Study of aqueous solutions of poloxamers by rotational viscometry and spin probe method

Authors

DOI:

https://doi.org/10.15587/2519-4852.2023.285933

Keywords:

poloxamer, solution, gel, viscosity, micelle, spin probe, EPR spectrum, spectrum parameters

Abstract

The aim. To study aqueous solutions of different poloxamers by spin probe method and rotational viscometry depending on the temperature and poloxamer content.

Materials and methods. The aqueous solutions of poloxamers 188, 237, 338 and 407 were studied. The solutions were studied by rotational viscometry at different temperatures; the flow behaviour, yield stress (t0), and dynamic or apparent viscosity (η) were determined. Five spin probes differing in molecular structure, solubility, and radical localisation were introduced into the solutions. Electron paramagnetic resonance (EPR) spectra were obtained. The EPR spectra were used to determine their type and to calculate parameters.

Results. Three factors are important for gel formation: the poloxamer type, its concentration in aqueous solution, and temperature. As the temperature of aqueous solutions of poloxamers 237, 338, and 407 increases, the rotational correlation times of fatty acid-based spin probes and the order parameters of their EPR spectra decrease. This indicates a decrease in the packing density and orderliness of the polypropylene oxide (PPO) chains in the non-polar part of the poloxamer associates, leading to an increase in the volume fraction of micelles/mesophases and promoting the formation of gels. As the temperature decreases, the opposite processes occur, leading to a gel → sol transition. At 37 °C, non-polar micelle cores could be characterised as two-dimensionally liquid and one-dimensionally solid. The rotational correlation times of the hydrophilic spin probe 4-OXO-TEMPO in 25 % aqueous solutions of poloxamers 338 and 407 are approximately constant or increasing despite an increase in the temperature. This indicates that in the polar part of the poloxamer associates, where this probe is partially localised, structural rearrangements occur with increasing temperature, which probably prevents hydrophobic hydration of the PPO chains.

Conclusions. The rheological properties of aqueous solutions of poloxamers depend on their type, concentration, and temperature. According to the parameters of the EPR spectra of fatty acid-based spin probes, it was found that with increasing temperature, the packing density and the orderliness of the PPO chains in the non-polar part of the poloxamer associates decrease, probably leading to an increase in the volume of the micelles and causing a sol → gel transition

Author Biographies

Nikolay Lyapunov, State Scientific Institution «Institute for Single Crystals» of National Academy of Sciences of Ukraine

Doctor of Pharmaceutical Sciences, Professor, Leading Researcher

Laboratory of Technology and Analysis of Medicinal Products

Elena Bezuglaya, State Scientific Institution «Institute for Single Crystals» of National Academy of Sciences of Ukraine

PhD, Senior Researcher, Head of Laboratory

Laboratory of Technology and Analysis of Medicinal Products

Oleksii Liapunov, State Scientific Institution «Institute for Single Crystals» of National Academy of Sciences of Ukraine

PhD, Researcher

Laboratory of Technology and Analysis of Medicinal Products

Oleksii Lysokobylka, State Scientific Institution «Institute for Single Crystals» of National Academy of Sciences of Ukraine

