Novel Barbed Microneedle Array-Mediated Dual-Drug Delivery for Thick Infantile Hemangiomas

Infantile hemangiomas (IHs) can lead to significant complications during the proliferative phase, particularly in thick lesions that are not adequately controlled by topical timolol due to its limited skin penetration. Oral propranolol is effective but limited by systemic side effects and resistance. To overcome these challenges, we developed a novel barbed microneedle (MN) system for depth-specific dual-drug delivery. Bleomycin (BLM) is loaded in the needle tips for deep ablation, while timolol (TM) is incorporated in the base hydrogel for superficial vasoconstriction, enabling synergistic therapy (TM-BLM@MN). The barbed structure secured prolonged retention in vivo. In vitro, the TM-BLM@MN significantly inhibited hemangioma stem cell proliferation, migration, and tube formation. In vivo, treatment of TM-BLM@MN achieved a 1.93-fold greater reduction in tumor volume compared to controls and markedly suppressed pathological angiogenesis by histology. TM-BLM@MN as a minimally invasive platform demonstrates high efficacy for thick IH and holds strong potential for clinical translation and home-based therapy.