In vitro and in vivo characterization of human serum albumin-based PEGylated nanoparticles for BDNF and NT3 codelivery

The utilization of neurotrophins in medicine shows significant potential for addressing neurodegenerative conditions, such as age -related macular degeneration (AMD). However, the therapeutic use of neurotrophins has been restricted due to their short half-life. Here, we aimed to synthesize PEGylated nanoparticles based on electrostatic -driven interactions between human serum albumin (HSA), a carrier for adsorption; neurotrophin-3 (NT3); and brain -derived neurotrophic factor (BDNF). Electrophoretic (ELS) and multi -angle dynamic light scattering (MADLS) revealed that the PEGylated HSA-NT3-BDNF nanoparticles ranged from 10 to 430 nm in diameter and exhibited a low polydispersity index ( <0.4) and a zeta potential of -8 mV. Based on microscale thermophoresis (MST), the estimated dissociation constant (K d ) from the HSA molecule of BDNF was 1.6 mu M, and the K d of NT3 was 732 mu M. The nanoparticles were nontoxic toward ARPE-19 and L-929 cells in vitro and efficiently delivered BDNF and NT3. Based on the biodistribution of neurotrophins after intravitreal injection into BALB/c mice, both nanoparticles were gradually released in the mouse vitreous body within 28 days. PEGylated HSA-NT3-BDNF nanoparticles stabilize neurotrophins and maintain this characteristic in vivo . Thus, given the simplicity of the system, the nanoparticles may enhance the treatment of a variety of neurological disorders in the future.