Three-dimensional (3D) culture of multicellular spheroids, offering a desirable biomimetic microenvironment, is appropriate for recapitulating tissue cellular adhesive complexity and revealing a more realistic drug response.
Current treatments
of bacterial biofilms are limited by the poor
penetration of antibiotics through their physical barrier as well
as significant off-target toxicity of antibiotics and the induction
of antibiotic resistance. Here we report a microneedle patch-mediated
treatment for the effective elimination of biofilms by penetrating
the biofilm and specifically delivering antibiotics to regions of
active growth. We fabricated patches with self-dissolvable microneedles
and needle tips loaded with chloramphenicol (CAM)-bearing and gelatinase-sensitive
gelatin nanoparticles (CAM@GNPs). During the microneedle patch-mediated
treatment, arrays of 225 microneedles simultaneously penetrate the
biofilm matrix. Once inside, the microneedles dissolve and uniformly
release CAM@GNPs into the surrounding area. In response to the gelatinase
produced by the active bacterial community, the CAM@GNPs disassemble
and release CAM into these active regions of the biofilm. Moreover,
CAM@GNPs exhibited minimal off-target toxicity compared to direct
CAM administration, which in turn favors wound healing. Importantly,
we found that our microneedle-mediated treatment is more effective
in treating Vibrio vulnificus biofilms than drug
in free solution. We believe this new treatment strategy can be used
to improve the delivery of a wide range of antimicrobial agents to
biofilm-contaminated sites.
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