STUDY OF THE POSSIBILITY OF ENHANCING THE EFFICIENCY OF ERYTHROCYTE LOADING WITH TERPENE-INDOLE ALKALOIDS

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DOI: https://doi.org/10.29296/25419218-2018-07-06
Issue: 
7
Year: 
2018

O.V. Trineeva, A.D. Khalakhakun, A.I. Slivkin Voronezh State University; 1, Universtitetskaya Sq., Voronezh 394006, Russian Federation

Introduction. One of the main directions in the development of modern oncology pharmacy is to design more advanced formulations of known biologically active substances for their effective delivery to the target cells. The terpene-indole alkaloids (TIAs) vincristine (VCR) and vinblastine (VBL) effectively inhibit the proliferation of tumor cells, but have no selective effect, by affecting both infected and healthy cells. The aforementioned problems can be comprehensively solved via targeted transport. Objective: to investigate the possibilities of enhancing the loading efficiency of anticancer agents derived from Madagascar periwinkle (Catharanthus roseus) (VCR and VBL) when preparing immobilized cell formulations of these drugs. Material and methods. The modified formulations of VCR and VBL were obtained through their inclusion in the erythrocyte carriers, by using the modified hypoosmotic lysis method. The loading of erythrocytes with TIA was also carried out in the incubation medium containing the modifying agents: the aprotic solvent – dimethyl sulfoxide (DMSO), polyethylene glycols (PEG-4000 and PEG-400), and adenosine triphosphate (ATP). For the detection and quantitative determination of VCR and VBL, the UV-spectral characteristics of these drugs and spectrophotometric methods were used. TIAs were isolated from the erythrocyte carriers by means of gel chromatography. Results. Osmotic pressure was substantially increased in the PEG-4000- and PEG-400-modified media compared to the non-modified medium. The efficiency of inclusion in the freshly isolated red blood cells averaged 42.963% for VCR and 44.266% for VBL. The modified media showed the high loading efficiency of TIAs: VCR (65.699%) and VBL (55,857%) in the PEG medium; VCR (61.071%) and VBL (62.425%) in the DMSO medium; VCR (49.608%) and VBL (49.228%) in the ATP medium. Conclusion. Modification of the incubation medium while preparing of the erythrocyte forms of TIAs by hypoosmotic lysis leads to the higher loading efficiency of VCR and VBL. The highest (10-20% increase) efficiency of TIA loading into the red blood cells was seen in the PEG- and DMSO-modified media.
Keywords: 
targeted drug transport
vincristine
vinblastine
erythrocyte carriers
inclusion efficiency
modified media
References: 
  1. Zaborovskiy A.V., Gurevich K.G. Modelirovanie napravlennogo transporta lekarstvennyh veshhestv. Chast` I. Odnokratnoe vedenie. Sibirskiy onkologicheskiy zhurnal, 2017; 16 (1): 59–65. DOI: 10.21294/1814-4861-2017-16-1-59-65
  2. Zaborovskiy, A.V., Gurevich K.G. Modelirovanie napravlennogo transporta lekarstvennyh veshhestv. Chast` II. Mnogokratnoe vvedenie. Sibirskiy onkologicheskiy zhurnal, 2017; 16 (2): 36–41. DOI: 10.21294/1814-4861-2017-16-2-36-41
  3. Trineeva O.V., Halahakun A.D., Slivkin A.I., Chupandina E.E. Morfologicheskie i fiziko-himicheskie svoystva e`ritrocitarnyh nositeley, inkapsulirovannyh terpeno-indol`nymi alkaloidami. Razrabotka i registraciya lekarstvennyh sredstv, 2018;1: 40–4.
  4. Ó’Fágáin C., Cummins P.M., O’Connor B.F. Gel-Filtration Chromatography. Protein Chromatography Methodsand Protocols: Methods in Molecular Biology (ed. D. Walls, S.T. Loughran). Totowa, NJ: Humana Press, 2011; 25–33. DOI https://doi.org/10.1007/978-1-60761-913-0_2
  5. Nikolayenko I.V. et al. Preparation of highly purified human IgG, IgM and IgA for immunization and immunoanalysis. Ukrainica Bioorganica Acta, 2005; 2: 3–11.
  6. Stratton F., Smith D.S., Rawlinson V.I. Value of gel filtration on Sephadex G-200 in the analysis of blood group antibodies. Journal of Clinical Pathology, 1968; 21(6): 708–14.
  7. Lopuhov L.V. i dr. Hromatograficheskie metody ochistki belkov. Kazan`: KFU, 2013; 1–48.