K. Wayakanon, M. Thornhill, I. Douglas, G. Battaglia, and C. Murdoch (UK)
Drug delivery, Nanomaterials, Intracellular infection andOral tissue mucosa
Symptoms of periodontitis are gingivitis and destruction of tooth-supporting bones leading to tooth loss. Porphyromonas gingivalis can invade and reside in human keratinocytes and is associated periodontitis. Metronidazole is used to treat periodontitis; however, this antibiotic is impermeable to the human plasma membrane and cannot kill intracellular P.gingivalis, which may then re-infect the periodontal pocket. Polymersomes are nano sized amphiphilic polymer vesicles that can encapsulate hydrophilic molecules in their cores and hydrophobic molecules within membranes. Cells take polymersomes up by endocytosis into lysosomes where they are disrupted by the low pH leading to intracellular release of their drug-load. Objectives: Studying the effectiveness of polymersomes to deliver antibiotics to kill intracellular P.gingivalis. Methods: Monolayers of normal oral keratinocytes, keratinocyte cell lines or tissue-engineered oral mucosa were invaded with P.gingivalis. Intracellular P.gingivalis was visualised by confocal microscopy and immunohistochemistry staining. P.gingivalis-infected keratinocytes and tissue-engineered oral mucosa were treated with polymersome-encapsulated metronidazole, free metronidazole, or polymersome alone and the number of surviving intracellular P.gingivalis measured by antibiotic protection assay. Results: Intracellular P.gingivalis was observed in keratinocytes. Polymersome encapsulated metronidazole significantly reduced levels of intracellular bacteria (p<0.05). Conclusion: Polymersomes are effective antibiotic delivery vehicles that kill intracellular P.gingivalis and could potentially be used to treat recurrent periodontitis.
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