Multiresponsive Nanogels for the Selective Delivery of Antimicrobial Drugs to Mucosal Tissues

Effective drug delivery to bacterially infected mucosa remains a challenge due to the combined obstacles of the mucosal barrier, pH variations, and high concentrations of glutathione. However, polysaccharide-based responsive nanogels (NGs) can take advantage of these conditions to deliver specific antimicrobials. We explored the critical features of pH- and redox-responsive NGs to increase drug penetration, residence time, and efficacy in the infected mucosa. We prepared multifunctional NGs using hydroxypropyl cellulose as a template for the cross-linking of methacrylic acid with N,N'-bis(acryloyl)cystamine (BAC) or N,N'-methylenebis(acrylamide) (BIS). Studies of NG-mucin binding and the antibacterial efficacy of doxycycline-loaded NGs revealed the interplay between the response to pH and redox clues. Specifically, higher BAC composition increased mucus binding and controlled release in reductive conditions, while higher BIS composition yielded NGs with higher doxycycline-mediated antibacterial efficacy against Staphylococcus aureus. The findings reveal the potential of multiresponsive NGs in effective antimicrobial delivery in infected mucosa.