(368ak) Developing Nanomaterials for Prolonged Treatment of Cancer Pain

Oral cancers are common yet difficult to treat, affecting 30,000 Americans per year. These cancers are notoriously painful, causing severe oral pain which increases as the disease progresses. Current options for treating cancer pain are limited to opioids, which have profound drawbacks, including low therapeutic duration, dependence, constipation, and nausea. Recently, calcitonin gene-related peptide (CGRP) receptors have been identified as a key target for inhibiting oral cancer pain. However, maintaining drug concentrations at the tumor microenvironment (TME) is difficult, due to rapid drug clearance from leaky tumor vasculature and enhanced lymphatic drainage.

Here, we present a nanomedicine approach to continuously inhibit the CGRP pain pathway in oral cancer. It was hypothesized that delivery of olcegepant (a CGRP antagonist) via polymeric nanocarriers would result in greater and more prolonged pain inhibition than free olcegepant due to enhanced retention of nanocarriers at the TME, and a “sustained drug release” nanocarrier design.

Olcegepant was encapsulated into PEG-PLA nanoparticles via Flash Nanoprecipitation (FNP). FNP is a well-established, one-step, controlled precipitation process for the formation of polymeric core-shell nanoparticles (NPs) with independent control over the size, drug loading and surface functionality. Hydrophobic ion pairing (HIP) with pamoic acid was employed to drive the encapsulation of the weakly hydrophobic antagonist.

This resulted in 100 nm nanoparticles with drug loadings of 4 wt.% olcegepant. Ion pairing pamoic acid with the olcegepant increased encapsulation efficiency seven-fold. Nanocarriers displayed a slow drug release profile of 80% cumulative olcegepant release over 24 hours. Nanocarriers reduced 98% mechanical and 100% thermal cancer nociception for 12 hours post-administration with a persistent reduction in pain lasting up to 24 hours in human squamous cell carcinoma (HSC-3) cancer xenograft paw and tongue mouse models—9 hours longer and 5 times greater than free olcegepant at the same dose.

By significantly improving cancer pain inhibition via nanoparticle delivery of a pain-signaling antagonist, this study presents a pioneering framework for non-addictive, long-lasting cancer pain therapies.

Research Interests:

Drug Delivery, Nanomaterials, Process development, Drug product development, Nanoscale characterization, Pharmaceuticals, Science Communication