Carboxymethylcellulose-fucoidan dissolvable microneedle patches for minimally invasive melanoma treatment: Demonstration on a 3D bioprinted A375 cell line model

Melanoma often requires adjuvant therapy to combat tumor proliferation and metastasis. In this context, microneedle systems (MNs) present a promising avenue for minimally invasive delivery of drugs or bioactive compounds with natural anticancer properties, targeting the deeper layers of the skin. Herein, we describe the fabrication of bioactive dissolving microneedles composed of carboxymethylcellulose (CMC) and fucoidan (Fuc) using a simple and eco-friendly micromolding technique. The microneedles showcased integral bodies and sharp tips with heights of 456 μm, and robust mechanical properties, reaching a maximum force of 1.07 N needle^-1. Preliminary insertion tests in a polymeric skin model demonstrated the ability of CMC_Fuc MNs to penetrate up to 381 μm, further validated in ex vivo human skin samples with insertion depths of 325-453 μm. Dissolution studies in an agarose hydrogel skin model revealed the complete dissolution of the MNs tips within 12 min. In vitro cytotoxicity assays unveiled the antitumoral effect of the CMC_Fuc MNs on A375 melanoma cells, leading to a significant cell viability reduction in both a 2D cell culture (ca. 83 %) and a 3D bioprinted melanoma culture model (ca. 56 %), after 48 h. The CMC_Fuc microneedle systems show great promise for minimally invasive adjuvant treatment of melanoma.