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

## TL;DR

A new three-layer dissolving microneedle patch was developed to rapidly deliver tetracycline to treat skin infections with minimal pain and systemic side effects.

## Contribution

The novel three-layer design with an effervescent separation mechanism enables rapid drug release and complete needle detachment for localized antimicrobial therapy.

## Key findings

- The patch achieved 96% penetration efficiency in ex vivo porcine skin with insertion forces of 0.848 ± 0.054 N/needle.
- The effervescent mechanism allowed complete needle detachment within 60 seconds via CO2-mediated separation.
- The system showed >99.99% reduction of E. coli and S. aureus within 6 hours at concentrations exceeding 4 × MIC.

## Abstract

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 CO2-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.