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The Application of Coarse-Grained Molecular Dynamics to the Evaluation of Liposome Physical Stability

  • Research Article
  • Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
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Abstract

Physical stability is one of critical characteristics of liposome, especially to its clinical application. Vesicle fusion was one of the common physical stability phenomena that occurred during the long storage period. Because vesicle fusion could be easily checked by the change of vesicle size, it was widely applied in the evaluation of liposome physical stability. However, since the method requires the liposome to be placed under certain conditions for long-term observation, a liposome physical stability test usually takes several weeks, which greatly hinders the research efficiency. In this study, to speed up the research efficiency, coarse-grained molecular dynamics was first applied in the study of liposome physical stability. By analyzing the microprocess of vesicle fusion, two parameters including diffusion constant and the total time of the vesicle morphology transition process were employed to study the liposome physical stability. Then, in order to verify the applicability of two parameters, the physical stability of elastic liposomes and conventional liposomes was compared at 3 different temperatures. It was found that the fusion probability and speed of elastic liposomes were higher than those of conventional liposomes. Thus, elastic liposomes showed a worse physical stability compared with that of conventional liposomes, which was consistent with former research. Through this research, a new efficient method based on coarse-grained molecular dynamics was proposed for the study of liposome physical stability.

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References

  1. Felice B, Prabhakaran MP, Rodríguez AP, Ramakrishna S. Drug delivery vehicles on a nano-engineering perspective. Mater Sci Eng C Mater Biol Appl. 2014;41:178–95.

    Article  CAS  PubMed  Google Scholar 

  2. Pastore MN, Kalia YN, Horstmann M, Roberts MS. Transdermal patches: history, development and pharmacology. Br J Pharmacol. 2015;172(9):2179–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Abu Lila AS, Ishida T. Liposomal delivery systems: design optimization and current applications. Biol Pharm Bull. 2017;40(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  4. Crommelin DJA. Influence of lipid composition and ionic strength on the physical stability of liposomes. J Pharm Sci. 1984;73(11):1559–63.

    Article  CAS  PubMed  Google Scholar 

  5. Yotsuyanagi T, et al. Effect of cholesterol on liposome stability to ultrasonic disintegration and sodium cholate solubilization. Chem Pharm Bull (Tokyo). 1987;35(3):1228–33.

    Article  CAS  Google Scholar 

  6. Brown PM, Silvius JR. Stability and fusion of lipid vesicles containing headgroup-modified analogues of phosphatidylethanolamine. Biochim Biophys Acta. 1989;980(2):181–90.

    Article  CAS  PubMed  Google Scholar 

  7. Armengol X, Estelrich J. Physical stability of different liposome compositions obtained by extrusion method. J Microencapsul. 1995;12(5):525–35.

    Article  CAS  PubMed  Google Scholar 

  8. Casals E, Galán AḾ, Escolar G, Gallardo M, Estelrich J. Physical stability of liposomes bearing hemostatic activity. Chem Phys Lipids. 2003;125(2):139–46.

    Article  CAS  PubMed  Google Scholar 

  9. Muller M, Katsov K, Schick M. Biological and synthetic membranes: what can be learned from a coarse-grained description? Phys Rep. 2006;434(5–6):113–76.

    Article  Google Scholar 

  10. Shillcock JC, Lipowsky R. The computational route from bilayer membranes to vesicle fusion. J Phys Condens Matter. 2006;18(28):S1191–219.

    Article  CAS  PubMed  Google Scholar 

  11. Marrink SJ, de Vries AH, Tieleman DP. Lipids on the move: simulations of membrane pores, domains, stalks and curves. Biochim Biophys Acta. 2009;1788(1):149–68.

    Article  CAS  PubMed  Google Scholar 

  12. Fuhrmans M, Marelli G, Smirnova YG, Müller M. Mechanics of membrane fusion/pore formation. Chem Phys Lipids. 2015;185:109–28.

    Article  CAS  PubMed  Google Scholar 

  13. Promsri S, Ullmann GM, Hannongbua S. Molecular dynamics simulation of HIV-1 fusion domain-membrane complexes: insight into the N-terminal gp41 fusion mechanism. Biophys Chem. 2012;170:9–16.

