Transdermal microneedles integrating biomimetic self-adjuvant particles for enhanced immunity

Optimal exposure and interaction of subunit antigens with the immune system are crucial for effective immunity. The epidermis and dermis, which harbor a significant population of antigen-presenting cells (APCs) and are broadly connected to the lymphatic system, serve as ideal sites for immunization to fulfill these objectives. However, the stratum corneum barrier severely hinders transdermal delivery of antigens. Here, we developed a transdermal platform integrating yeast-derived biomimetic glucan particles (GPs) and polymeric microneedles to overcome the hurdles and induce effective immunity. GPs served as carriers for encapsulating antigens in a pathogen-like manner. The antigen-loaded particles were concentrated within the tips of polymeric microneedle to solidify as tiny reservoirs, while the needle bodies were shaped using a fast-dissolving matrix. This tip-loaded approach enabled rapid administration for better compliance, followed by an extended antigen release at administration sites, aiming for recruiting more APCs. This microscale platform capacitated a multi-functional approach for subunit vaccine development by optimizing both delivery carriers and dosage forms with modulated release mechanisms to enhance antigen exposure and interaction, thereby promoting effective humoral and cellular immunity.