, Epps DE, Davio SR, Kézdy FJ. Evidence for transbilayer, tail-to-tail cholesterol dimers in dipalmitoylglycerophosphocholine liposomes. Biochemistry. 1995;34:3851–7.

    Article  CAS  Google Scholar 

  26. El Maghraby GMM, Williams AC, Barry BW. Drug interaction and location in liposomes: correlation with polar surface areas. Int J Pharm. 2005;292:179–85.

    Article  Google Scholar 

  27. Pruchnik H. Influence of cytotoxic butyltin complexes with 2-sulfobenzoic acid on the thermotropic phase behavior of lipid model membranes. J Therm Anal Calorim. 2017;127:507–14.

    Article  CAS  Google Scholar 

  28. Wei X, Patil Y, Ohana P, Amitay Y, Shmeeda H, Gabizon A, et al. Characterization of pegylated liposomal mitomycin c lipid-based prodrug (promitil) by high sensitivity differential scanning calorimetry and cryogenic transmission electron microscopy. Mol Pharm. 2017;14:4339–45.

    Article  CAS  Google Scholar 

  29. Momo F, Fabris S, Stevanato R. Interaction of fluoxetine with phosphatidylcholine liposomes. Biophys Chem. 2005;118:15–21.

    Article  CAS  Google Scholar 

  30. Garidel P, Johann C, Blume A. Thermodynamics of lipid organization and domain formation in phospholipid bilayers. J Liposome Res. 2000;10:131–58.

    Article  CAS  Google Scholar 

  31. Subczynski WK, Wisniewska A, Subczynski WK, Wisniewska A, Yin JJ, Hyde JS, et al. Hydrophobic barriers of lipid bilayer membranes formed by reduction of water penetration by alkyl chain unsaturation and cholesterol. Biochemistry. 1994;33:7670–81.

    Article  CAS  Google Scholar 

  32. Arrowsmith M, Hadgraft J, Kellaway IW. The interaction of cortisone esters with liposomes as studied by differential scanning calorimetry. Int J Pharm. 1983;16:305–18.

    Article  CAS  Google Scholar 

  33. Fildes FJT, Oliver JE. Interaction of cortisol-21-palmitate with liposomes examined by differential scanning calorimetry. J Pharm Pharmacol. 1978;30:337–42.

    Article  CAS  Google Scholar 

  34. Wu RG, Wang YR, Wu FG, Zhou HW, Zhang XH, Hou JL. A DSC study of paeonol-encapsulated liposomes, comparison the effect of cholesterol and stigmasterol on the thermotropic phase behavior of liposomes. J Therm Anal Calorim. 2012;109:311–6.

    Article  CAS  Google Scholar 

  35. Zhang W, Wang Z, Wu C, Jin Y, Liu X, Wu Z, et al. The effect of DSPE-PEG2000, cholesterol and drug incorporated in bilayer on the formation of discoidal micelles. Eur J Pharm Sci. 2018;125:74–85. https://doi.org/10.1016/j.ejps.2018.09.013.

    Article  CAS  PubMed  Google Scholar 

  36. Neunert G, Tomaszewska-Gras J, Siejak P, Pietralik Z, Kozak M, Polewski K. Disruptive effect of tocopherol oxalate on DPPC liposome structure: DSC, SAXS, and fluorescence anisotropy studies. Chem Phys Lipids. 2018;216:104–13.

    Article  CAS  Google Scholar 

  37. Edwards K, Johnsson M, Karlsson G, Silvander M. Effect of polyethyleneglycol-phospholipids on aggregate structure in preparations of small unilamellar liposomes. Biophys J. 1997;73:258–66. https://doi.org/10.1016/S0006-3495(97)78066-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mui BL, Döbereiner HG, Madden TD, Cullis PR. Influence of transbilayer area asymmetry on the morphology of large unilamellar vesicles. Biophys J. 1995;69:930–41.

    Article  CAS  Google Scholar 

  39. Li X-C, Ferreira D, Ding Y. Determination of absolute configuration of natural products: theoretical calculation of electronic circular dichroism as a tool. Curr Org Chem. 2010;14:1678–97.

    Article  CAS  Google Scholar 

  40. Xu P, Tan G, Zhou J, He J, Lawson LB, Mcpherson GL, et al. Undulating tubular liposomes through incorporation of a synthetic skin ceramide into phospholipid bilayers. Langmuir. 2009;25:10422–5.

    Article  CAS  Google Scholar 

  41. Champion JA, Mitragotri S. Role of target geometry in phagocytosis. Proc Natl Acad Sci. 2006;103:4930–4. https://doi.org/10.1073/pnas.0600997103.

    Article  CAS  PubMed  Google Scholar 

  42. Sakuragi M, Taguchi K, Kusakabe K. Structural and biological characterization of Fe3O4-loaded spherical and tubular liposomes for use in drug delivery systems. Jpn J Appl Phys. 2017;56:055002.

    Article  Google Scholar 

  43. Svetina S, Žekš B. Shape behavior of lipid vesicles as the basis of some cellular processes. Anat Rec. 2002;268:215–25.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The present work was financially supported by Consejo Nacional de Ciencia y Tecnología de México (CONACYT, Grant 270969) and Facultad de Química (PAIP 5000-9020). We are grateful to Rafael Ibarra for his help provided in the language revision, Dra. Josefa Bernard and Dr. Ismael Bustos Jaimes for her support with Nanosizer equipment, Dr. Francisco Javier de la Mora Bravo, Q.F.B. Tereso Ballado Nava and Dr. Georges Dreyfus for allowing me to use the extruder, Dr. Rafael Ivan Puente Lee from Unidad de Servicios de Apoyo a la Investigación y a la Industria (USAI, UNAM) for his assistance in obtaining microscopies and Dr. Efren Hernández for his valuable comments.

Author information

Authors and Affiliations

  1. Laboratorio de Biofisicoquímica, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico

    Elizabeth Uria-Canseco & Silvia Perez-Casas

Authors
  1. Elizabeth Uria-Canseco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvia Perez-Casas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Silvia Perez-Casas.

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

Uria-Canseco, E., Perez-Casas, S. Spherical and tubular dimyristoylphosphatidylcholine liposomes. J Therm Anal Calorim 139, 399–409 (2020). https://doi.org/10.1007/s10973-019-08416-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10973-019-08416-0

Keywords

Search

Navigation