Additive Accelerated Meloxicam Release from Poly(Ester Urea) Fiber Implants for Acute Pain Management.

Abstract

Current clinical pain management strategies rely heavily on orally prescribed opioids, especially oxycodone, as opposed to non-steroidal anti-inflammatory drugs (NSAIDs) or local anesthetics. Implanted devices that facilitate controlled, localized delivery of NSAIDs could sustain higher drug concentrations at the surgical site and extend pain management efficacy beyond oral or intravenous methods. Meloxicam-loaded poly(ester urea) (PEU) nanofibers are fabricated with variations in polymer molecular mass, additives, additive loads, and substrate thickness to assess their respective influence on sustained meloxicam release. Nanofiber mats loaded with meloxicam and sodium bicarbonate demonstrated superior pain inhibition for three days over intraperitoneal (IP) and intramuscular (IM) injections of meloxicam in a murine tibial fracture pain model. Biopsies of muscle tissue surrounding the fracture, one day post-treatment, possessed high meloxicam concentrations relative to plasma and significantly reduced Ptgs2 expression and COX-2 inhibition. This work demonstrates the extended performance of local meloxicam-loaded PEU implants with significant pain and inflammation suppression.