Effervescent-Assisted Dissolving Microneedle Array Patches for Localized Tetracycline Delivery: A Three-Layer Design for Rapid-Onset Antimicrobial Therapy in Superficial Skin Infections

High Resolution Image Download MS PowerPoint Slide Dissolving microneedle array patches (DMNAPs) offer promise for minimally invasive antimicrobial therapy but face challenges in achieving rapid drug release and complete needle deposition. This study developed and characterized a novel three-layer DMNAP incorporating an effervescent separation mechanism for enhanced tetracycline hydrochloride (TCH) delivery to infected superficial tissues. DMNAPs were fabricated using sequential casting with drug-loaded poly(vinyl alcohol) (PVA) microneedles, an effervescent separation layer (sodium bicarbonate/tartaric acid), and a polyvinylpyrrolidone (PVP) backing. Mechanical properties, skin penetration efficiency, drug release kinetics, antimicrobial efficacy against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923, and biocompatibility using human dermal fibroblasts were systematically evaluated. The optimized PVA-1.0/PVP0.75 formulation achieved insertion forces of 0.848 ± 0.054 N/needle with penetration depths of 426.1 ± 16.8 μm and 96% penetration efficiency in ex vivo porcine skin. The effervescent mechanism enabled complete needle detachment within 60 s through CO 2 -mediated separation. TCH release followed Korsmeyer–Peppas kinetics ( R 2 > 0.93, n = 0.43–0.45), achieving >90% cumulative release within 24 h through quasi-Fickian diffusion. The system demonstrated potent bactericidal activity with >99.99% reduction of both bacterial strains within 6 h at concentrations exceeding 4 × MIC. Qualitative preliminary ex vivo antimicrobial assessment on infected porcine skin confirmed complete suppression of E. coli and substantial inhibition of S. aureus growth. Human dermal fibroblast viability remained >82% for therapeutic formulations (0.5–1.0 mg/mL TCH), confirming biocompatibility. This effervescent-assisted DMNAP platform addresses critical limitations of current microneedle technologies, offering painless, self-administrable antimicrobial therapy with minimized systemic exposure for treating antibiotic-resistant superficial infections.