Junior Researcher

Laboratory of Technology and Analysis of Medicinal Products

References

  1. The European Pharmacopoeia (2019). European Directorate for the Quality of Medicines & HealthCare of the Council of Europe, Strasbourg, 5224.
  2. Sheskey, P. J., Hancock, B. C., Moss, G. P., Goldfarb, D. J. (Eds.) (2020). Handbook of Pharmaceutical Excipients. London: Pharm. Press, 1296.
  3. Bodratti, A., Alexandridis, P. (2018). Formulation of Poloxamers for Drug Delivery. Journal of Functional Biomaterials, 9 (1), 11. doi: https://doi.org/10.3390/jfb9010011
  4. Bodratti, A. M., Sarkar, B., Alexandridis, P. (2017). Adsorption of poly(ethylene oxide)-containing amphiphilic polymers on solid-liquid interfaces: Fundamentals and applications. Advances in Colloid and Interface Science, 244, 132–163. doi: https://doi.org/10.1016/j.cis.2016.09.003
  5. Mortensen, K., Talmon, Y. (1995). Cryo-TEM and SANS Microstructural Study of Pluronic Polymer Solutions. Macromolecules, 28 (26), 8829–8834. doi: https://doi.org/10.1021/ma00130a016
  6. Alexandridis, P., lan Hatton, T. (1995). Poly(ethylene oxide) poly(propylene oxide) poly(ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 96 (1-2), 1–46. doi: https://doi.org/10.1016/0927-7757(94)03028-x
  7. Alexandridis, P., Athanassiou, V., Fukuda, S., Hatton, T. A. (1994). Surface Activity of Poly(ethylene oxide)-block-Poly(propylene oxide)-block-Poly(ethylene oxide) Copolymers. Langmuir, 10 (8), 2604–2612. doi: https://doi.org/10.1021/la00020a019
  8. Alexandridis, P., Holzwarth, J. F., Hatton, T. A. (1994). Micellization of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Copolymers in Aqueous Solutions: Thermodynamics of Copolymer Association. Macromolecules, 27 (9), 2414–2425. doi: https://doi.org/10.1021/ma00087a009
  9. Raval, A., Pillai, S. A., Bahadur, A., Bahadur, P. (2017). Systematic characterization of Pluronic® micelles and their application for solubilization and in vitro release of some hydrophobic anticancer drugs. Journal of Molecular Liquids, 230, 473–481. doi: https://doi.org/10.1016/j.molliq.2017.01.065
  10. Cabana, A., Aı̈t-Kadi, A., Juhász, J. (1997). Study of the Gelation Process of Polyethylene Oxidea–Polypropylene Oxideb–Polyethylene OxideaCopolymer (Poloxamer 407) Aqueous Solutions. Journal of Colloid and Interface Science, 190 (2), 307–312. doi: https://doi.org/10.1006/jcis.1997.4880
  11. Prud’homme, R. K., Wu, G., Schneider, D. K. (1996). Structure and Rheology Studies of Poly(oxyethylene−oxypropylene−oxyethylene) Aqueous Solution. Langmuir, 12 (20), 4651–4659. doi: https://doi.org/10.1021/la951506b
  12. Soliman, K. A., Ullah, K., Shah, A., Jones, D. S., Singh, T. R. R. (2019). Poloxamer-based in situ gelling thermoresponsive systems for ocular drug delivery applications. Drug Discovery Today, 24 (8), 1575–1586. doi: https://doi.org/10.1016/j.drudis.2019.05.036
  13. Cook, M. T., Brown, M. B. (2018). Polymeric gels for intravaginal drug delivery. Journal of Controlled Release, 270, 145–157. doi: https://doi.org/10.1016/j.jconrel.2017.12.004
  14. Russo, J., Fiegel, J., Brogden, N. K. (2020). Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia. Pharmaceutics, 12 (12), 1214. doi: https://doi.org/10.3390/pharmaceutics12121214
  15. Russo, E., Villa, C. (2019). Poloxamer Hydrogels for Biomedical Applications. Pharmaceutics, 11 (12), 671. doi: https://doi.org/10.3390/pharmaceutics11120671
  16. Zhang, T., Chen, S., Dou, H., Liu, Q., Shu, G., Lin, J. et al. (2021). Novel glucosamine-loaded thermosensitive hydrogels based on poloxamers for osteoarthritis therapy by intra-articular injection. Materials Science and Engineering: C, 118, 111352. doi: https://doi.org/10.1016/j.msec.2020.111352
  17. Abdeltawab, H., Svirskis, D., Sharma, M. (2020). Formulation strategies to modulate drug release from poloxamer based in situ gelling systems. Expert Opinion on Drug Delivery, 17 (4), 495–509. doi: https://doi.org/10.1080/17425247.2020.1731469
  18. Wanka, G., Hoffmann, H., Ulbricht, W. (1990). The aggregation behavior of poly-(oxyethylene)-poly-(oxypropylene)-poly-(oxyethylene)-block-copolymers in aqueous solution. Colloid & Polymer Science, 268 (2), 101–117. doi: https://doi.org/10.1007/bf01513189
  19. Alexandridis, P., Zhou, D., Khan, A. (1996). Lyotropic Liquid Crystallinity in Amphiphilic Block Copolymers: Temperature Effects on Phase Behavior and Structure for Poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) Copolymers of Different Composition. Langmuir, 12 (11), 2690–2700. doi: https://doi.org/10.1021/la951025s
