Development of a novel sustained release local anesthetic wound dressing for partial-thickness dermal injuries

项目摘要 与浅表和部分皮肤层伤口相关的疼痛可能是强烈和持续的 在整个愈合过程中。疼痛管理不当会损害伤口愈合，延长 住院、降低患者满意度和增加医疗保健成本。由于有限的治疗选择和 目前的局部麻醉制剂持续时间短，阿片类镇痛药是疼痛的主要药物 尽管这些患者与各种不良事件相关，但仍需要对这些患者进行管理。因此，疼痛 由于提供者缺乏安全有效的阿片类药物替代品， 他们的病人 109 Therapeutics正在开发BUPIVADERM，这是一种新型的药物输送伤口敷料，可提供持续的 布比卡因以预测和延长的方式递送至部分厚度的皮肤伤口。新伤口 敷料将是第一种伤口敷料， 湿性伤口敷料临床可用，但增加了安全有效的镇痛功能， 天该敷料仅需使用一次，一旦上皮再形成，即可无创剥离 因此无需更换敷料或重新给药止痛剂。该新型伤口敷料将 通过提高患者满意度，减轻患者的痛苦，为患者，临床医生和社会提供重要价值。 阿片类药物的使用，以及降低部分皮层皮肤伤口治疗的护理成本。 在初步的实验中，我们已经证明了制造布比卡因负载的微孔 聚合物薄膜具有与当前金标准湿膜相同的尺寸和物理化学性质 伤口敷料，但具有提供5天持续布比卡因递送的额外能力。拟议 工作将寻求通过验证安全性来证明新型伤口敷料的体内技术可行性， 我们的原型在标准化猪皮肤损伤模型中的伤口愈合和镇痛功效。镇痛 将通过机械敏感性的von Frey测定来评估疗效和持续时间， 通过大体和组织学试验评估，全身毒性将通过药代动力学评估 考核拟议的第一阶段工作将证明我们的新的持续布比卡因释放伤口 敷料可提供5天安全有效的非阿片类镇痛和非劣效性伤口愈合， 临床相关的临床前模型，这将保证继续商业化的努力。

PROJECT SUMMARY The pain associated with superficial and partial-thickness dermal wounds can be intense and sustained throughout the healing process. Inadequate pain management can impair wound healing, prolong hospitalization, decrease patient satisfaction and increase healthcare costs. Due to limited treatment options and the short duration of current local anesthetic formulations, opioid analgesics are the mainstay of pain management for these patients despite their association with a variety of adverse events. Consequently, pain from dermal injury is not optimally treated because providers lack a safe and effective alternative to opioids for their patients. 109 Therapeutics is developing BUPIVADERM, a novel, drug-delivering wound dressing that provides sustained bupivacaine delivery to partial-thickness dermal wounds in a predictive and extended manner. The novel wound dressing will be a first-of-kind wound dressing that provides both the wound healing properties of the traditional moist wound dressings clinically available, but with the added functionality of safe and effective analgesia for 5 days. The dressing will only need to be applied one time and non-traumatically peels off once re-epithelialization occurs, thus eliminating the need for dressing changes or analgesic redosing. The novel wound dressing will provide significant value to patients, clinicians, and society alike by increasing patient satisfaction, mitigating the use of opioids, and reducing cost of care in the treatment of partial-thickness dermal wounds. In preliminary experiments, we have demonstrated the ability to fabricate bupivacaine-loaded microporous polymer films that have the same dimensions and physicochemical properties of the current gold standard moist wound dressings, but with the added ability to provide 5 days of sustained bupivacaine delivery. The proposed work will seek to demonstrate in vivo technical feasibility of the novel wound dressing by validating the safety, wound healing and analgesic efficacy of our prototype in a standardized porcine dermal injury model. Analgesic efficacy and duration will be assessed by von Frey assay of mechanical sensitivity, wound healing will be assessed via gross and histological assays, and systemic toxicity will be assessed via pharmacokinetic assessment. The proposed Phase I work will demonstrate that our novel sustained bupivacaine release wound dressing can provide 5 days of safe and effective non-opioid analgesia and non-inferior wound healing in a clinically relevant pre-clinical model, which would warrant continuation of commercialization efforts.