Phase 1 evaluation of a local delivery device releasing silver ions in periodontal pockets: safety, pharmacokinetics and bioavailability

• Published in: Journal of periodontal research Vol. 36; no. 3; pp. 187 - 193
• Main Authors: Straub, A. M., Suvan, J., Lang, N. P., Mombelli, A., Braman, V., Massaro, J., Friden, P., Tonetti, M. S.
• Format: Journal Article
• Language: English
• Published: Copenhagen Munksgaard International Publishers 01-06-2001; Blackwell
• Subjects: Absorbable Implants; Anti-Infective Agents, Local - administration & dosage; Anti-Infective Agents, Local - analysis; Anti-Infective Agents, Local - blood; Anti-Infective Agents, Local - pharmacokinetics; Bacteria, Aerobic - drug effects; Bacteria, Aerobic - growth & development; Bacteria, Anaerobic - drug effects; Bacteria, Anaerobic - growth & development; Biocompatible Materials; Biological and medical sciences; Biological Availability; clinical trial; Colony Count, Microbial; Dental Plaque - chemistry; Dental Plaque - microbiology; Drug Delivery Systems; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Female; Gingival Crevicular Fluid - chemistry; gingival fluid; Humans; local delivery; Male; Mass Spectrometry; Medical sciences; Middle Aged; Non tumoral diseases; Otorhinolaryngology. Stomatology; Periodontal Pocket - drug therapy; pharmacokinetics; Polyethylene Glycols; Polyglactin 910; Safety; silver; Silver Nitrate - administration & dosage; Silver Nitrate - analysis; Silver Nitrate - blood; Silver Nitrate - pharmacokinetics; Statistics as Topic; Tooth Discoloration - chemically induced; Tooth Root - drug effects; Human; Delivery system; Stomatology; Device; Parodontium; Bioavailability; Periodontal disease; Treatment; Equipment; Periodontitis; Clinical trial; Silver ion; Safety; Pharmacokinetics; Gram negative bacteria
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1034/j.1600-0765.2001.360308.x

A new local delivery device (LDD) capable of releasing silver in periodontal pockets has been developed and tested pre‐clinically. Silver has potent antimicrobial effects on Gram‐negative periodontal pathogens with a mean in vitro minimum bactericidal concentration (MBC) ≤0.5 μg/ml. This phase 1 study assessed the safety, pharmacokinetics and bioavailability of silver ions delivered intracrevicularly with a resorbable LDD (PocketGuardTM) in a group of 9 volunteers affected with periodontitis. In each subject, a PLGA/PEG LDD loaded with 12% silver nitrate (w/w) was inserted in each of 4 selected pockets ≥5 mm. Serum, gingival fluid and subgingival plaque samples were evaluated before and at various time points after LDD placement for 21 days. At each time point, the concentration of silver in gingival crevicular fluid (GCF) was quantified with an Inductively Coupled Plasma‐Mass Spectrometer. Subgingival plaque samples were processed for evaluation of total anaerobic and aerobic counts (CFU/ml). The maximum mean silver concentration in GCF was 1493±709 μg/ml (range 589–2245). It decayed exponentially with a half‐life of 7.1±6.1 days (2.7–20.4). Average silver concentrations in excess of 10 μg/ml were detected in each patient for 14 days after LDD placement with the average concentration for all patients in excess of 25 μg/mL at day 21. Total anaerobic counts decreased an average of 1.7±1.9×106 CFU/ml (p=0.0078) from baseline to day 7, indicating that the silver was biologically active. A mild increase in cervical root discoloration was observed at day 21: 0.25±0.31 stain index units. Discoloration that did not resolve spontaneously could be removed at the end of the study with polishing. No systemic effects were observed. It is concluded that local silver concentrations above the MBC in serum were maintained for at least 21 days. A specific microbiologic effect was also observed.