Dual therapeutic action of antibiotic-loaded nanosheets for the treatment of gastrointestinal tissue defects.
An ultra-thin polymer film (nanosheet) composed of polysaccharides (i.e., polysaccharide nanosheet) provides sufficient adhesiveness, flexibility and robustness to act as an effective wound dressing. We have recently demonstrated the sealing effect of a nanosheet on a murine cecal puncture. Nevertheless, a small percentage of bacteria penetrated the nanosheet because of its ultra-thin structure. Here, we have developed an antibiotic-loaded nanosheet to inhibit bacterial penetration and investigated its therapeutic efficacy using a model of a murine cecal puncture. Tetracycline (TC) was sandwiched between a poly(vinylacetate) (PVAc) layer and the polysaccharide nanosheet (named PVAc-TC-nanosheet). Under physiological conditions, TC was released from the nanosheet for 6 h. Microscopic observation between the interface of the PVAc-TC-nanosheet and bacteria demonstrated how its potent anti-microbial effect was achieved. In vivo studies show that overlapping therapy with the PVAc-TC-nanosheet (thickness: 177 nm) significantly increases mouse survival rate after cecal puncture as well as suppressing an increase in the intraperitoneal bacterial count and leukocyte count.
Fujie
Toshinori
T
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.
Saito
Akihiro
A
Kinoshita
Manabu
M
Miyazaki
Hiromi
H
Ohtsubo
Shinya
S
Saitoh
Daizoh
D
Takeoka
Shinji
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002432:Cecum / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D002463:Cell Membrane Permeability / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D049329:Nanostructures / Q000627:therapeutic use* / Q000648:ultrastructure; D011145:Polyvinyls / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D011145:Polyvinyls; D013752:Tetracycline