Microneedle-Assisted Delivery of Biologics: From Large Molecules to Cancer Vaccines.

Peptide- and protein-based biologics, including therapeutic peptides, monoclonal antibodies, and vaccines, have transformed modern therapeutics. However, they remain constrained by poor oral bioavailability, stability challenges, cold-chain dependence, and limited patient acceptability associated with injectable administration. This review critically evaluates recent technological advances, therapeutic applications, and translational progress of microneedle (MN)-assisted delivery systems for biologics, with an emphasis on insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, monoclonal antibodies, and cancer vaccines. MN platforms enable minimally invasive transdermal delivery that bypasses gastrointestinal degradation and first-pass metabolism, while facilitating intradermal immune targeting. Dissolving and polymeric MNs offer advantages such as enhanced thermostability, elimination of sharp waste, and potential reduction of cold-chain requirements, supporting broader global health deployment. Smart and responsive MNs further enable controlled and on-demand biological release in response to physiological cues. Preclinical and early phase clinical studies have demonstrated pharmacokinetic performance comparable to or exceeding conventional subcutaneous delivery for insulin, GLP-1 analogs, and selected therapeutic proteins, as well as enhanced immunogenicity for vaccines. However, clinical translation is influenced by MN type, injection volume, and device design, with some hollow MN systems associated with increased pain compared to conventional injections. Remaining challenges include scalable good manufacturing practice (GMP)-compliant production, biologic stability during fabrication and sterilization, and harmonized regulatory pathways for drug-device combination products. Overall, MN-assisted delivery represents a promising strategy for patient-centered, stable, and accessible biologic therapies.