In Vitro Evaluation of Antimicrobial Activity of Minocycline Formulations for Topical Application in Periodontal Therapy

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....

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Main Authors: Jan-Luca Schmid, Martin Kirchberg, Sandra Sarembe, Andreas Kiesow, Anton Sculean, Karsten Mäder, Mirko Buchholz, Sigrun Eick
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/12/4/352
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author Jan-Luca Schmid
Martin Kirchberg
Sandra Sarembe
Andreas Kiesow
Anton Sculean
Karsten Mäder
Mirko Buchholz
Sigrun Eick
author_facet Jan-Luca Schmid
Martin Kirchberg
Sandra Sarembe
Andreas Kiesow
Anton Sculean
Karsten Mäder
Mirko Buchholz
Sigrun Eick
author_sort Jan-Luca Schmid
collection DOAJ
description 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 (P<sub>503</sub>-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.
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spelling doaj.art-d7ff464fa7884dafb36d4e1676e757432023-11-19T21:30:32ZengMDPI AGPharmaceutics1999-49232020-04-0112435210.3390/pharmaceutics12040352In Vitro Evaluation of Antimicrobial Activity of Minocycline Formulations for Topical Application in Periodontal TherapyJan-Luca Schmid0Martin Kirchberg1Sandra Sarembe2Andreas Kiesow3Anton Sculean4Karsten Mäder5Mirko Buchholz6Sigrun Eick7Laboratory of Oral Microbiology, Department of Periodontology, School of Dental Medicine, University of Bern, CH-3010 Bern, SwitzerlandInstitute of Pharmacy, Martin-Luther University Halle, D-06120 Halle (Saale), GermanyCharacterization of Medical and Cosmetic Care Products, Fraunhofer Institute for Microstructures and Materials IMWS, D-06120 Halle/Saale, GermanyCharacterization of Medical and Cosmetic Care Products, Fraunhofer Institute for Microstructures and Materials IMWS, D-06120 Halle/Saale, GermanyDepartment of Periodontology, School of Dental Medicine, University of Bern, CH-3010 Bern, SwitzerlandInstitute of Pharmacy, Martin-Luther University Halle, D-06120 Halle (Saale), GermanyDrug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology IZI-MWT and PerioTrap Pharmaceuticals GmbH, D-06120 Halle/Saale, GermanyLaboratory of Oral Microbiology, Department of Periodontology, School of Dental Medicine, University of Bern, CH-3010 Bern, SwitzerlandPeriodontal 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 (P<sub>503</sub>-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.https://www.mdpi.com/1999-4923/12/4/352controlled releaseperiodontitislocal antibioticsin vitro modelgingival flow
spellingShingle Jan-Luca Schmid
Martin Kirchberg
Sandra Sarembe
Andreas Kiesow
Anton Sculean
Karsten Mäder
Mirko Buchholz
Sigrun Eick
In Vitro Evaluation of Antimicrobial Activity of Minocycline Formulations for Topical Application in Periodontal Therapy
Pharmaceutics
controlled release
periodontitis
local antibiotics
in vitro model
gingival flow
title In Vitro Evaluation of Antimicrobial Activity of Minocycline Formulations for Topical Application in Periodontal Therapy
title_full In Vitro Evaluation of Antimicrobial Activity of Minocycline Formulations for Topical Application in Periodontal Therapy
title_fullStr In Vitro Evaluation of Antimicrobial Activity of Minocycline Formulations for Topical Application in Periodontal Therapy
title_full_unstemmed In Vitro Evaluation of Antimicrobial Activity of Minocycline Formulations for Topical Application in Periodontal Therapy
title_short In Vitro Evaluation of Antimicrobial Activity of Minocycline Formulations for Topical Application in Periodontal Therapy
title_sort in vitro evaluation of antimicrobial activity of minocycline formulations for topical application in periodontal therapy
topic controlled release
periodontitis
local antibiotics
in vitro model
gingival flow
url https://www.mdpi.com/1999-4923/12/4/352
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