The effectiveness of topical drugs for treatment of non-melanoma skin cancer is greatly reduced by insufficient penetration to deep skin layers. Ablative fractional lasers (AFLs) are known to enhance topical drug uptake by generating narrow microchannels through the skin, but information on AFL-drug delivery in in vivo conditions is limited. In this study, we examined pharmacokinetics, biodistribution and toxicity of two synergistic chemotherapy agents, cisplatin and 5-fluorouracil (5-FU), following AFL-assisted delivery alone or in combination in in vivo porcine skin. Detected at 0–120 h using mass spectrometry techniques, we demonstrated that fractional CO₂ laser pretreatment (196 microchannels/cm², 852 μm ablation depth) leads to rapid drug uptake in 1500 μm deep skin layers, with a sixfold enhancement in peak cisplatin concentrations versus non-laser-treated controls (5 h, P = 0.005). Similarly, maximum 5-FU deposition was measured within an hour of AFL-delivery, and exceeded peak deposition in non-laser-exposed skin that had undergone topical drug exposure for 5 days. Overall, this accelerated and deeper cutaneous drug uptake resulted in significantly increased inflammatory and histopathological effects. Based on clinical scores and transepidermal water loss measurement, AFL intensified local toxic responses to drugs delivered alone and in combination, while systemic drug exposure remained undetectable. Quantitative histopathologic analyses correspondingly revealed significantly reduced epidermal proliferation and greater cellular apoptosis after AFL-drug delivery; particularly after combined cisplatin + 5-FU exposure. In sum, by overcoming the primary limitation of topical drug penetration and providing accelerated, enhanced and deeper delivery, AFL-assisted combination chemotherapy may represent a promising treatment strategy for non-melanoma skin cancer.

局部药物治疗非黑色素瘤皮肤癌的有效性因深入皮肤层的渗透不足而大大降低。已知烧蚀分数激光 (AFL) 通过在皮肤上产生狭窄的微通道来增强局部药物的吸收，但有关 AFL 药物在体内条件下递送的信息是有限的。在这项研究中，我们检查了两种协同化疗药物顺铂和 5-氟尿嘧啶 (5-FU) 的药代动力学、生物分布和毒性，在 AFL 辅助分娩后单独或联合体内猪皮肤。使用质谱技术在 0–120 小时检测到，我们证明了分数 CO ₂激光预处理（196 微通道/cm ², 852 μm 消融深度）导致药物在 1500 μm 深的皮肤层中快速摄取，与非激光治疗的对照相比，顺铂峰值浓度增加六倍（5 小时，P = 0.005）。同样，最大 5-FU 沉积是在 AFL 递送后一小时内测得的，并且超过了非激光暴露皮肤的峰值沉积，该皮肤已经经历了 5 天的局部药物暴露。总的来说，这种加速和更深的皮肤药物摄取导致炎症和组织病理学影响显着增加。根据临床评分和经表皮水分流失测量，AFL 增强了对单独和联合给药的药物的局部毒性反应，而全身药物暴露仍未检测到。定量组织病理学分析相应地揭示了 AFL 药物递送后表皮增殖显着减少和细胞凋亡增加；特别是在联合使用顺铂 + 5-FU 后。总之，通过克服局部药物渗透的主要限制并提供加速的，