Dissolvable Self‐Locking Microneedle Patches Integrated with Immunomodulators for Cancer Immunotherapy

Abstract Advancements in micro‐resolution 3D printers have significantly facilitated the development of highly complex mass‐producible drug delivery platforms. Conventionally, due to the limitations of micro‐milling machineries, dissolvable microneedles (MNs) are mainly fabricated in cone‐shaped geometry with limited drug delivery accuracy. Herein, to overcome the limitations of conventional MNs, a novel projection micro‐stereolithography 3D printer‐based self‐locking MN for precise skin insertion, adhesion, and transcutaneous microdose drug delivery is presented. The geometry of self‐locking MN consists of a sharp skin‐penetrating tip, a wide skin interlocking body, and a narrow base with mechanical supports fabricated over a flexible hydrocolloid patch to improve the accuracy of skin penetration into irregular surfaces. Melanoma, a type of skin cancer, is selected as the model for the investigation of self‐locking MNs due to its irregular and uneven surface. In vivo immunotherapy efficacy is evaluated by integrating SD‐208, a novel transforming growth factor‐β (TGF‐β) inhibitor that suppresses the proliferation and metastasis of tumors, and anti‐PD‐L1 (aPD‐L1 Ab), an immune checkpoint inhibitor that induces T cell‐mediated tumor cell death, into self‐locking MNs and comparing them with intratumoral injection. Evaluation of (aPD‐L1 Ab)/SD‐208 delivery effectiveness in B16F10 melanoma‐bearing mice model confirms significantly improved dose efficacy of self‐locking MNs compared with intratumoral injection.