Microliter-scale ethanol confinement array with biofluidic triggered release for dual-enhanced precision chemotherapy

Ethanol is a low-cost, water-insoluble solubilizer for chemotherapeutics and a tumor ablator in various clinical settings. Three-dimensional (3D) precise control over the flow path of liquid formulations during treatment is crucial for accurate lesion dosing, minimizing damage to adjacent tissues, and reducing systemic inflammation. Herein, we created a microliter cavity structure within an ethanol-resistant, water-dissolvable microneedle array sealed with an adhesive, denoted as APE-PCMN. This design effectively prevents volatilization of ethanol (up to 7 days) and microbial invasion at the insertion sites. Using paclitaxel (PTX) as a typical water-insoluble drug, we demonstrated the dual effects of solubilization and locoregional ablation by ethanol in the inhibition of melanoma with two administrations. Microliter-scale scattered delivery reduced skin necrosis and systemic inflammation compared to intratumoral injection in vivo. The biofluidic-responsive, 3D coverable ethanol capsule microarray approach offers a detachable, home-friendly, and minimally invasive strategy for precision chemotherapy.