Multifunctional Microneedle Patches With Sequential Drug Release For Synergistic Treatment Of Infectious Keratitis

To develop a multifunctional core-shell microneedle system capable of sequential and spatiotemporal delivery of antimicrobial peptides (AMPs) and mesenchymal stem cell-derived exosomes (MSC-exos) for synergistic antimicrobial and regenerative therapy in infectious keratitis.

In vitro cellular and antibacterial experimental systems and an in vivo rat model of infectious keratitis were used to evaluate antibacterial efficacy, anti-inflammatory effects, and corneal tissue regeneration.

A core-shell structured microneedle system was fabricated.The shell, composed of pH-responsive oxidized hyaluronic acid (OHA)/carboxymethyl chitosan (CMCS), encapsulated AMPs for infection-site-triggered release to reduce microbial load and disrupt biofilms.The core, composed of hyaluronic acid methacrylate (HAMA), encapsulated MSC-exos for sustained delivery of bioactive molecules to promote tissue repair. Antibacterial activity, anti-biofilm effects, cell migration, and anti-inflammatory properties were evaluated in vitro. Therapeutic efficacy was further assessed in a rat model of infectious keratitis.

The microneedle system exhibited superior antibacterial and anti-biofilm efficacy in vitro, significantly enhanced cell migration, and exerted potent anti-inflammatory effects. In vivo, treatment markedly reduced corneal opacity, accelerated re-epithelialization, and alleviated inflammatory responses in rats with infectious keratitis.

The developed core-shell microneedle system enables sequential antimicrobial and regenerative therapy by integrating rapid infection control with sustained tissue repair. This strategy provides a promising synergistic therapeutic approach for infectious keratitis treatment.