Funct. Mater. 2022; 29 (1): 100-106.

doi:https://doi.org/10.15407/fm29.01.100

Dimethyl sulfoxide as a functional agent for antimicrobial drug's transport facilitating: mechanistic study by mass spectrometry

V.A.Pashynska1, M.V.Kosevich1, A.Gomory2, L.Drahos2

1B.Verkin Institute for Low Temperature Physics and Engineering, National Academy of Sciences of Ukraine, 47 Nauky Ave., 61103 Kharkiv, Ukraine
2Institute of Organic Chemistry of Research Centre for Natural Sciences, Magyar tudosok korutja 2, H-1117 Budapest, Hungary

Abstract: 

Electrospray ionization mass spectrometry (ESI MS) study has been performed to examine biologically significant intermolecular interactions between the molecules of dimethyl sulfoxide (DMSO, known as a functional agent for transdermal and transmembrane drug's transfer facilitation) and some antimicrobial drugs. Formation of stable noncovalent complexes of DMSO with the molecules of antibiotics levofloxacin (LEF) and cycloserine (CYS) in the polar solvent methanol has been revealed by ESI MS probing of model binary systems of DMSO with the mentioned drugs. At the same time ESI MS investigation of the similar model systems containing DMSO and antimicrobial chemotherapeutic preparation decamethoxinum (DEC) has shown that any peaks of the noncovalent complexes between DMSO and DEC are not recorded in the mass spectra, that points to the dependence of DMSO-drug complexation peculiarities on the drug's structure. The data of ESI MS examining of DMSO+dipalmitoylphosphatidylcholine model system reveal that the DMSO molecules also do not form stable noncovalent clusters with the membrane phospholipid molecules in the polar surrounding. The obtained results as to formation of stable noncovalent complexes of DMSO with LEF and CYS in the polar solvent are proposed to be considered as one of the possible molecular mechanisms of action of DMSO as transdermal and transmembrane penetration enhancer in drug delivery. The current study confirms the ESI MS method applicability to examining the DMSO complexation with the drugs molecules and biomolecules with the purpose to predict the DMSO usage efficiency as an agent for the drug's transdermal and transmembrane transport facilitating.

Keywords: 
dimethyl sulfoxide, antibiotics, electrospray ionization mass spectrometry, noncovalent complexes, transmembrane transfer facilitation.
References: 

1. Biomaterials for Drug Delivery: Sources, Classification, Synthesis, Processing, and Applications, by S.O.Adeosun, M.O.Ilomuanya, O.P.Gbenebor, M.O.Dada and C.C.Odili, in: Advanced Functional Materials, ed. by N.Tasaltin, P.S.Nnamchi and S.Saud (2020), p.176-210. https://doi.org/10.5772/intechopen.93368

2. A.C.Williams, B.W.Barry, Adv. Drug Deliv. Rev., 56, 603 (2004). https://doi.org/10.1016/j.addr.2003.10.025

3. V.Pashynska, S.Stepanian, A.Gomory et al., J. Mol. Struct., 1146, 441 (2017). http://dx.doi.org/10.1016/j.molstruc.2017.06.007

4. V.A.Pashynska, M.V.Kosevich, Biophys. Bull., 42, 28 (2019). https://doi.org/10.26565/2075-3810-2019-42-03

5. V.A.Pashynska, N.M.Zholobak, M.V.Kosevich et al., Biophys. Bull., 39, 15 (2018). https://doi.org/10.26565/2075-3810-2018-39-02

6. V.Pashynska, S.Stepanian, A.Gomory et al., Chem. Phys., 455, 81(2015). http://dx.doi.org/10.1016/j.chemphys.2015.04.014

7. K.Capriotti, J.A.Capriotti, J. Clin. Aesthe.t Dermatol., 5, 24 (2012).

8. A.K.Sum, J.J.dePablo, Biophys. J., 85, 3636 (2003). https://doi.org/10.1016/S0006-3495(03)74781-X

9. R.Notman, M.Noro, B.O'Malley et al., J. Am. Chem. Soc., 128, 13982 (2006). https://pubs.acs.org/doi/10.1021/ja063363t

10. A.A.Gurtovenko, J.Anwar, J. Phys. Chem. B, 111, 10453 (2007). https://doi.org/10.1021/jp073113e

11. M.A.deMenorval, L.M.Mir, M.L Fernandez et al., PLOS One, 7, e41733 (2012). https://doi.org/10.1371/journal.pone.0041733

12. Z.E.Hughes, A.E.Mark, R.L.Mancera, J. Phys. Chem. B, 116, 11911 (2012). https://doi.org/10.1021/jp3035538

13. C.-Y.Cheng, J.Song, J.Pas et al., Biophys. J., 109, 330 (2015). https://doi.org/10.1016/j.bpj.2015.06.011

14. Y.Lee, P.A.Pincus, C.Hyeon, Biophys. J., 111, 2481 (2016). https://doi.org/10.1016/j.bpj.2016.10.033

15. S.A.Kirsch, R.A.Bockmann, Biochim. Biophys. Acta (BBA) - Biomembranes, 1858, 2266 (2016). https://doi.org/10.1016/j.bbamem.2015.12.031

16. Shobhna, M.Kumari, H.K.Kashyapa, J. Chem. Phys., 153, 035104 (2020). https://doi.org/10.1063/5.0014614

17. B.Gironi, Z.Kahveci, B.McGill et al., Biophys. J., 119, 274 (2020). https://doi.org/10.1016/j.bpj.2020.05.037

18. N.A.Kasian, O.V.Vashchenko, L.V.Budianska et al., Biochim. Biophys. Acta (BBA) - Biomembranes, 1861, 123 (2019). https://doi.org/10.1016/j.bbamem.2018.08.007

19. A.A.Gurtovenko, J.Anwar, J. Phys. Chem. B, 111, 13379 (2007). https://doi.org/10.1021/jp075631v

20. V.A.Pashynska., M.V.Kosevich, H.Van den Heuvel et al., Rapid Commun. Mass Spectrom., 20, 755 (2006). https://doi.org/10.1002/rcm.2371

21. V.Pashynska, M.Kosevich, S.Stepanian, L.Adamowicz, J. Mol. Struct.:THEOCHEM, 815, 55 (2007). https://doi.org/10.1016/j.theochem.2007.03.019

Current number: