Fabrication of gentamicin sulphate laden stimulus responsive polymeric microarray patches for the treatment of bacterial biofilms

Treatment of microbial biofilms by conventional topical dosage forms remains a challenge due to the presence of extracellular polymeric substances, necrotic tissues and cellular debris. An advanced drug delivery system such as a microarray patch can breach these barriers and deliver antimicrobial agents to deep-seated pathogens. This study aimed to fabricate gentamicin sulphate laden dissolving microarray patches, comprising of sodium hyaluronate, gelatin, polyvinyl alcohol and D-sorbitol, by using vacuum micromoulding approach. Morphological and phase analysis of patches were carried out by scanning electron microscopy, and differential scanning calorimetry (DSC), X-ray diffraction (XRD), respectively. In silico analysis was performed to study the molecular interactions between substrates (sodium hyaluronate and gelatin) and enzymes (hyaluronate lyase and gelatinase). In vitro insertion ability, stimulus-responsiveness, drug release study, antimicrobial assay, antibiofilm activity and in vivo antibiofilm activity were performed to assess the efficiency of prepared formulation. The patches displayed sharp-tipped, uniform-surfaced and equidistant microprojections. DSC and XRD results revealed that the microarray patch is an amorphous solid. In silico analysis indicated non-covalent interactions between substrates and enzymes. In vitro insertion test confirmed piercing ability of microarrays. Stimulus i.e., enzymes hyaluronate lyase and gelatinase responsiveness of sodium hyaluronate and gelatin, respectively was confirmed by liquefaction of media. During in vitro release study, 96 +/- 2.6% antibiotic was released within 150 min. The patches exhibited antibacterial effect against Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Salmonella enterica (S. enterica). The biomass of S. aureus and P. aeruginosa biofilms was significantly reduced (>= 70%), in vitro, following treatment with antibiotic laden patches. S. aureus infected wounds were completely healed after 11 days of treatment with prepared patches. In conclusion, fabricated microarray patches can be used for an on-site stimulus responsive administration of gentamicin sulphate and management of S. aureus infected cutaneous wounds.