The opioid crisis continues to loom large, only exacerbated by the current COVID-19 pandemic (1). Medical prescriptions for the alleviation of postoperative pain remain the primary source of opioids in circulation, and, to this day, opioids continue to ravage patient populations due to unauthorized use and distribution and over-prescription in some cases, alongside associated addiction and death. Side effects of opioid analgesia can include nausea, vomiting, sedation, respiratory depression and addiction (2), and severe postoperative pain is still reported by 20-40% of patients, especially in those having undergone abdominal, thoracic, orthopedic and pelvic surgeries (3). Furthermore, the current standard of care is the prescription of orally dosed opioid medication, which requires the patient to determine the frequency of dosing, and results in systemic biodistribution that loses efficiency by impacting healthy tissues, which is detrimental to patient health and may incur significant lasting effects. It is thus increasingly important to develop effective, safe, and viable alternatives to orally administered opioid-based postoperative pain medications (4). To this end, analgesic patches and films have proven increasingly promising.
Clinically, analgesic patches for postoperative pain management have taken on a variety of forms. First, lidocaine patches have long been used for postoperative pain treatment in a variety of contexts (5). For example, adjuvant treatment after total knee arthroplasty using lidocaine patches was found to be effective in reducing pain and decreasing the use of opioids, representing a viable component of multimodal analgesic therapy (6). Second, transdermal patches of buprenorphine, an opioid partial agonist, is also widely used for chronic pain syndromes, and, increasingly, acute postoperative pain (7,8). Finally, transdermal fentanyl patches have also been well-established for the effective management of acute postoperative pain (9). Remarkably, one study showed that a patch affixed 14 hours prior to surgery reached a higher constant concentration than the same dose setting of a constant intravenous infusion of fentanyl after surgery (10), without incurring any respiratory depression or other nefarious side effects.
In addition, both natural and synthetic polymers (including poly(anhydrides), poly(orthoesters), poly(esters), and poly(esteramides)) have garnered recent attention for their potential to deliver analgesia via implantable films, making drugs directly available to local tissue without any physical barriers (4,11). Most recently, a bio-resorbable poly(ester urea) film that delivers the non-opioid COX-2 inhibitor etoricoxib has emerged as a particularly promising model system for postoperative pain control (12). Poly (ester urea) composition, drug load, and film thickness can be finetuned to control etoricoxib elution, and pharmacokinetic data from an in vivo rat model showed the local tissue concentration of etoricoxib to be up to 23-fold higher in tissue then plasma. Importantly, applications extend beyond post-surgical pain; in a well-established mouse model of diabetic neuropathic pain, in vivo film implantation yielded efficient local etoricoxib delivery and effective pain relief for over 4 days post-implantation (12).
Multimodal postoperative pain management, including in the form of analgesic patches and films, require lower daily doses to achieve pain relief and aim to act specifically at the affected site, incurring less pronounced metabolic changes, minimal systemic side effects, and fewer drug interactions (13). Clinically, such alternative forms of non-opioid-based pain management systems are critical to curbing the opioid crisis while optimizing the patient experience, thereby warranting ongoing research and development efforts geared towards their efficient clinical implementation.
References
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