Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain

Trimethylated chitosan (TMC) surface-modified poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (TMC/PLGA–NP) were synthesized as a drug carrier for brain delivery. TMC was covalently coupled to the surface of PLGA nanoparticles (PLGA–NP) via a carbodiimide-mediated link. The zeta potential of TMC/PLGA–NP was about 20 mV with a mean diameter around 150 nm. 6-coumarin loaded PLGA–NP and TMC/PLGA–NP were injected into the caudal vein of mice, and fluorescent microscopy of brain sections showed a higher accumulation of TMC/PLGA–NP in the cortex, paracoele, the third ventricle and choroid plexus epithelium, while no brain uptake of PLGA–NP was observed. There was no pronounced difference in cell viability between TMC/PLGA–NP and PLGA–NP as shown by MTT assay. Behavioral testing showed that the injection of coenzyme Q10 loaded TMC/PLGA–NP greatly improved memory impairment, restoring it to a normal level, but the efficacy was slight for loaded PLGA–NP, without TMC conjugation. The senile plaque and biochemical parameter tests confirmed the brain-targeted effects of TMC/PLGA–NP. These experiments show that TMC surface-modified nanoparticles are able to cross the blood–brain barrier and appear to be a promising brain drug delivery carrier with low toxicity.