Bioavailability Study of Recombinant Plasmid DNA Nerve Growth Factor after Intramuscular Injection by Electroporation

Viktor V. Shilov; Mikhail A. Yudin; Nikolai G. Vengerovich; Taras V. Shcherbakov; Aleksandra S. Bogacheva

doi:10.21638/spbu11.2019.201

Авторы

Viktor V. Shilov North-Western State Medical University named after I. I. Mechnikov, 47, Piskarevskii pr., St. Petersburg, 195067, Russian Federation;North-West Public Health Research Center Rights Protection and Human Wellbeing, 4, 2-ya Sovetskaya ul., 191036, St. Petersburg, Russian Federation
Mikhail A. Yudin North-Western State Medical University named after I. I. Mechnikov, 47, Piskarevskii pr., St. Petersburg, 195067, Russian Federation;Federal State Budgetary Institution “State Research Testing Institute of Military Medicine” of the Ministry of Defense of Russian Federation, 4, Lesoparkovaya ul., St. Petersburg, 195043, Russian Federation
Nikolai G. Vengerovich Saint Petersburg State Chemical Pharmaceutical Academy (SPCPA), 14a, ul. Professora Popova, St. Petersburg, 197376, Russian Federation ; Federal State Budgetary Institution “State Research Testing Institute of Military Medicine” of the Ministry of Defense of Russian Federation, 4, Lesoparkovaya ul., St. Petersburg, 195043, Russian Federation
Taras V. Shcherbakov North-West Public Health Research Center Rights Protection and Human Wellbeing, 4, 2-ya Sovetskaya ul., 191036, St. Petersburg, Russian Federation
Aleksandra S. Bogacheva North-Western State Medical University named after I. I. Mechnikov, 47, Piskarevskii pr., St. Petersburg, 195067, Russian Federation

DOI:

https://doi.org/10.21638/spbu11.2019.201

Аннотация

Comparative analysis of plasmid DNA delivery into cells efficiency (with effective agent concentration 250 μg/kg), ensuring accumulation of nerve growth factor (NGF) after intramuscular injection and intramuscular administration using electroporation method on rats was performed. Application of electroporation method ensured over 4 times increase of DNA plasmid concentration in muscle tissue within the first hour after its injection and increased the duration of its determination. Higher bioavailability parameters were confirmed by 3 times increase in gene expression level, encoding NGF accumulation and 3 times increase in concentration of the target NGF protein in blood plasma. The results obtained allow us to recommend this method for introduction of NGF plDNA in its biological activity and effectiveness in models of nerve damage investigation.

Ключевые слова:

plasmid DNA, pharmacokinetics, gene expression, bioavailability, electroporation

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