Microneedle Technology for Overcoming Biological Barriers: Advancing Biomacromolecular Delivery and Therapeutic Applications in Major Diseases.

Biomacromolecules are now widely employed in the therapy of major diseases such as tumors, infections, cardiovascular diseases, metabolic diseases, and autoimmune diseases. Although significant advances have been made in their application, their administration is largely dependent on professional injection, which causes pain, massive medical waste, and high medical burden. As a novel delivery system, microneedles pierce the stratum corneum to assist in intradermal drug delivery, exhibiting minimal invasiveness, high delivery efficiency, and improved patient compliance. The evolution of biomaterials and tissue engineering has broadened microneedle utilization to encompass oral and cardiovascular therapies. Herein, we discuss research advancements regarding the development of biomacromolecule-laden microneedles for treating major diseases. We present detailed examples on how to devise functional microneedles to cross drug delivery barriers in the skin, heart, and blood vessels for improved therapeutic outcomes. Furthermore, we discuss the critical barriers in industrial-scale fabrication and transitioning into clinical practice of microneedles, aiming to provide insightful solutions. Moreover, we explore the future applications of microneedles, including the development of microneedle tacks, robots, and biomimetics to combat intractable diseases. We believe that this review will aid in the designing of microneedles for biomacromolecule delivery, opening up a new avenue for the treatment of major diseases.