(78g) Investigating Nanoparticle-Neuron Interactions with Peg-Alternative Surfaces for Enhanced Pain Drug Delivery

Polymeric nanoparticles (NPs) are versatile and tunable drug delivery vehicles. However, barriers to clinical translation remain due to gaps in understanding how NP characteristics impact in vivo performance. In particular, the use of nanoparticles with peripheral neurons has not been extensively studied. It is necessary to fully characterize the interactions between nanoparticles and neurons for potential applications in burdensome conditions such as chronic and neuropathic pain.

The goal of this work is to explore the use of PEG alternatives for NP surfaces and examine the effects of NP physicochemical characteristics on sensory neuronal membrane association, rate of internalization, and intracellular trafficking. To do this, a library of self-assembled core-shell polymeric nanoparticles with surfaces polyethylene glycol (PEG), poly-2-ethyl-2oxazoline (P2OX), “randomized” poly(ethylene oxide)-co-(glycidyl methyl ether) (rPEG) and poly-hydroxy-ethyl-methacrylate) (PHEMA) were synthesized via Flash Nanoprecipitation (FNP), a single step scalable method of nanoparticle synthesis. NPs encapsulating hydrophobic fluorophores were used to investigate rates of association, internalization, and intracellular trafficking within immortalized dorsal root ganglia (F11).

PEGylated, P2OXylated, rPEGylated, and PHEMAylated NPs demonstrated predictable and controllable size formation from 50nm to 250nm with low polydispersity, neutral to negative zeta potential, and spherical morphology. F11 cells were successfully differentiated into sensory nerve phenotypes. Flow cytometry and immunocytochemistry reveal that PEGylated NPs showed the most rapid (<30min) association and uptake with F11 cells, whereas P2OX showed the most delayed uptake.

Here, we present the first use of the F11 cell line for drug delivery investigations as a model of sensory neurons. Through the use of rPEG, P2OX, and PHEMA block copolymers, we have expanded the FNP surface material repertoire and present initial findings for in vitro performance characterizations. These findings will be used to optimize spatial and temporal drug action at sensory nerves. In particular, drug release within the endosomes of sensory neurons can be used for potent anti-nociception via G-protein coupled receptor-mediated pain pathways.