Advancing transdermal drug delivery: integration of microneedle technology and iontophoresis for enhanced therapeutic outcomes.

INTRODUCTION: Integrated microneedle - iontophoresis (MN - ITP) systems are emerging as a promising approach to improve transdermal drug delivery. These work by dual effect such as mechanical disruption of the stratum corneum along with electrically driven transport. This approach has gained increasing attention for both small molecules and macromolecules, offering the possibility of controlled, minimally invasive administration with improved pharmacokinetic outcomes compared with conventional methods. AREAS COVERED: This review highlights MN - ITP strategies for transdermal delivery, based on a targeted search of major databases, patents, and FDA guidance (1984-2026), emphasizing therapeutic applications since 2015. Different MN-ITP device designs investigated for small molecules as well as larger therapeutics such as peptides, proteins, and vaccines have been discussed. The review focuses on how device design, drug properties, and delivery performance influence outcomes, and compares integrated simultaneous systems with sequential MN - ITP approaches. EXPERT OPINION/COMMENTARY: Current evidence indicates that integrated MN - ITP systems can enhance transdermal delivery, though outcomes depend on drug properties, loading strategies, and electrical parameters. Combined systems often act complementarily rather than uniformly superior, highlighting the need for rational, drug-specific design. Future work should focus on wearable and closed-loop platforms, optimized current density and MN architecture, and clinical translation.