DETERMINATION OF THE DIFFUSION COEFFICIENT FOR THE DRUG RIVANOL IN THE HUMAN BUCCAL MUCOSA IN VITRO

DOI: https://doi.org/10.29296/24999490-2019-06-07

A.A. Selifonov(1, 2), G.N. Naumova(1), V.V. Tuchin(1, 3–5) 1-Saratov State University, Astrakhanskaya str. 83, Saratov, 410012, Russian Federation; 2-Saratov State Medical University, Kazachaya str., 112 B, Saratov, 410012, Russian Federation; 3-Tomsk State University, Lenina Avenue, 36, Tomsk, 634050, Russian Federation; 4-ITMO University, Russian Federation, Kronverksky prospect, 49, Saint Petersburg, 197101, Russian Federation; 5-Institute of Precision Mechanics and Control, Rabochaya str., 24, Saratov, 410028, Russian Federation Е-mail: [email protected]

Introduction. Dyes have long been successfully used in medicine as exogenous chromophores to increase the effectiveness of the interaction of light with biological tissues, as contrast agents and photosensitizers in diagnosis and photodynamic therapy. At present, the current area of medicine is the development of methods for photodynamic therapy, both for the treatment of cancer pathologies and for antibacterial anti-inflammatory procedures, which can effectively influence resistant strains of microorganisms. The aim of the study. The work is devoted to the determination of the effective diffusion coefficient of the preparation Rivanol in the human buccal mucosa in vitro using the method of optical spectroscopy of diffuse reflection with the usage of the model of free diffusion. The active ingredient of the pharmaceutical preparation Rivanol is ethacridine lactate – acridine low toxic dye with antiseptic and photosensitizing properties, the solution of which has absorption bands in the UV/visible range of 320–450 nm, as well as fluorescence in the green. Methods. In this work, the determination of the effective diffusivity of Rivanol in biological tissue was based on measuring the kinetics of changes in the diffuse reflectance spectrum and estimating the effective optical density when fitting experimental data using the equation obtained from the second Fick law and the Beer-Lambert–Bouguer law. Results. For the first time, an effective in vitro diffusion coefficient of Rivanol in human buccal mucous was detected, which on average (n=6) accounted for (2,36±0,73)·10-7 cm2/s. Conclusion. This value correlates with the published data for the diffusion coefficients of other dyes in the skin dermis and the pathologically changed mucosa of the maxillary sinus of a volunteer. The results can be used for the development of modern methods in medicine, combining diagnostic and therapeutic technologies, which are now known under the general name – theranostics, as well as clinicians to develop sound protocols for photodynamic therapy, eliminating the trauma due to laser effects
Keywords: 
effective diffusion coefficient, Rivanol, human buccal mucosa, diffuse reflectance spectrum

