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

A new local delivery device (LDD) capable of releasing silver in periodonta l pockets has been developed and tested pre-clinically. Silver has potent a ntimicrobial effects on Gram-negative periodontal pathogens with a mean in vitro minimum bactericidal concentration (MBC) less than or equal to0.5 mug /ml, This phase 1 study assessed the safety, pharmacokinetics and bioavaila bility of silver ions delivered intracrevicularly with a resorbable LDD(Poc ketGuard (TM)) in a group of 9 volunteers affected with periodontitis. In e ach subject, a PLGA/PEG LDD loaded with 12% silver nitrate (w/w) was insert ed in each of 4 selected pockets greater than or equal to5 mm. Serum. gingi val fluid and subgingival plaque samples were evaluated before and at vario us time points after LDD placement for 21 days. At each time point. the con centration of silver in gingival crevicular fluid (GCF) was quantified with an Inductively Coupled Plasma-Mass Spectrometer. Subgingival plaque sample s were processed for evaluation of total anaerobic and aerobic counts (CFU/ ml). The maximum mean silver concentration in GCF was 1493 +/- 709 mug/ml ( range 589-2245). It decayed exponentially with a half-life of 7.1 +/- 6.1 d ays (2.7-20.4). Average silver concentrations in excess of 10 mug/ml were d etected in each patient For 14 days after LDD placement with the average co ncentration for all patients in excess of 25 mug/mL at day 21, Total anaero bic counts decreased an average of 1.7 +/- 1.9 x 10(6) 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 spontaneo usly could be removed at the end of the study with polishing. No systemic e ffects were observed. It is concluded that local silver concentrations abov e the MBC in serum were maintained for at least 21 days. A specific microbi ologic effect was also observed,