Polymeric nanoparticles as a platform for nose-to-brain delivery

The treatment of brain disorders <i>via</i> nose-to-brain delivery (NtBD) is a promising non-invasive strategy to bypass the blood-brain barrier. In this study, we developed and characterized polymeric nanoparticles (NPs) based on polylactic acid (PLA) and poloxamers (P188 and P407), synthesized <i>via</i> one-step or two-step nanoprecipitation methods. All formulations resulted in homogeneous, negatively charged NPs with a diameter of 110 nm, compatible with efficient brain delivery. Dissipative particle dynamics simulations confirmed the structural organisation of NPs and highlighted the role of poloxamers in forming a hydrophilic surface. NPs modified with poloxamers demonstrated improved colloidal stability in artificial mucus and cerebrospinal fluid, unlike bare PLA NPs. <i>In vitro</i> assays on human nasal epithelial cells and differentiated neuronal cells showed no cytotoxicity and cellular uptake in both cell types. <i>In vivo</i> fluorescence imaging and immunostaining revealed the presence of NPs in the olfactory bulb as early as one hour post-administration. These results support NP-PLA-P188 as a promising formulation for effective and safe NtBD of drugs targeting neurological diseases.