Release of metronidazole from electrospun poly(l-lactide-co-d/l-lactide) fibers for local periodontitis treatment

Reise, Markus; Wyrwa, Ralf; Müller, Ulrike; Zylinski, Matthias; Völpel, Andrea; Schnabelrauch, Matthias; Berg, Albrecht; Jandt, Klaus D.; Watts, David C.; Sigusch, Bernd W.

doi:10.1016/j.dental.2011.12.006

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Volume 28, Issue 2 , Pages 179-188, February 2012

Release of metronidazole from electrospun poly(l-lactide-co-d/l-lactide) fibers for local periodontitis treatment

Markus Reise
- Department of Conservative Dentistry, Jena University Hospital, Friedrich-Schiller-Universität Jena, Germany
- Corresponding author at: Schlossgasse 2, 07743 Jena, Germany. Tel.: +49 151 40417944.
Ralf Wyrwa
- Department of Biomaterials, INNOVENT e.V., Jena, Germany
Ulrike Müller
- Department of Biomaterials, INNOVENT e.V., Jena, Germany
Matthias Zylinski
- Department of Conservative Dentistry, Jena University Hospital, Friedrich-Schiller-Universität Jena, Germany
Andrea Völpel
- Department of Conservative Dentistry, Jena University Hospital, Friedrich-Schiller-Universität Jena, Germany
Matthias Schnabelrauch
- Department of Biomaterials, INNOVENT e.V., Jena, Germany
Albrecht Berg
- Department of Biomaterials, INNOVENT e.V., Jena, Germany
Klaus D. Jandt
- Institute of Materials Science and Technology (IMT), Friedrich-Schiller-University Jena, Germany
David C. Watts
- Institute of Materials Science and Technology (IMT), Friedrich-Schiller-University Jena, Germany
- University of Manchester, School of Dentistry, Manchester M15 6FH, UK
Bernd W. Sigusch
- Department of Conservative Dentistry, Jena University Hospital, Friedrich-Schiller-Universität Jena, Germany

Received 18 July 2011; received in revised form 10 December 2011; accepted 11 December 2011.

Abstract

Objectives

We aimed to achieve detailed biomaterials characterization of a drug delivery system for local periodontitis treatment based on electrospun metronidazole-loaded resorbable polylactide (PLA) fibers.

Methods

PLA fibers loaded with 0.1–40% (w/w) MNA were electrospun and were characterized by SEM and DSC. HPLC techniques were used to analyze the release profiles of metronidazole (MNA) from these fibers. The antibacterial efficacy was determined by measuring inhibition zones of drug-containing aliquots from the same electrospun fiber mats in an agar diffusion test. Three pathogenic periodontal bacterial strains: Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were studied. Cytotoxicity testing was performed with human gingival fibroblasts by: (i) counting viable cells via live/dead staining methods and (ii) by exposing cells directly onto the surface of MNA-loaded fibers.

Results

MNA concentration influenced fiber diameters and thus w/w surface areas: diameter being minimal and area maximal at 20% MNA. HPLC showed that these 20% MNA fibers had the fastest initial MNA release. From the third day, MNA release was slower and nearly linear with time. All fiber mats released 32–48% of their total drug content within the first 7 days. Aliquots of media taken from the fiber mats inhibited the growth of all three bacterial strains. MNA released up to the 28th day from fiber mats containing 40% MNA significantly decreased the viability of F. nucleatum and P. gingivalis and up to the 2nd day also for the resistant A. actinomycetemcomitans. All of the investigated fibers and aliquots showed excellent cytocompatibility.

Significance

This study shows that MNA-loaded electrospun fiber mats represent an interesting class of resorbable drug delivery systems. Sustained drug release properties and cytocompatibility suggest their potential clinical applicability for the treatment of periodontal diseases.

Keywords: Electrospun fibers, Polymeric fibers, Metronidazole, Biomaterials, Polylactide, Periodontitis, Drug delivery system, Dental materials