Detachable dissolvable microneedles maintain the viability of phage cocktail and effectively disrupt Pseudomonas aeruginosa biofilm

Abstract

The current treatment of Pseudomonas aeruginosa infection remains challenging because of antimicrobial-resistant bacteria. Phage therapy has gained more attention due to its ability to kill specific bacteria without infecting human cells. Nevertheless, phage stability in limited environments and the biofilm shield created by the pathogenic bacteria are the challenges for phage therapy implementation. To tackle the phage stability challenge, we focus on optimizing materials that can stabilize phages in a solid environment. Our research reveals that the combination of hyaluronic acid (HA) and gelatin in the solid state provides better stability for the two representative phages against P. aeruginosa, PhiKZ, and SPAO1, compared to a typical liquid medium. To solve the biofilm problem specifically in skin infection, we made the phage-loaded HA-gelatin into detachable dissolvable microneedles (DDMNs). The mechanical properties of the obtained DDMNs are sufficient to allow them to penetrate fresh ex vivo porcine skin easily. Using P. aeruginosa-inoculated membranes well shielded with biofilm created by the bacteria, our tests revealed that the phage-loaded HA-gelatin microneedles could be deposited in the bacterial-occupied membrane, disrupting the biofilm and killing P. aeruginosa.