Antibiofilm Effects of Macrolide Loaded Microneedle Patches: Prospects in Healing Infected Wounds

Pharm Res. 2021 Jan;38(1):165-177. doi: 10.1007/s11095-021-02995-0. Epub 2021 Feb 3.

Abstract

Aim: The aim of this study was to fabricate polymeric microneedles, loaded with macrolides (erythromycin, azithromycin), using hyaluronic acid and polyvinyl pyrollidone.

Methods: These microneedles were fabricated using a vacuum micromolding technique. The integrity of the microneedle patches was studied by recording their morphologic features, folding endurance, swelling and micro-piercing. Physicochemical characteristics were studied by differential scanning calorimetry, thermogravimetric analysis and fourier transform infrared spectroscopy. In-vitro drug release, antibiofilm and effect of microneedle patch on wound healing were also studied to confirm the efficacy of the formulations.

Results: Formulated patches displayed acceptable folding endurance (>100) and uniform distribution of microneedles (10 × 10) that can penetrate parafilm. Differential scanning calorimetry results depict a decrease in the crystallinity of macrolides following their incorporation in to a polymer matrix. Percentage release of azithromycin and erythromycin from the polymeric patch formulations (over 30 min) was 90% and 63% respectively. Broadly, the zone of bacterial growth inhibition follows the same order for Staphylococcus aureus, Escherichia coli and Salmonella enterica. After 5 days of treatment with azithromycin patches, the wound healing was complete and skin structure (e.g. hair follicles and dermis) was regenerated.

Conclusion: It was concluded that azithromycin loaded microneedle patches can be used to treat biofilms in the infected wounds.

Keywords: azithromycin; biofilm; erythromycin; macrolide; microneedles; transdermal.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Azithromycin / administration & dosage
  • Azithromycin / pharmacokinetics
  • Biofilms / drug effects*
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Erythromycin / administration & dosage
  • Erythromycin / pharmacokinetics
  • Escherichia coli / drug effects
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Rats
  • Salmonella enterica / drug effects
  • Skin / injuries
  • Skin / metabolism
  • Skin / microbiology
  • Staphylococcus aureus / drug effects
  • Transdermal Patch
  • Wound Healing / drug effects*
  • Wound Infection / drug therapy*
  • Wound Infection / microbiology

Substances

  • Anti-Bacterial Agents
  • Erythromycin
  • Azithromycin