Advances in Microneedle Drug Delivery for Obesity: Mechanisms, Applications, and Perspectives.

Obesity is a multifactorial metabolic disorder associated with increased risks of diabetes, cardiovascular disease, and other comorbidities. Conventional pharmacological interventions are often limited by poor patient adherence, systemic side effects, and suboptimal drug bioavailability. Microneedle (MN)-based transdermal drug delivery systems have emerged as a promising alternative, offering minimally invasive, painless, and patient-friendly administration. MN platforms not only bypass gastrointestinal degradation and hepatic first-pass metabolism but also enable targeted delivery to adipose tissue, thereby reducing systemic toxicity. Recent studies have demonstrated the potential of MNs to deliver diverse therapeutic agents, including small molecules, peptides, nucleic acids, and nanoparticles, for regulating adipose tissue metabolism, modulating the inflammatory microenvironment, and promoting browning of white adipose tissue. Various MN designs, such as dissolving, hydrogel-forming, and stimuli-responsive systems, allow precise control over release kinetics, ranging from ultrarapid drug exposure to long-term sustained delivery. Despite these advantages, several key challenges hinder clinical translation, including limited drug loading capacity, interindividual variability in skin penetration, potential local skin reactions with chronic use, and the difficulty of scaling up MN fabrication to Good Manufacturing Practice (GMP) standards while maintaining reproducibility and quality. Future perspectives emphasize the integration of nanocarrier systems, artificial intelligence-driven MN design, and multifunctional wearable devices to achieve personalized and adaptive therapy. With continued technological and translational advances, MN-based delivery could enable a new approach for obesity treatment, pending robust clinical validation.