Polymeric nanoparticles as drug delivery tools for brain degenerative disorders: In vitro assessment and drug release properties

Therapies for neurodegenerative disease are limited in efficacy and tolerability, largely due to poor drug penetration across the BBB and off-target effects. Polymeric nanoparticles (NPs) are advantageous for brain drug delivery due to their safety profiles, drug-loading capacity, controlled-release properties and potential for drug repurposing. The aim of this work was to perform in vitro screening of NPs synthesised using the FDA-approved poly(lactic co-glycolic acid) (PLGA) polymer as drug delivery vehicles in primary rat neurons and glia as a prerequisite for further assessment in animal models of neurodegenerative disorders. NPs were synthesised using a PLGA-polyethylene glycol (PEG) copolymer. PLGA-PEG NPs were characterised, applied to primary rat neurons or glia and biocompatibility was assessed through morphological analysis. PLGA-PEG were loaded with anti-inflammatory drug Formoterol, drug release was investigated, and Formoterol-PLGA-PEG were applied to glia stimulated by interferon (IFN). PCR was performed to quantify the expression of pro-inflammatory molecules by glia exposed to IFN and Formoterol-PLGA-PEG. The resulting conditioned media (CM) was transferred to neurons for assessment of viability and complexity. PLGA-PEG NPs did not affect neuronal viability, complexity or cause glial reactivity. PLGA-PEG NPs were loaded with and released formoterol over 24 hours. Formoterol-PLGA-PEG NPs reduced inflammatory cytokine expression in IFN-stimulated glia and attenuated the reduction in neuronal complexity associated with IFN CM. Therefore, PLGA-PEG are compatible with primary neurons and glia in vitro. The ability of Formoterol-PLGA-PEG NPs to release drug and reduce inflammation in vitro, makes them promising candidates for in vivo screening in preclinical models of neurodegenerative disease.