Metronidazole-loaded bioabsorbable films as local antibacterial treatment of infected periodontal pockets.
BACKGROUND
Periodontal disease is infectious in nature and leads to an inflammatory response. It arises from the accumulation of subgingival bacterial plaque and leads to the loss of attachment, increased probing depth, and bone loss. It is one of the world's most prevalent chronic diseases. In this study we developed and studied metronidazole-loaded 50/50 poly(DL-lactide-co-glycolide) (PDLGA), 75/25 PDLGA, and poly(DL-lactic acid) (PDLLA) films. These films are designed to be inserted into the periodontal pocket and treat infections with controlled-release metronidazole for >or=1 month.


METHODS
The structured films were prepared using the solution-casting technique. Concentrated solutions and high solvent-evaporation rates were used to get most of the drug located in the bulk, i.e., in whole film's volume. The effects of copolymer composition and drug content on the release profile, cell growth, and bacterial inhibition were investigated.


RESULTS
The PDLLA and 75/25 PDLGA films generally exhibited a low- or medium-burst release followed by a moderate release at an approximately constant rate, whereas the 50/50 PDLGA films exhibited a biphasic release profile. The drug released from films loaded with 10% weight/weight metronidazole resulted in a significant decrease in bacterial viability within several days. When exposed to human gingival fibroblasts in cell culture conditions, these films maintained their normal fibroblastic features.


CONCLUSIONS
This study enabled the understanding of metronidazole-release kinetics from bioabsorbable polymeric films. The developed systems demonstrated good biocompatibility and the ability to inhibit Bacteroides fragilis growth; therefore, they may be useful in the treatment of periodontal diseases.
Shifrovitch
Yael
Y
Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel.
Binderman
Itzhak
I
Bahar
Hila
H
Berdicevsky
Israela
I
Zilberman
Meital
M
D020341:Absorbable Implants; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage*; D001442:Bacteroides Infections / Q000188:drug therapy; D001441:Bacteroides fragilis / Q000187:drug effects*; D002478:Cells, Cultured; D004343:Drug Implants / Q000138:chemical synthesis / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008422:Materials Testing; D008795:Metronidazole / Q000008:administration & dosage*; D008826:Microbial Sensitivity Tests; D010514:Periodontal Pocket / Q000188:drug therapy* / Q000382:microbiology; D011091:Polyesters / Q000138:chemical synthesis / Q000633:toxicity; D011098:Polyglactin 910 / Q000138:chemical synthesis / Q000633:toxicity
D000891:Anti-Infective Agents, Local; D004343:Drug Implants; D011091:Polyesters; D008795:Metronidazole; D011098:Polyglactin 910; C033616:poly(lactide)