Polymersome‐mediated intracellular delivery of antibiotics to treat Porphyromonas gingivalis‐infected oral epithelial cells

The gram‐negative anaerobe Porphyromonas gingivalis colonizes the gingival crevice and is etiologically associated with periodontal disease that can lead to alveolar bone damage and resorption, promoting tooth loss. Although susceptible to antibiotics, P. gingivalis can evade antibiotic killing by r...

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Bibliographic Details
Published in:The FASEB journal 2013-11, Vol.27 (11), p.4455-4465
Main Authors: Wayakanon, Kornchanok, Thornhill, Martin H., Douglas, C. W. Ian, Lewis, Andrew L., Warren, Nicholas J., Pinnock, Abigail, Armes, Steven P., Battaglia, Giuseppe, Murdoch, Craig
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - therapeutic use
antimicrobial chemotherapy
Bacteroidaceae Infections - drug therapy
Cells, Cultured
Doxycycline - administration & dosage
Doxycycline - therapeutic use
Gingiva - microbiology
Gingiva - pathology
Gingival Diseases - drug therapy
Humans
Keratinocytes - microbiology
Metronidazole - administration & dosage
Metronidazole - therapeutic use
Nanocapsules - chemistry
nanotechnology
periodontal disease
Periodontitis - drug therapy
Polymers - chemistry
Porphyromonas gingivalis
Porphyromonas gingivalis - drug effects
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Summary:The gram‐negative anaerobe Porphyromonas gingivalis colonizes the gingival crevice and is etiologically associated with periodontal disease that can lead to alveolar bone damage and resorption, promoting tooth loss. Although susceptible to antibiotics, P. gingivalis can evade antibiotic killing by residing within gingival keratinocytes. This provides a reservoir of organisms that may recolonize the gingival crevice once antibiotic therapy is complete. Polymersomes are nanosized amphiphilic block copolymer vesicles that can encapsulate drugs. Cells internalize polymersomes by endocytosis into early endosomes, where they are disassembled by the low pH, causing intracellular release of their drug load. In this study, polymersomes were used as vehicles to deliver antibiotics in an attempt to kill intracellular P. gingivalis within monolayers of keratinocytes and organotypic oral mucosal models. Polymersome‐encapsulated metronidazole or doxycycline, free metronidazole, or doxycycline, or polymersomes alone as controls, were used, and the number of surviving intracellular P. gingivalis was quantified after host cell lysis. Polymersome‐encapsulated metronidazole or doxycycline significantly (P
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.12-225219