Microneedle Patch-Mediated Treatment of Bacterial Biofilms.

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.

Acoustic disruption of tumor endothelium and on-demand drug delivery for cancer chemotherapy.

Chemotherapy has been the most widely used treatment against cancer, however, it is limited by its systemic toxicity as well as resistance developed by tumors' physical barriers. Herein, we propose a novel acoustically-mediated treatment regime to on-demand release therapeutics and disrupt tumor structures. By programming a high intensity focused ultrasound transducer, we can locally and digitally release gemcitabine (GEM) as well as open the local blood-tumor barrier or even tumor stroma to enhance intratumor drug delivery via acoustically-oscillating bubbles and liposomes. In our experiments, we modeled tumor endothelium by culturing a monolayer of murine endothelial cells (2H11) on transwell membrane. We locally disrupted the cultured endothelium to enhance drug penetration by using perfluorocarbon liquid droplets as breaking probes and protoporphyrin IX hybridized liposomes as drug carriers. We also demonstrated an on-demand release of GEM by digitally triggering the break of drug carriers. Moreover, we validated the acoustic tumor endothelium disruption in vivo by monitoring penetration of dye (Evans blue) in solid tumors. Therefore, we present an acoustically-mediated delivery method that both releases drug on-demand locally and opens the blood-tumor barrier to enhance drug penetration. This sets the ground for further clinical cancer therapy to improve many systemic cancer treatments.