    Article  CAS  PubMed  Google Scholar 

  14. Li R, Song D, Zhu Z, Xu H, Liu S. An induced pocket for the binding of potent fusion inhibitor CL-385319 with H5N1 influenza virus hemagglutinin. PLoS One. 2012;7(8):e41956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Iliopoulou M, Nolan R, Alvarez L, Watanabe Y, Coomer CA, Jakobsdottir GM, et al. A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction. Nat Struct Mol Biol. 2018;25(9):814–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Larsson P, Kasson PM. Lipid tail protrusion in simulations predicts fusogenic activity of influenza fusion peptide mutants and conformational models. PLoS Comput Biol. 2013;9(3):e1002950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chien L, Chen WK, Liu ST, Chang CR, Kao MC, Chen KW, et al. Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons. Oncotarget. 2015;6(31):30628–39.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Falkenstein K, De Lozanne A. Dictyostelium LvsB has a regulatory role in endosomal vesicle fusion. J Cell Sci. 2014;127(Pt 20):4356–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sharma S, Lindau M. Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex. Proc Natl Acad Sci U S A. 2018;115(50):12751–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. McDargh ZA, Polley A, O’Shaughnessy B. SNARE-mediated membrane fusion is a two-stage process driven by entropic forces. FEBS Lett. 2018;592(21):3504–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Risselada HJ, Kutzner C, Grubmuller H. Caught in the act: visualization of SNARE-mediated fusion events in molecular detail. Chembiochem. 2011;12(7):1049–55.

    Article  CAS  PubMed  Google Scholar 

  22. Tsai HH, Chang CM, Lee JB. Multi-step formation of a hemifusion diaphragm for vesicle fusion revealed by all-atom molecular dynamics simulations. Biochim Biophys Acta. 2014;1838(6):1529–35.

    Article  CAS  PubMed  Google Scholar 

  23. Marrink SJ, Mark AE. The mechanism of vesicle fusion as revealed by molecular dynamics simulations. J Am Chem Soc. 2003;125(37):11144–5.

    Article  CAS  PubMed  Google Scholar 

  24. Shillcock JC. Vesicles and vesicle fusion: coarse-grained simulations. Methods Mol Biol. 2013;924:659–97.

    Article  CAS  PubMed  Google Scholar 

  25. Arnarez C, Uusitalo JJ, Masman MF, Ingólfsson HI, de Jong DH, Melo MN, et al. Dry Martini, a coarse-grained force field for lipid membrane simulations with implicit solvent. J Chem Theory Comput. 2015;11(1):260–75.

    Article  CAS  PubMed  Google Scholar 

  26. Liu YT, Li YR, Wang X. Dynamic evolution of a vesicle formed by comb-like block copolymer-tethered nanoparticles: a dissipative particle dynamics simulation study. Phys Chem Chem Phys. 2017;19(40):27313–9.

    Article  CAS  PubMed  Google Scholar 

  27. Kasson PM, Pande VS. Control of membrane fusion mechanism by lipid composition: predictions from ensemble molecular dynamics. PLoS Comput Biol. 2007;3(11):e220.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kawamoto S, Klein ML, Shinoda W. Coarse-grained molecular dynamics study of membrane fusion: curvature effects on free energy barriers along the stalk mechanism. J Chem Phys. 2015;143(24):243112.

    Article  PubMed  Google Scholar 

  29. Elhissi AMA, Giebultowicz J, Stec AA, Wroczynski P, Ahmed W, Alhnan MA, et al. Nebulization of ultradeformable liposomes: the influence of aerosolization mechanism and formulation excipients. Int J Pharm. 2012;436(1–2):519–26.

    Article  CAS  PubMed  Google Scholar 

  30. Benson HA. Elastic liposomes for topical and transdermal drug delivery. Curr Drug Deliv. 2009;6(3):217–26.

    Article  CAS  PubMed  Google Scholar 

  31. Hussain A, Singh S, Sharma D, Webster T, Shafaat K, Faruk A. Elastic liposomes as novel carriers: recent advances in drug delivery. Int J Nanomedicine. 2017;12:5087–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kawamoto S, Shinoda W. Free energy analysis along the stalk mechanism of membrane fusion. Soft Matter. 2014;10(17):3048–54.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. School of Chinese Materia Medica, Bei**g University of Chinese Medicine, Bei**g, 102488, China

    Li** Chen, Zhimin Wu, **-Chen-Aff1">Li** Chen

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  2. Zhimin Wu
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  3. **aowen Wu
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  4. Yuyao Liao
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  5. **ngxing Dai
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  6. **nyuan Shi
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Correspondence to **%20Chen%20et%20al&contentID=10.1208%2Fs12249-020-01680-6&copyright=American%20Association%20of%20Pharmaceutical%20Scientists&publication=1530-9932&publicationDate=2020-05-17&publisherName=SpringerNature&orderBeanReset=true">Reprints and permissions

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Chen, L., Wu, Z., Wu, X. et al. The Application of Coarse-Grained Molecular Dynamics to the Evaluation of Liposome Physical Stability. AAPS PharmSciTech 21, 138 (2020). https://doi.org/10.1208/s12249-020-01680-6

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  • DOI: https://doi.org/10.1208/s12249-020-01680-6

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