Controlled, Tailorable Release of Therapeutics from Poly(ester urea) Matrices for Pain Management

Abstract

Acute pain remains one of the most prevalent and time-consuming clinical challenges in modern medicine. The effective management of pain post-surgically is critical to optimal patient recovery, as well as reducing hospital stays and associated medical expenses. The critical window for pain management is 3-4 days following surgery. Current clinical standards rely on frequent readministration of therapeutics and carry a high incidence of breakthrough pain as well as severe side effects depending on the class of medication and its dose. There is a critical unmet need for post-surgical pain management strategies that are safe, effective, and long-acting. One solution is the use of a drug-polymer matrix to achieve sustained release of analgesia. The class of polymers used herein are amino-acid based poly(ester urea)s (PEUs), which have previously been used for a variety of biomaterial applications, including drug delivery. PEUs are a desirable drug carrier due to their material property tunability, degradation products, and limited inflammatory response. PEUs were fabricated into thin films by blade coating or into nanofibers by electrospinning. The materials were loaded with different classes of pain management therapeutics, including local anesthetics, non-steroidal anti-inflammatory drugs, and opioids. The determining factors for release kinetics were assessed, including polymer molecular weight, formulation composition, porosity agents, material thickness, and processing method. The PEU nanofibers and thin films were used to achieve sustained drug delivery, thermal actuation, multimodal analgesia, in vivo compatibility, and effective pain inhibition for 3-4 days. Overall, this work highlights the use of PEUs as a matrix for analgesia delivery that provides effective, sustained, and superior pain management to clinical standards.