Background:

   Neurogenesis must be continuous and dynamic throughout each individual's life so that the efficiency of different brain parts does not become weak and ineffective. On the other hand, protecting old neurons can also be a solution, so synthetic substances simultaneously having both protective and neurogenic functions can be a good option for targeted drug delivery in brain diseases and aging. In particular, agmatine has a beneficial role in protecting and neurogenic roles due to its role as a polyamine precursor and its ability to cross the blood-brain barrier while inhibiting nitric oxide synthase, and previous studies have also reported a protective and neurogenic role. Therefore, this study aimed to target drug delivery with nanoliposomes and investigate its effects on the proliferation and differentiation of neural stem cells.

  Materials and methods 

  In this experimental-in vitro study, neural stem cells were first isolated from the subventricular zone of the adult mouse brain and proliferated and neurospheres were formed in the presence of epidermal growth factor and fibroblast growth factor. Cell viability was measured in six groups including the control group, a nanoliposome group, an agmatine group with concentrations of (25 and 50) micromolar, and nanoliposome groups treated with agmatine with concentrations of (25 and 50) micromolar by the MTT method. Also, the number of neurospheres, the number of cells resulting from each neurosphere, and the number of neuronal and glial cells following differentiation were counted. The collected data were analyzed using a one-way variance test.  Result:   The cell survival of neural stem cells in the agmatine groups increased in a dose-dependent manner, with a significant increase in the 50 and 100 μM groups compared to the 10 μM agmatine group (**p<0.01). The mean number of neurospheres in the nanoliposome-agmatine 50 μM groups showed a significant increase compared to the liposome and control groups (*p<0.05, **p<0.01). The mean number of neuronal cells in the nanoliposome-agmatine 25 and 50 groups showed a significant increase compared to the liposome and control groups (***p<0.0001).  Conclusion:  The data from this study showed that treatment with agmatine and nano-liposomes containing agmatine can be effective in the proliferation and differentiation of stem cells, and that this increase in proliferation and differentiation in the targeted method with liposomes was effective at a lower concentration of agmatine, which may indicate the targeting of the liposomal system and its value.