Release of metronidazole from electrospun poly(L-lactide-co-D/L-lactide) fibers for local periodontitis treatment.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Conservative Dentistry, Jena University Hospital, Friedrich-Schiller-Universität Jena, Germany. markusreise@gmail.com
Markus
M
Reise
Ralf
R
Wyrwa
Ulrike
U
Müller
Matthias
M
Zylinski
Andrea
A
Völpel
Matthias
M
Schnabelrauch
Albrecht
A
Berg
Klaus D
KD
Jandt
David C
DC
Watts
Bernd W
BW
Sigusch
D020341:Absorbable Implants; D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002152:Calorimetry, Differential Scanning; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004058:Diffusion; D016503:Drug Delivery Systems / Q000295:instrumentation*; D055664:Electrochemical Techniques; D005347:Fibroblasts / Q000187:drug effects; D016967:Fusobacterium nucleatum / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008422:Materials Testing; D008795:Metronidazole / Q000008:administration & dosage* / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D010518:Periodontitis / Q000188:drug therapy*; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D016966:Porphyromonas gingivalis / Q000187:drug effects; D013052:Spectrometry, X-Ray Emission; D013499:Surface Properties; D013997:Time Factors
D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011091:Polyesters; D008795:Metronidazole; C033616:poly(lactide)