A NIR labelled PLGA-PEG/PHEA-g-Dy700-g-PLA self-traceable nanoplatform for intranasal delivery

In the present work, near infrared (NIR) fluorescent polymeric nanoparticles were developed as a traceable platform to investigate their path following intranasal administration. Nanoparticles were produced by a nanoprecipitation method using blends of polyethylene glycol–polylactic acid-co-glycolic acid (PLGA–PEG) and an amphiphilic graft copolymer, α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide-g-Dy700-g-polylactide (PHEA-g-Dy700-g-PLA), in which the NIR fluorophore Dy700 was covalently bound to ensure signal stability. Physicochemical analyses using dynamic light scattering (DLS) and atomic force microscopy (AFM) demonstrated that all nanoparticle formulations exhibited appropriate colloidal properties for intranasal administration (a mean size of <130 nm, a polydispersity index of <0.3, and ζ-potential ranging from −25 mV to −1 mV) and a spherical shape. Quantitative 1H-NMR confirmed the surface PEGylation of the nanoparticles, supporting their potential mucus-penetrating behaviour. The nanoparticles maintained their physicochemical properties after incubation in simulated biological fluids for up to three hours. In vitro studies on olfactory ensheathing cells (OECs) demonstrated cytocompatibility and efficient cellular uptake. Pareto analysis and a desirability function were applied by considering both normalized cellular uptake and a fluorescence signal as response variables, in order to identify the most suitable formulation for fluorescence molecular tomography (FMT) and subsequent in vivo evaluation. Following intranasal administration in healthy mice, FMT enabled non-invasive, three-dimensional monitoring of nanoparticle distribution, revealing rapid and preferential accumulation of fluorescence signals within the brain region.