Biomimetic palmitic acid functionalized polydopamine nanoparticles for targeted CNS delivery of the neurotransmitter dopamine in A172 neuronal cells

The effective delivery and ‘neuroavailability’ of CNS bioactives such as dopamine (DA) is crucial to successfully treat of Parkinson’s disease (PD) symptoms. However, DA as a neurotransmitter has poor solubility and an erratic pharmacokinetic profile impeding diffusing across the Blood–Brain Barrier (BBB). Therefore, the aim of this study was to enhance the CNS delivery of DA using biomimetic polydopamine nanoparticles (PDA-NPs) using a novel palmitic acid (PA) coating to achieve maximum uptake demonstrated in A172 neuronal cells. A modified one-pot method was used to prepare the DA-loaded PDA-NPs. Particle size analysis revealed 130 – 160 nm particles with a stable surface charge of between -14 mV – 18 mV, (PDI = 0.236 – 0.314). NMR and FTIR molecular studies proved the successful synthesis of PDA-NPs and subsequently PA shifted the nanosystem to a more crystalline form (2ɵ, 6 – 10 (°)) with improved pharmaceutical stability. The DA encapsulation efficiency was maximised using a modified nanoprecipitation technique resulting in higher loading efficiency (97%). The in vitro DA release showed an initial rapid release phase followed by controlled release over 24 hours for the PA-coated PDA-NPs. A MTT assay demonstrated cell viability of the nanosystem against A172 cells, consistent with the consistent cell morphology. In addition, uptake in A172 cells revealed the biomimetic features of the PDA-NPs conferred by the novel PA-coating with preferential accumulation. Considering the attributes of this novel nanosystem, it presents as a promising prototype for intranasal formulation to deliver DA as a nose-to-brain delivery strategy targeting brain tissue in PD.