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

Abstract The effective delivery and ‘neuroavailability’ of central nervous system (CNS) bioactives such as dopamine is crucial for successful treatment of Parkinson’s disease (PD) symptoms. Although much dopamine (DA) (neurotransmitter) therapy that manage the symptoms of PD have proved promising, the poor physicochemical properties including pharmacokinetic profiles impede diffusing across the Blood–Brain Barrier (BBB), severe side effects, short half-life and poor bioavailability. Therefore, the aim of this study was to advance the progress made thus far by delivering DA within polydopamine nanoparticles (NPs) that were rendered more biomimetic to neurons via a novel palmitic acid (PA) coating to achieve maximum uptake in A172 brain cells and capable of crossing the BBB. A modified one-pot method was used to prepare the PDA NPs for dopamine loading. Particle size analysis revealed a size distribution within 130–160 nm capable of traversing cells of the BBB with a stable zeta potential (surface charge) within −14 mV–18 mV, (PDI = 0.236–0.314). NMR and FTIR molecular studies proved the successful surface-coating of the PDA NPs with PA and physicochemical analyses demonstrated an amorphous nanostructure for the DA-loaded PDA NPs. The PA coating shifted to a more crystalline form (2 θ , 7–9 (°)) improving the pharmaceutical stability. The encapsulation efficiency of DA was maximised using a modified nanoprecipitation technique resulting in higher loading efficiency (97% and 99%) for DA and PA-coated NPs respectively. The in vitro DA release study showed an initial rapid release phase followed by controlled release over 24 h for the PA-coated PDA NPs. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) demonstrated excellent viability of the NPs against the cells with minimal toxicity observed was consistent with cell morphology investigations that confirmed no damage, rupture, or reorganization of cellular morphology or shape. Cell uptake studies in A172 cells revealed the biomimetic features of the PDA NPs conferred by the novel PA-coating with preferential uptake and accumulation of PDA NPs in the nucleus especially with the PDA coated NPs. Considering the attributes of this novel nano-formulation approach, it also presents the potential to design an intranasal formulation of DA for minimally invasive nose-to-brain delivery of DA capable of BBB diffusion and neuron targeting in PD affected brain tissue.