title: Biodegradable nanofibrous drug delivery systems: effects of metronidazole and ciprofloxacin on periodontopathogens and commensal oral bacteria.
abstract: OBJECTIVE
  The purposes of this study were to fabricate biodegradable polydioxanone (PDS II®) electrospun periodontal drug delivery systems (hereafter referred to as matrices) containing either metronidazole (MET) or ciprofloxacin (CIP) and to investigate the effects of antibiotic incorporation on both periodontopathogens and commensal oral bacteria.
  
  
  METHODS
  Fibrous matrices were processed from PDS polymer solution by electrospinning. Antibiotic-containing PDS solutions were prepared to obtain four distinct groups: 5 wt.% MET, 25 wt.% MET, 5 wt.% CIP, and 25 wt.% CIP. Pure PDS was used as a control. High-performance liquid chromatography (HPLC) was done to evaluate MET and CIP release. Dual-species biofilms formed by Lactobacillus casei (Lc) and Streptococcus salivarius (Ss) were grown on the surface of all electrospun matrices. After 4 days of biofilm growth, the viability of bacteria on biofilms was assessed. Additionally, antimicrobial properties were evaluated against periodontopathogens Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa) using agar diffusion assay.
  
  
  RESULTS
  A three-dimensional interconnected porous network was observed in the different fabricated matrices. Pure PDS showed the highest fiber diameter mean (1,158 ± 402 nm) followed in a descending order by groups 5 wt.% MET (1,108 ± 383 nm), 25 wt.% MET (944 ± 392 nm), 5 wt.% CIP (871 ± 309 nm), and 25 wt.% CIP (765 ± 288 nm). HPLC demonstrated that groups containing higher amounts (25 wt.%) of incorporated drugs released more over time, while those with lower levels (5 wt.%) the least. No inhibitory effect of the tested antibiotics was detected on biofilm formation by the tested commensal oral bacteria. Meanwhile, CIP-containing matrices inhibited growth of Fn and Aa.
  
  
  CONCLUSIONS
  CIP-containing matrices led to a significant inhibition of periodontopathogens without negatively impairing the growth of periodontal beneficial bacteria.
  
  
  CONCLUSIONS
  Based on the proven in vitro inhibition of periodontitis-related bacteria, future in vivo research using relevant animal models is needed to confirm the effectiveness of these drug delivery systems.
authors.affiliation: Department of Restorative Dentistry, Division of Dental Biomaterials, Indiana University School of Dentistry (IUSD), 1121 W. Michigan Street, Indianapolis, IN, 46202, USA, mbottino@iu.edu.
authors.forename: Marco C
authors.initials: MC
authors.lastname: Bottino
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Arthur
authors.forename: R Aaron
authors.initials: RA
authors.lastname: Waeiss
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kamocki
authors.forename: Karen S
authors.initials: KS
authors.lastname: Gregson
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gregory
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems; D016967:Fusobacterium nucleatum / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007780:Lacticaseibacillus casei / Q000187:drug effects; D008795:Metronidazole / Q000008:administration & dosage / Q000494:pharmacology*; D057139:Nanofibers; D010518:Periodontitis / Q000188:drug therapy* / Q000382:microbiology*; D016687:Polydioxanone; D013291:Streptococcus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D008795:Metronidazole; D016687:Polydioxanone; D002939:Ciprofloxacin