Study of the possibility of using metformin by intranasal administration for the correction of behavioral and cognitive dysfunctions of rats

Relevance . Metformin is an antidiabetic agent in the therapy of type 2 diabetes mellitus, which has a complex of pharmacological effects that may allow its use as a geroprotector and a means for the treatment of cognitive and behavioral disorders. Metformin when administered orally has low bioavailability (50–60 %), as well as the risk of side effects, which is the rationale for studying the intranasal route of administration of metformin. Objective . To investigate the behavioral effects of metformin during intranasal administration as a rationale for the development of its intranasal dosage form. Materials and methods . The object of the study was metformin administered intranasally (i/n) to rats at a dose of 70 mg/kg. The intragastric (i/g) route of administration (70 mg/kg) was used for comparison. After 30-day i/n and i/g administration of metformin, the rats were subjected to behavioral tests: the T-Maze test, Water Maze test, Elevated Plus-Maze test (EPM), and Extrapolation Escape task (EE). The Student's t-test in Graph pad Prism 8.0.1 program was used for statistical processing. Results . When administered i/n, there was 5.6 times ( p = 0.022) decrease in the latent period of arm selection ( p = 0.022), and when administered i/g, there was 2.9 times ( p = 0.01) decrease in the “T-maze”test compared to the control. No statistically significant result was found in the “EPM”test when applied i/n, in contrast to i/g, in which the duration of stay of rats in the OА of the maze was 3.0 times ( p = 0.01) more than the control, and in the CA — 1.3 times ( p = 0.01) less. In the “EE” test, i/n administration of metformin contributed to 5.1 times ( p = 0.02) decrease in jump duration compared to control. In case of i/g administration metformin, the duration of the jumping period was 2.9 times shorter ( p = 0.038). Conclusion . Intranasal administration of metformin can be considered as an alternative way of its use and be the basis for the development of a system of directed delivery of metformin.