After surgery, effective pain management is one of the most critical aspects of patient recovery. Treatment requirements can vary from person to person, leading to high variability in management strategies. As a result, physicians may prescribe analgesic (pain-relieving) drugs in excess, allowing patients to take them “as needed.” While this method is effective, it also increases the rate of unauthorized distribution, furthering risk of opioid addiction. In addition, drugs administered systemically—orally or intravenously, as opposed to locally—pose a higher risk for adverse effects, such as fatigue and cardiovascular dysfunction.
To combat these issues, a team of scientists at Duke University led by professor Matthew Becker, alongside graduate student Natasha Brigham, created a potential solution: bio-resorbable poly(ester urea) films (PEUs). These synthetic polymer films contain etoricoxib, an inhibitor for COX-2, an enzyme involved in inflammation. They are designed to deliver pain-management at the site of operation. After the drug has been released, the biomaterial breaks down into components safely tolerated by the body.
Becker and his team are not the first to create a film for surgical-site pain relief. Synthetic polymers are physically and chemically tunable, and resorbable ones are particularly appealing as they are considered temporary devices. In fact, poly(lactic-co-glycolic acid) films (PLGAs) have previously been used for analgesic delivery. However, this material presents some problems that result in non-linear release of the active pharmaceutical ingredient (API). For one, the PLGAs can be semi-crystalline, a structure that excludes the API. Additionally, the biomaterial degrades through various mechanisms that result in acidic byproducts, causing tissue inflammation and damage to the API.
In contrast, the etoricoxib PEU films created by Becker’s team circumvent all of these problems. The structure is amorphous (non-crystalline) due to powerful hydrogen bonding and flexible diol connections. “In the PEUs… the drug interacts strongly with the polymer, and allows for more uniform distribution of the drug,” Becker said. As the release profile of the API is nearly constant, the elution is likely only dictated by one mechanism and does not involve polymer degradation.
Besides the benefits of their general structure, these films can be customized from the polymer itself to different thicknesses and drug saturations. The scientists first tested two drug-loads, twenty percent and forty percent, in two types of amino acid-based polymers. They found that the higher-loaded film releases more API per time point; thus, films with greater drug loads could be used as longer-acting implants. Additionally, they discovered that different polymer compositions, while maintaining a continuous release profile, exhibit various release percentages due to how etoricoxib interacts with the polymer. Finally, film thickness affects diffusion, in that thicker films release the API at the same rate but for a longer duration.
The theoretical efficacy of these films was proven in rat models, in which a PEU wrapped around the sciatic nerve restored normal pain threshold for up to five days. All of these factors promise a more predictable and controllable drug diffusion, which would provide patients with prolonged pain relief. “This is another tool in the toolbox for physicians to offer their patients,” Becker said. “It wouldn’t feel different [than an oral drug], you can control it locally… and it doesn’t face the challenges of illegal distribution since it’s sewn in.” With time and refinement, local drug delivery systems have the potential to transform the standard of care for post-operative pain management.