Advances in Monoclonal Antibody Delivery: A Materials-to-Devices Perspective on Nanocarriers, Smart Hydrogels, and Emerging Administration Platforms

Monoclonal antibodies (mAbs) underpin modern treatment of cancer, autoimmune, and chronic inflammatory disease, yet systemic administration remains pharmacologically inefficient, requiring high circulating doses that raise off-target toxicity and waste costly biologics. This review organizes the material- and device-based delivery systems developed over the past five years along a materials-to-devices axis spanning inorganic and organic nanocarriers, stimuli-responsive hydrogels, microneedles, and integrated device platforms. Across these platforms, controlled release is achieved primarily through size exclusion via engineered pore structures or by tuning the degradation rate of the encapsulating matrix, while stimuli-responsive chemistries add temporal-spatial control through phase, conformational, or degradation changes triggered by internal or external cues. The review assesses progress across a consistent set of criteria spanning payload performance, biocompatibility, tissue penetration, manufacturability, and regulatory readiness. We find that material systems lead in loading capacity and release control while device platforms lead in tissue penetration and programmable, feedback-controlled dosing, with localized delivery consistently lowering peak systemic exposure relative to free-antibody administration. However, progress is uneven: carrier biocompatibility and long-term in vivo safety remain incompletely characterized across platform classes, and antibody bioactivity can be compromised by the same stimuli used to trigger release. Manufacturability and regulatory readiness are the least developed dimensions across every platform class, forming the primary bottleneck to clinical translation, particularly for combination products that single-function regulatory frameworks do not accommodate. Advancing the field will require head-to-head trials against standard-of-care injections, long-term safety and adherence data, scalable cGMP manufacturing, dedicated regulatory pathways, and standardized assays for antibody bioactivity under device-activation conditions.