Список литературы: 
  1. Sazonova N.V. Projavlenija vospalenija parodonta pri razlichnyh somaticheskih zabolevanijah. Obrazovanie i nauka v Rossii i za rubezhom. 2019; 3 (51): 71–6. [Sazonova N. V. Manifestations of inflammation of the parodentium with different somatic diseases. Education and science in Russia and abroad. 2019; 3 (51): 71–6 (in Russian)]
  2. Eaton K., Ower P. Practical Periodontics. L.: Churchill Livingstone; 2015; 376.
  3. Borovskij F.V., Mashkillejson A.L.. Hronicheskij retsidivirujuschij aftoznyj stomatit. Zabolevanija slizistoj obolochki polosti rta i gub. M.: Medpress, 2011; 325. [Borovsky FV, Mashkilleyson AL. Chronic recurrent aphthous stomatitis. Diseases of the mucous membranes of the mouth and lips. M.: Medpress, 2011; 325 (in Russian)]
  4. Gazhva S.I., Kotunova N.A., Kulikov A.S. Primenenie fotodinamicheskoj terapii v algoritme lechenija erozivno-jazvennoj formy krasnogo ploskogo lishaja slizistoj obolochki rta. Sovremennye problemy nauki i obrazovanija. 2018; 4: 13–5. [Gazhva S.I., Kotunova N.A., Kulikov A.S. The use of photodynamic therapy in the treatment of erosive-ulcerative forms of lichen planus of the oral mucosa. Modern problems of science and education. 2018; 4: 13–5 (in Russian)]
  5. Orehova L.Ju., Pushkarev O.A., Lukavenko A.A. Fotodinamicheskaja terapija v klinike terapevticheskoj stomatologii. Innovatsionnaja stomatologija. 2010; 1: 24–9. [Orekhova L.Yu., Pushkarev OA, Lukavenko A.A. Photodynamic therapy in the clinic of therapeutic dentistry. Innovative dentistry. 2010; 1: 24–9 (in Russian)]
  6. Tuchin V.V. Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnostics, 3rd edition, Bellingham, WA: SPIE Press, 2015; 866.
  7. Popova A.E., Kriheli N.I. Izmenenie mikrobiologicheskih i biohimicheskih pokazatelej u patsientov s hronicheskim generalizovannym parodontitom srednej stepeni posle vkljuchenija fotodinamicheskoj terapii v plan kompleksnogo lechenii. Rossijskaja stomatologija. 2013; 6 (4): 4–11. [Popova A.E., Krikheli N.I. Changes in microbiological and biochemical parameters in patients with moderate chronic generalized periodontitis after the inclusion of photodynamic therapy in the complex treatment plan. Russian dentistry. 2013; 6 (4): 4–11 (in Russian)]
  8. Chikina E.S. Fotodinamicheskaja terapija ostryh i hronicheskih verhnecheljustnyh sinusitov. Dis. … kand. med. nauk. Saratov, 2005; 388. [Chikina E.S. Photodynamic therapy of acute and chronic maxillary sinusitis. Dis. ... Candidate of Medical Sciences. Saratov, 2005; 388 (in Russian)]
  9. Tuchina E.S. Tuchin V.V., Jaroslavskij I.V., Al'tshuler G.B. Fotodinamicheskoe vozdejstvie krasnogo (625 nm) i izluchenij na bakterii vida Propioni bacterium acnes, obrabotannye fotosensibilizatorami. Izvestija Saratovskogo universiteta. Serija: Fizika. 2008; 12 (1): 21–6. [Tuchina E.S. Tuchin V.V., Yaroslavsky I.V., Altshuler G.B. Photodynamic effects of red (625 nm) and radiation on bacteria of the species Propioni bacterium acnes, treated with photosensitizers. News of the Saratov University. Series: Physics. 2008; 12 (1): 21–6 (in Russian)]
  10. Tuchina E.S., Tuchin V.V., Khlebtsov B.N., Khlebtsov N.G. Phototoxic effect of conjugates of plasmon-resonance nanoparticles with indocyanine green dye on Staphylococcus aureus induced by IR laser radiation. Quantum Electronics. 2011; 41 (4): 354–9.
  11. Engel E., Schraml R., Maisch T., Kobuch K., Konig B., Szeimies R.M., Hillenkamp J., Baumler W. Vasold R. Light Induced Decomposition of Indocyanine Green. Invest. Ophthalmol. Vis. Sci. 2008; 49 (5): 1777–83.
  12. Xu R.X., Huang J., Xu J.S., Sun D., Hinkle G.H., Martin E.W., Povoski S.P. Fabrication of indocyanine green encapsulated biodegradable microbubbles for structural and functional imaging of cancer. J. Biomed. Opt. 2009; 14 (3): 034020–6.
  13. Egorova A.V., Brill' G.E., Bugaeva I.O., Tuchina E.S., Nechaeva O.V. Fotodinamicheskoe vozdejstvie lazernogo izluchenija krasnoj oblasti spektra na rost shtammov Staphylococcus aureus s ispol'zovaniem fotoditazina. Izvestija Saratovskogo universiteta. Serija: Himija. Biologija. Ekologija. 2017; 17 (4): 428–31. [Egorova A.V., Brill G.E., Bugaeva I.O., Tuchina E.S., Nechaeva O.V. Photodynamic effect of laser radiation in the red region of the spectrum on the growth of Staphylococcus aureus strains using photoditazine. News of the Saratov University. Series: Chemistry. Biology. Ecology. 2017; 17 (4): 428–31 (in Russian)]
  14. Amelink A., Kaspers O.P., Sterenborg H.J.C.M., van der Wal J.E., Roodenburg J.L.N., Witjes M.J.H.. Non-invasive measurement of the morphology and physiology of oral mucosa by use of optical spectroscopy. Oral Oncology. 2008; 44: 65–71.
  15. https://omlc.org/spectra/water/ (Data obraschenija 02.04.2019)
  16. Kotyk A., Janachek K. Membrannyj transport. M.: Mir, 1980; 344. [Kotyk A., Janacek K. Membrane transport. M.: Mir, 1980; 344 (in Russian)]
  17. https://omlc.org/spectra/hemoglobin/summary.html (Data obraschenija 02.04.2019)
  18. Kozyreva O.D., Pushkareva A.E., Shalobaev E.V., Biro I. Issledovanie vlijanija stepeni oksigenatsii krovi na signal obratnogo rassejanija izluchenija pri pomoschi chislennogo modelirovanija. Nauchno-tehnicheskij vestnik informatsionnyh tehnologij, mehaniki i optiki. 2015; 15 (1): 163–5. [Kozyreva OD, Pushkareva AE, Shalobaev EV, Biro I. Investigation of the influence of the degree of blood oxygenation on the radiation backscatter signal using numerical simulation. Scientific and Technical J. of Information Technologies, Mechanics and Optics. 2015; 15 (1): 163–5 (in Russian)]
  19. Genina E.A., Bashkatov A.N., Tuchin V.V. Study of diffusion of indocyanine green as a photodynamic dye into skin using backscattering spectroscopy. Quantum Electronics. 2014; 44 (7): 689–95.