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 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<0.05) reduced the number of intracellular P. gingivalis in both monolayer and organotypic cultures compared to free antibiotic or polymersome alone controls. Polymersomes are effective delivery vehicles for antibiotics that do not normally gain entry to host cells. This approach could be used to treat recurrent periodontitis or other diseases caused by intracellular-dwelling organisms.
1C.M., Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA, UK. c.murdoch@sheffield.ac.uk.
Kornchanok
K
Wayakanon
Martin H
MH
Thornhill
C W Ian
CW
Douglas
Andrew L
AL
Lewis
Nicholas J
NJ
Warren
Abigail
A
Pinnock
Steven P
SP
Armes
Giuseppe
G
Battaglia
Craig
C
Murdoch
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016866:Bacteroidaceae Infections / Q000188:drug therapy*; D002478:Cells, Cultured; D004318:Doxycycline / Q000008:administration & dosage / Q000627:therapeutic use; D005881:Gingiva / Q000382:microbiology / Q000473:pathology; D005882:Gingival Diseases / Q000188:drug therapy*; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology*; D008795:Metronidazole / Q000008:administration & dosage / Q000627:therapeutic use; D053769:Nanocapsules / Q000737:chemistry; D010518:Periodontitis / Q000188:drug therapy; D011108:Polymers / Q000737:chemistry; D016966:Porphyromonas gingivalis / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D053769:Nanocapsules; D011108:Polymers; D008795:Metronidazole; D004318:Doxycycline
antimicrobial chemotherapy; nanotechnology; periodontal disease