Microfluidic development of brain-derived neurotrophic factor loaded solid lipid nanoparticles: An in vitro evaluation in the post-traumatic brain injury neuroinflammation model
Federica Sommonte, Ilaria Arduino, Rosa Maria Iacobazzi, Luna Laera, Teresa Silvestri, Angela Lopedota, Alessandra Castegna, Nunzio Denora
Abstract
Microfluidic-based nanoscale drug delivery systems have risen to prominence in the field of precision nanomedicine in recent years. This intriguing innovation could provide unique therapeutic prospects in the treatment of serious disorders as traumatic brain injury, a potentially fatal condition that is widespread during childhood. According to current scientific study, neurotrophins are vital for the healing of injured brain parenchyma, and the brain-derived neurotrophic factor (BDNF) in particular may have significant regenerative effects. To address BDNF-related pharmacokinetic constraints, microfluidic-assisted manufacturing of BDNF-loaded solid lipid nanoparticles (BDNF-SLNs) was carried out, and following evaluation, the formulation demonstrated optimum characteristics in terms of size (190.3 ± 10.1 nm), PDI (0.180 ± 0.023), and ζ-potential (– 39.2 ± 1.30 mV). Short-term stability studies and the haemolysis assay verified the formulation's biocompatibility, while an in vitro permeability analysis revealed an increase in the Papp of the encapsulated BDNF (1.27x10-5 cm/sec) as compared to plain BDNF (9.31x10-6 cm/sec). The in vitro mimicked neuroinflammatory model demonstrated an enhanced decrease in nitrite production and Nos mRNA levels using BDNF-SLNs compared to plain BDNF as a control, validating the proficiency of the microfluidic-based drug delivery systems as pioneering and valuable approaches for the brain delivery of biologicals.