  20. Alexandridis, P., Olsson, U., Lindman, B. (1998). A Record Nine Different Phases (Four Cubic, Two Hexagonal, and One Lamellar Lyotropic Liquid Crystalline and Two Micellar Solutions) in a Ternary Isothermal System of an Amphiphilic Block Copolymer and Selective Solvents (Water and Oil). Langmuir, 14 (10), 2627–2638. doi: https://doi.org/10.1021/la971117c
  21. Sarkar, B., Venugopal, V., Bodratti, A. M., Tsianou, M., Alexandridis, P. (2013). Nanoparticle surface modification by amphiphilic polymers in aqueous media: Role of polar organic solvents. Journal of Colloid and Interface Science, 397, 1–8. doi: https://doi.org/10.1016/j.jcis.2013.01.034
  22. Valero, M., Castiglione, F., Mele, A., da Silva, M. A., Grillo, I., González-Gaitano, G., Dreiss, C. A. (2016). Competitive and Synergistic Interactions between Polymer Micelles, Drugs, and Cyclodextrins: The Importance of Drug Solubilization Locus. Langmuir, 32 (49), 13174–13186. doi: https://doi.org/10.1021/acs.langmuir.6b03367
  23. Cook, M. T., Abou-Shamat, M. A., Stair, J. L., Calvo-Castro, J. (2022). Raman spectroscopy coupled to computational approaches towards understanding self-assembly in thermoreversible poloxamer gels. Journal of Molecular Liquids, 351, 118660. doi: https://doi.org/10.1016/j.molliq.2022.118660
  24. Berliner, L. (Ed.). (1979). Metod spinovyih metok. Teoriya i primenenie. Moscow: Mir, 635.
  25. Georgieva, E. R. (2017). Nanoscale lipid membrane mimetics in spin-labeling and electron paramagnetic resonance spectroscopy studies of protein structure and function. Nanotechnology Reviews, 6 (1), 75–92. doi: https://doi.org/10.1515/ntrev-2016-0080
  26. Sahu, I. D., Lorigan, G. A. (2021). Probing Structural Dynamics of Membrane Proteins Using Electron Paramagnetic Resonance Spectroscopic Techniques. Biophysica, 1 (2), 106–125. doi: https://doi.org/10.3390/biophysica1020009
  27. Camargos, H. S., Alonso, A. (2013). Electron paramagnetic resonance (EPR) spectral components of spin-labeled lipids in saturated phospholipid bilayers: effect of cholesterol. Química Nova, 36 (6), 815–821. doi: https://doi.org/10.1590/s0100-40422013000600013
  28. Catte, A., White, G. F., Wilson, M. R., Oganesyan, V. S. (2018). Direct Prediction of EPR Spectra from Lipid Bilayers: Understanding Structure and Dynamics in Biological Membranes. ChemPhysChem, 19 (17), 2183–2193. doi: https://doi.org/10.1002/cphc.201800386
  29. Farafonov, V. S., Lebed, A. V. (2020). Nitroxyl spin probe in ionic micelles: A molecular dynamics study. Kharkiv University Bulletin. Chemical Series, 34 (57), 57–64. doi: https://doi.org/10.26565/2220-637x-2020-34-02
  30. Bezuglaya, E., Lyapunov, N., Lysokobylka, O., Liapunov, O., Klochkov, V., Grygorova, H., Liapunova, A. (2021). Interaction of surfactants with poloxamers 338 and its effect on some properties of cream base. ScienceRise: Pharmaceutical Science, 6 (34), 4–19. doi: https://doi.org/10.15587/2519-4852.2021.249312
  31. Bezuglaya, E., Lyapunov, N., Chebanov, V., Liapunov, O. (2022). Study of the formation of micelles and their structure by the spin probe method. ScienceRise: Pharmaceutical Science, 4 (38), 4–18. doi: https://doi.org/10.15587/2519-4852.2022.263054
  32. Rusanov, A. I., Shchyokin, A. K. (2016). Micelloobrazovanie v rastvorah poverhnostno-aktivnyh veshchestv. Saint-Peterburg: OOO «Izdatel'stvo «Lan'», 612.
  33. Markus, F., Dreher, F., Laschat, S., Baudis, S., Tovar, G. E. M., Southan, A. (2017). Physically and chemically gelling hydrogel formulations based on poly(ethylene glycol) diacrylate and Poloxamer 407. Polymer, 108, 21–28. doi: https://doi.org/10.1016/j.polymer.2016.11.039
  34. Lykhtenshtein, G. I. (1974). Metod spinovykh zondov v molekuliarnoi biologii, Moscow: Nauka, 256.
  35. Kuznecov, A. N. (1976). Metod spinovogo zonda (Osnovy i primenenie), Moscow: Nauka, 210.
Study of aqueous solutions of poloxamers by rotational viscometry and spin probe method

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Published

2023-08-31

How to Cite

Lyapunov, N., Bezuglaya, E., Liapunov, O., & Lysokobylka, O. (2023). Study of aqueous solutions of poloxamers by rotational viscometry and spin probe method. ScienceRise: Pharmaceutical Science, (4(44), 4–18. https://doi.org/10.15587/2519-4852.2023.285933

Issue

No. 4(44) (2023)

Section

Pharmaceutical Science

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Copyright (c) 2023 Nikolay Lyapunov, Elena Bezuglaya, Oleksii Liapunov, Oleksii Lysokobylka

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