Development and characterization of a novel reverse microemulsion analgesic delivery system capable of reducing post-burn mechanical allodynia and thermal hyperalgesia

Pain control following thermal injury remains a significant clinical challenge from the initial point of care through rehabilitation. Although standard analgesics provide some relief, there is a critical need to better modulate burn pain while minimizing the undesirable side effects associated with current systemic pain treatments. To that end, we developed a novel reverse microemulsion (RmE) that encapsulated the polar and ionic analgesics nordihydroguaiaretic acid (NDGA) and ketoconazole with 10–20% efficiency and could deliver the analgesics into bioartificial tissues. When RmE-analgesic formulations were incorporated into a liquid bandage-like amphiphilic acrylate polymer, the analgesics were released slowly over 24 hours. Incorporation into the amphiphilic acrylate polymer slowed analgesic release from the RmE and the majority of the analgesics remained in the topically-applied residual polymer layer. Both the RmE and the polymer-RmE formulations induced significant reductions in post-burn pain for at least 48 h. Altogether, these data suggest a RmE loaded with NDGA and ketoconazole can act as a novel long-acting and topical method for reducing thermal hyperalgesia and mechanical allodynia nociceptive responses.