Advanced in Co-Delivery, Controllable Therapy using Microneedle: From Design to Therapeutic Effects

Microneedles (MNs) provide a minimally invasive and efficient platform for transdermal drug delivery, offering precise control over dosage and release kinetics. Recent advances in dual-drug delivery using dissolvable MNs have focused on optimizing structural design, material composition, and programmable release mechanisms. Dual-layer or core-shell MN configurations allow spatial and temporal separation of drugs, while stimuli-responsive polymers enable release in response to physiological cues such as glucose concentration, pH, or reactive oxygen species (ROS). This review summarizes emerging strategies for co-delivery through dissolving MNs, emphasizing how design parameters including morphology, materials, and nanoformulations influence mechanical performance and drug-release profiles. Applications in cancer, diabetes, wound healing, and inflammatory diseases are highlighted. For example, a dual-drug MN co-loaded with an anti-PD-L1 antibody and 1-methyl-D,L-tryptophan (1-MT) achieved prolonged intratumoral retention and enhanced antitumor efficacy. Similarly, MNs incorporating MnSH nanozymes and polymyxin B demonstrated synergistic antibacterial and pro-angiogenic effects in wound models. The integration of nanocarriers and responsive polymers has expanded the therapeutic potential of MN-based systems, enabling precise, localized, and sustained co-delivery of active agents. Finally, current challenges including large-scale manufacturing, reproducibility, clinical validation, and regulatory approval are discussed to outline future directions for translating MN-based dual-drug delivery into clinical practice.