<p>Labetalol is an anti-hypertensive medication available in both tablet and liquid injectable forms. However, a transdermal delivery system may offer a more convenient option for patients requiring this medication. Due to its solubility in organic solvents and high molecular weight, a transdermal patch could face challenges in effectively delivering the drug through the stratum corneum, the outermost layer of the skin. To overcome this challenge, labetalol-loaded nanoparticles were prepared using a solvent evaporation method and incorporated into dissolvable microneedle patches. The nanoparticles ensured controlled drug release, while microneedles facilitated drug penetration through the stratum corneum. The patches were formulated with hydroxypropyl methylcellulose and carbopol polymers and evaluated for their mechanical properties, penetration efficacy, drug loading, in vitro drug release, and biological safety. Scanning electron microscopy confirmed uniform nanoparticle distribution, and drug loading efficiency reached 95.25 ± 1.68%. The optimized formulation achieved a sustained in vitro drug release of 89.27 ± 2.34% over 24&#xa0;h, significantly improving release efficiency compared to conventional oral and injectable labetalol formulations. In contrast to the burst release observed with oral and injectable formulations, the microneedle patch offered controlled and sustained release, enhancing therapeutic outcomes and reducing side effects. Penetration studies demonstrated successful nanoparticle delivery into deeper skin layers, while irritation studies confirmed the safety of the patches. These findings suggest that nanoparticle-loaded dissolvable microneedle patches provide a promising strategy for the transdermal delivery of labetalol, offering controlled drug release and enhanced patient compliance.</p>