(153a) Slow-Release Nanoparticles for Chronic Pain Management | AIChE

(153a) Slow-Release Nanoparticles for Chronic Pain Management


Lewis, P. - Presenter, Princeton University
Pollard, R., NYU Tandon School of Engineering
Latorre, R., NYU College of Dentistry
Jensen, D., NYU College of Dentistry
Schmidt, B., NYU College of Dentistry
Bunnett, N., NYU College of Dentistry
Pinkerton, N. M., New York University
A reliable, non-habit-forming treatment for chronic pain has been elusive due to the rapid bodily clearance and short therapeutic effects of traditional opioids. To reduce opioid dependence, there is a need for a therapy which achieves robust pain inhibition for extended periods of time. Recent studies have shown that delivering drugs directly to spinal neuron endosomes yields more potent inhibition of key pain-signaling pathways. Additionally, nanomedicine has shown promise in promoting endosomal uptake for anticancer therapeutics. To translate this strategy to pain therapy, it must be demonstrated that antinociceptive drugs can be efficiently encapsulated into nanoparticles, while controlling their release rate to prolong drug activity. Here, we develop a polymeric nanoparticle drug delivery platform for the sustained release of pain-signaling antagonists in spinal neuron endosomes.

Hydrophobic ion pairing (HIP), a method of solubility tuning, has been shown to promote the encapsulation of small molecule drugs within polymeric nanoparticles. We hypothesized that employing hydrophobic counterions during nanoparticle assembly would both increase the encapsulation efficiency of a calcitonin gene-like receptor (CLR) antagonist and slow the diffusion rate of this antinociceptive drug from the nanoparticle core.

The CLR antagonist and hydrophobic counterions were encapsulated by amphiphilic block copolymers via Flash Nanoprecipitation (FNP), a rapid and size-tunable nanoparticle assembly process. Synthesis parameters including counterion species, drug/counterion molar ratios, and solvent systems were varied to optimize nanoparticle drug loading (wt.%) and in vitro drug release rates.

Pairing of the CLR antagonist with pamoic acid resulted in nanoparticles (100 nm in diameter) with drug loadings of up to 6 wt.% and encapsulation efficiencies of up to 80%, with stability observed for over two weeks. These formulations demonstrated sustained drug release in sink condition release media for over nine days.

The reproducible encapsulation of an antinociceptive drug demonstrates the ability for endosomal uptake by spinal neurons, preventing rapid clearance. In achieving high drug loading compositions and sustained drug release on the order of weeks, such formulations are optimal for the potent and prolonged inhibition of the CLR pain-signaling pathway, presenting a reproducible framework for chronic pain therapies.