(G-265) Nanoparticle physicochemical properties impact their association, internalization, and trafficking in sensory neurons

Introduction:: Polymeric nanoparticles (NPs) have the potential to act as easily tunable drug delivery vehicles in many nerve-related conditions. In particular, chronic pain, which involves sensitization of nociceptors, is a potential application for neuro-targeting NPs. However, in order to optimize and tailor drug delivery, it is necessary to fully characterize the interactions between nanoparticles and neurons and to elucidate the relationship between NP characteristics and in vivo performance.



In this work, we systematically examine the effects of NP size, surface charge, and surface chemistry in terms of their effect on the association, internalization, and trafficking within sensory-phenotype neurons.


Materials and Methods:: A library of self-assembled core-shell polymeric nanoparticles with amphiphilic block co-polymers polyethylene glycol-b-poly lactic acid (PEG-PLA), poly-2-ethyl-2oxazoline-b-poly lactic acid (P2OX-PLA), and poly-hydroxy-ethyl-methacrylate)-b-poly lactic acid (PHEMA-PLA) were synthesized using Flash Nanoprecipitation (FNP). Fluorophore-loaded NPs were used to examine rates of association, internalization, and intracellular trafficking within immortalized dorsal root ganglia (F11) using confocal microscopy. Co-staining with early endosomes was used to determine rates of endocytosis.

Results, Conclusions, and Discussions:: Results: PEGylated, P2OXylated, and PHEMAylated NPs demonstrated predictable and controllable size formation from 50nm to 250nm with low polydispersity. We were also successful in fine tuning nanoparticle zeta potential by doping the NP surface with carboxylate-terminated PEG. F11 cells were successfully differentiated into sensory neuron phenotype.

Preliminary results show size dependent differences in uptake rate as well as significant differences between PEGylated and P2OXylated association in vitro.



Discussion and Conclusion: Here, we present the first use of P2OX and PHEMA as surfaces with FNP. Nanoparticle surface chemistry, zeta potential, and size affect nano-neuronal interactions. These findings can be used to optimize spatial and temporal drug action at sensory nerves. In particular, drug release within the endosomes of sensory neurons has the potential to improve anti-nociception for GPCR-mediated pain pathways. In addition, the potential to identify and target hyperexcitable sensory neurons for treatment of neuropathic allodynia remains an important goal.


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