Transdermal delivery of biologics using microneedle-array (MNA) based devices offers attractive theoretical advantages over prevailing oral and needle-based drug delivery methods. However, considerable practical limitations in design, fabrication, and testing are preventing the discovery of clinically relevant array designs. The goal of this project is to rationally design a cutaneous delivery platform based on a dissolvable microneedle array that enables efficient, precise, and reproducible delivery of biologically active molecules to human skin. Importantly, we propose to accomplish this with a microneedle array delivery platform that is directly applicable to patient-friendly, clinical delivery of a broad range of therapeutic agents. We have assembled a multi-disciplinary team of investigators with broad and directly relevant experience in mechanical engineering, cutaneous biology, and dermatology. Together we have developed novel and comprehensive micro-milling based fabrication technologies that uniquely position us to accomplish this goal. Through studies proposed here, we will identify geometric and mechanical properties of microneedle and array configurations that impact the effectiveness and reproducibility of MNA drug delivery. This new knowledge will be applied to the design and fabrication of MNAs with physical characteristics compatible with effective intracutaneous drug delivery. PUBLIC HEALTH RELEVANCE: Transdermal delivery of biologics using microneedle-array (MNA) based devices offers attractive theoretical advantages over prevailing oral and needle-based drug delivery methods. However, considerable practical limitations in design, fabrication, and testing are preventing the discovery of clinically relevant array designs. The goal of this project is to rationally design a cutaneous delivery platform based on a dissolvable microneedle array that enables efficient, precise, and reproducible delivery of biologically active molecules to human skin. Importantly, we propose to accomplish this with a microneedle array delivery platform that is directly applicable to patient-friendly, clinical delivery of a broad range of therapeutic agents.