Basal cell carcinoma (BCC) is the most common cutaneous malignancy in humans. One of the most efficacious drugs used in the management of BCC is the immunomodulator, imiquimod. However, imiquimod has physiochemical properties that limit its permeation to reach deeper, nodular tumor lesions. The use of microneedles may overcome such limitations and promote intradermal drug delivery. The current work evaluates the effectiveness of using an oscillating microneedle device Dermapen either as a pre- or post-treatment with 5% w/w imiquimod cream application to deliver the drug into the dermis. The effectiveness of microneedles to enhance the permeation of imiquimod was evaluated ex vivo using a Franz cell setup. After a 24-h permeation experiment, sequential tape strips and vertical cross-sections of the porcine skin were collected and analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). In addition, respective Franz cell components were analyzed using high-performance liquid chromatography (HPLC). Analysis of porcine skin cross-sections demonstrated limited dermal permeation of 5% w/w imiquimod cream. Similarly, limited dermal permeation was also seen when 5% w/w imiquimod cream was applied to the skin that was pretreated with the Dermapen, this is known as poke-and-patch. In contrast, when the formulation was applied first to the skin prior to Dermapen application, this is known as patch-and-poke, we observed a significant increase in intradermal permeation of imiquimod. Such enhancement occurs immediately upon microneedle application, generating an intradermal depot that persists for up to 24 h. Intradermal colocalization of isostearic acid, an excipient in the cream, with imiquimod within microneedle channels was also demonstrated. However, such enhancement in intradermal delivery of imiquimod was not observed when the patch-and-poke strategy was used with a non-oscillating microneedle applicator, the Dermastamp. The current work highlights that using the patch-and-poke approach with an oscillating microneedle pen may be a viable approach to improve the current treatment in BCC patients who would prefer a less invasive intervention relative to surgery.

中文翻译：

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用于基底细胞癌的免疫调节剂的皮内递送；将机理的见解扩展到疏水性分子的固体微针增强递送中。

基底细胞癌（BCC）是人类最常见的皮肤恶性肿瘤。免疫调节剂咪喹莫特是治疗BCC的最有效药物之一。然而，咪喹莫特具有限制其渗透达到更深的结节性肿瘤病变的理化特性。微针的使用可以克服这些限制并促进皮内药物递送。当前的工作评估了使用摆动式微针设备Dermapen进行前处理或后处理，使用5％w / w咪喹莫特乳膏将药物送入真皮的效果。使用Franz细胞设置离体评估了微针增强咪喹莫特渗透的有效性。经过24小时的渗透实验，收集猪皮肤的连续胶带条和垂直横截面，并使用飞行时间二次离子质谱（ToF-SIMS）进行分析。另外，使用高效液相色谱法（HPLC）分析各个Franz细胞组分。猪皮肤横截面的分析表明5％w / w咪喹莫特乳膏的皮肤渗透受限。类似地，当将5％w / w的咪喹莫特乳膏涂在用Dermapen预处理的皮肤上时，也可见到有限的皮肤渗透性，这称为p刺。相反，当在Dermapen施用之前先将制剂施用到皮肤上时，这被称为贴戳，我们观察到咪喹莫特的皮内渗透率显着增加。这种增强会在微针应用后立即发生，生成皮内仓库，该仓库可以持续长达24小时。还证实了异硬脂酸（一种乳膏中的赋形剂）与咪喹莫特在微针通道内的皮内共定位。但是，当将贴片戳策略与非摆动式微针敷料器Dermastamp一起使用时，未观察到咪喹莫特在皮内递送方面的这种增强。当前的工作突出表明，使用摆动式微针笔修补和oke戳方法可能是一种可行的方法，可以改善BCC患者的治疗水平，而BCC患者则希望相对于手术采用侵入性较小的干预措施。当使用非摆动式微针涂抹器Dermastamp使用贴戳策略时，未观察到咪喹莫特在皮内递送方面的这种增强。当前的工作突出表明，使用摆动式微针笔修补和oke戳方法可能是一种可行的方法，可以改善BCC患者的治疗水平，而BCC患者则希望相对于手术采用侵入性较小的干预措施。当使用非摆动式微针涂抹器Dermastamp使用贴戳策略时，未观察到咪喹莫特在皮内递送方面的这种增强。当前的工作突出表明，使用摆动式微针笔修补和oke戳方法可能是一种可行的方法，可以改善BCC患者的治疗水平，而BCC患者则希望相对于手术采用侵入性较小的干预措施。