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

• Published in: Bulletin of experimental biology and medicine 2017-12, Vol.164 (2), p.285-292
• Main Authors: Baklaushev, V. P., Yusubalieva, G. M., Burenkov, M. S., Mel’nikov, P. A., Bozhko, E. A., Mentyukov, G. A., Lavrent’eva, L. S., Sokolov, M. A., Chekhonin, V. P.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Blood; Blood proteins; Brain; Cell Biology; Central nervous system; Cerebrospinal fluid; Confocal microscopy; Cortex (frontal); Cortex (olfactory); Fluorescence; Internal Medicine; Intranasal administration; Laboratory Medicine; Molecular weight; Neurons; Nose; Olfactory bulb; Pathology; Permeability; Plasma proteins; Protein binding; Proteins; Rodents; Tracers (Biology)
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-017-3974-9

Permeability of the blood—brain barrier for protein fractions 50-100 kDa (PF 50–100 ) 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 PF 50–100 -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 PF 50–100 -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 PF 50–100 -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 PF 50–100 -FITC in the olfactory cortex and frontal cortex neurons with functionally active nuclei was observed in 6, 12 and 24 h after intranasal administration.