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Bioluminescent Study of the Distribution of High-Molecular-Weight Protein Fraction of Cellex Daily Preparation in the Brain after Intranasal Administation

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Permeability of the blood—brain barrier for protein fractions 50-100 kDa (PF50–100) of Cellex Daily preparation labeled with fluorescent tracer FITC and non-conjugated FITC were compared after intranasal administration of the preparations to healthy rats. Fluorimetrical analysis of the serum and cerebrospinal fluid samples showed that Cellex Daily PF50–100-FITC administered intranasally penetrated into the blood and cerebrospinal fluid with maximum accumulation in 2 h after administration and persists in the circulation for 24 h probably due to binding with plasma proteins. The differences in the kinetic profile of PF50–100-FITC and free FITC indirectly suggest that the major part of the preparation is not degraded within 24 h and FITC is probably not cleaved from the protein components of the preparation. In vivo fluorescence analysis showed significant fluorescent signal in the olfactory bulbs in 6 h after intranasal administration; hence, the preparation administered via this route can bypass the blood—brain barrier. Scanning laser confocal microscopy of rat brain sections confirmed penetration of the high-molecular weight protein fraction PF50–100-FITC into CNS structures. The most pronounced accumulation of the labeled drug was observed in the olfactory bulb in 6 and 12 h after administration. In contrast to free FITC administered in the control group, significant accumulation of PF50–100-FITC in the olfactory cortex and frontal cortex neurons with functionally active nuclei was observed in 6, 12 and 24 h after intranasal administration.

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Authors and Affiliations

  1. Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, Federal Medical-Biological Agency, Moscow, Russia

    V. P. Baklaushev & P. A. Mel’nikov

  2. V. P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, Russia

    G. M. Yusubalieva, P. A. Mel’nikov & V. P. Chekhonin

  3. Farm-Sintez Company, Moscow, Russia

    M. S. Burenkov, E. A. Bozhko, G. A. Mentyukov, L. S. Lavrent’eva & M. A. Sokolov

  4. N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia

    V. P. Chekhonin

Authors
  1. V. P. Baklaushev
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  2. G. M. Yusubalieva
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  3. M. S. Burenkov
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  4. P. A. Mel’nikov
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  5. E. A. Bozhko
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  6. G. A. Mentyukov
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  7. L. S. Lavrent’eva
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  8. M. A. Sokolov
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  9. V. P. Chekhonin
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Correspondence to V. P. Baklaushev.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 196-204, July, 2017

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Baklaushev, V.P., Yusubalieva, G.M., Burenkov, M.S. et al. Bioluminescent Study of the Distribution of High-Molecular-Weight Protein Fraction of Cellex Daily Preparation in the Brain after Intranasal Administation. Bull Exp Biol Med 164, 285–292 (2017). https://doi.org/10.1007/s10517-017-3974-9

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  • DOI: https://doi.org/10.1007/s10517-017-3974-9

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