Abstract
Periodontal therapy using antimicrobials that are topically applied requires slow or controlled release devices. The in vitro antimicrobial activity of biodegradable polymer formulations that contain a new minocycline lipid complex (P-MLC) was evaluated. The new P-MLC formulations that contained 11.5% minocycline were compared with pure minocycline or an existing commercial formulation, which included determination of minimal inhibitory concentration (MIC) values against two oral bacteria and activity on six-species periodontal biofilm. Moreover, the flow of gingival crevicular fluid (GCF) was modeled up to 42 days and the obtained eluates were tested both for MIC values and inhibiting biofilm formation. In general, MICs of the P-MLC formulations were slightly increased as compared with pure minocycline. Biofilm formation was clearly inhibited by all tested formulations containing minocycline with no clear difference between them. In 3.5 day old biofilms, all formulations with 250 µg/mL minocycline decreased bacterial counts by 3 log10 and metabolic activity with no difference to pure antimicrobials. Eluates of experimental formulations showed superiority in antimicrobial activity. Eluates of one experimental formulation (P503-MLC) still inhibited biofilm formation at 28 days, with a reduction by 1.87 log10 colony forming units (CFU) vs. the untreated control. The new experimental formulations can easily be instilled in periodontal pockets and represent alternatives in local antimicrobials, and thus warrant further testing.
Highlights
Periodontal disease is associated with an imbalance of microorganisms in subgingival biofilm
Systemic antibiotics improve the clinical outcomes, their use should be restricted to severe cases [5], as antimicrobial use affects the gut microbiota [6] and is clearly associated with global development of antimicrobial resistance [7]
The wells of a 96-well-plate were coated with 10 μL/well for 1 h, before 10 μL/well phosphate buffered saline (PBS) with 1.5% bovine serum albumin (PBS/SA) was added for 10 min followed by the mixed bacterial suspension in Wilkins–Chalgren broth with 5% of lysed horse blood and 5 μg/mL β-NAD
Summary
Periodontal disease is associated with an imbalance of microorganisms in subgingival biofilm. Topical antimicrobials combined with mechanical therapy can improve the clinical outcome [8] This is underlined by a systemic review including more than 50 studies, in which the effect was most pronounced in deep and residual pockets [12]. The new formulations show higher stability in an aqueous environment as compared with the pure drug molecules [22] This is an important aspect, as drug molecules in biodegradable PLGA polymers could be exposed to a very acidic aqueous microenvironment (pH 2) for longer times prior to their release [23]. All strains were precultured on tryptic soy agar plates (Oxoid, Basingstoke, GB) with 5% sheep blood for 24 h at 37 °C with the respective conditions (S. gordonii, A. naeslundii with 10% CO2, others anaerobically). After an incubation time of 18 h (anaerobes 42 h) in respective atmosphere, the MIC was assessed as the lowest concentration without visible growth (turbidity)
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