Addressed delivery of valproic acid to target cells in treatment of epilepsy using aptamers

The aim of the research. To develop a drug based on aptamers that cross the blood-brain barrier, targeting the delivery of valproic acid to the brain. Material and methods. We used the Brain 1 and Co 451 aptamers passing through the blood-brain barrier, obtained using the in vivo-SELEX technology, the affi nity of which was determined using fl ow cytometry fl uorescence microscopy. Th e drug for targeted delivery of valproic acid was obtained using the conjugation of Konvulex, biotinylated aptamers, and streptavidin protein. Th e antiepileptic effi cacy of the drug was evaluated in ICR mice with a lithium-pilocarpine model of the development of epilepsy. Aft er the injection of pilocarpine, the animals were monitored using round-the-clock video recording. For the treatment of epilepsy, a valproic acid dose of 130 μg / g of animal weight was used. During treatment with a drug for targeted delivery, the dose of valproic acid was reduced to 5 μg / g. Evaluation of status epilepticus in mice was performed using the Racine Scale. Results. In animals, using the lithium-pilocarpine model, status epilepticus was formed at diff erent stages - from the 1st to the 5th. In all groups of animals, complete overcoming of status epilepticus did not occur in 120 min. In the group of mice treated with valroic acid, no change in their status occurred within 80 minutes. When mice were treated with conjugates based on the Brain 1 and Co 451 aptamers, the blockade of status epilepticus in mice, despite the lower (26 times) doses of the administered antiepileptic drug, occurred faster. Conclusion. A scientifi c platform has been developed for the development of drugs for targeted delivery of antiepileptic drugs with high effi ciency and low toxicity