Chlorhexidine Chip.

The chlorhexidine chip is a small chip (4.0 × 5.0 × 0.35 mm) that contains 2.5 mg of the active ingredient chlorhexidine gluconate in a resorbable, biodegradable matrix of hydrolyzed gelatin, cross-linked with glutaraldehyde, packaged in individual foil containers (Figure 89-1, A). It is indicated as an adjunct to SRP procedures for the reduction of pocket depth (PD) in patients with adult periodontitis and may be used as part of a periodontal maintenance program, which includes good oral hygiene and SRP.⁸⁰ After placement in the pocket, the chip has been reported to release chlorhexidine into the gingival crevicular fluid (GCF) over 7 to 10 days.⁹⁶ Chlorhexidine is active against a broad range of microbes, disrupting the cell membrane and causing precipitation of the cytoplasm, resulting in cell death. No adverse alterations within the oral microbial flora or overgrowth of opportunistic microorganisms have been observed.⁸⁰ The chip is biodegradable and does not require removal, but dental floss should be avoided for 10 days to avoid dislodging the chip. The chip is stored at 20° to 25° C (68° to 77° F), with excursions permitted to 15° to 30°C (59° to 86°F). The chlorhexidine chip is placed into the pocket directly from the foil container using a forceps (Figure 89-1, B).

Doxycycline Gel.

The doxycycline gel is a subgingival controlled-release delivery product composed of a two-syringe mixing system (Figure 89-2, A). Syringe A contains 450 mg of a bioabsorbable polymeric formulation of 36.7% poly(D,L,-lactide) dissolved in 63.3% N-methyl-2-pyrrolidone. Syringe B contains 50 mg of doxycycline hyclate, equivalent to 42.5 mg doxycycline. The two syringes are stored at 2° to 30° C (36° to 86° F). When mixed, the constituted product is a viscous liquid of 500 mg, which contains 50 mg (10%) doxycycline hyclate. The doxycycline gel is indicated for the treatment of chronic adult periodontitis for a gain in clinical attachment, reduction in probing depth, and reduction of bleeding on probing.⁸ Doxycycline, a broad-spectrum semisynthetic tetracycline, is bacteriostatic, inhibiting bacterial protein biosynthesis by interfering with transfer RNA (tRNA) and messenger RNA (mRNA) at the ribosome. No overgrowth of opportunistic organisms was observed following use of the doxycycline gel.⁸ The gel has been reported to release doxycycline within the GCF over 7 days.¹⁰³ The doxycycline gel is biodegradable and does not require removal. If not used immediately, the mixed contents in syringe A may be stored at room temperature for a maximum of 3 days within an airtight container. The doxycycline gel is used by injecting the mixed contents of the two syringes directly into the pocket (Figure 89-2, B). The pocket contents are then covered with either a periodontal dressing or a cyanoacrylate dental adhesive.

Minocycline Microspheres.

The minocycline microspheres product is a subgingival controlled-release delivery system containing the antibiotic minocycline hydrochloride incorporated into a bioresorbable poly(glycolide-co-D,L-lactide) polymer in unit-dose cartridges (Figure 89-3). Each cartridge delivers minocycline hydrochloride equivalent to 1 mg of minocycline free base. The minocycline microspheres are indicated as an adjunct to SRP for reduction of PD in patients with adult periodontitis and as part of a periodontal maintenance program, which includes good oral hygiene and SRP.⁶ Minocycline belongs to the tetracycline class of antibiotics and has a broad spectrum of activity. Its bacteriostatic, antimicrobial activity results from the inhibition of protein biosynthesis. No overgrowth of opportunistic microorganisms was noted during clinical studies. No changes in the presence of minocycline-resistant bacteria, Candida albicans or Staphylococcus aureus, in the gastrointestinal tract were detected at the end of a 56-day study, although there was a slight increase in the numbers of minocycline-resistant bacteria in periodontal pocket plaque samples after 9 months.⁶ The clinical significance of the changes is unknown. Patients should avoid hard or sticky foods at the treated teeth for 1 week and interproximal cleaning devices for about 10 days. The minocycline microspheres formulation is biodegradable and does not require removal. The cartridges are stored at 20° to 25° C (68° to 77° F), with excursions permitted to 15° to 30° C (59° to 86° F). Excessive heat should be avoided. The minocycline microspheres are used by injecting the contents of a unit-dose cartridge into the pocket. Neither a periodontal dressing nor an adhesive are needed.

For complete details for the use of locally delivered, controlled-release antimicrobial products, including a discussion of the safety profiles, the reader is referred to the full prescribing information for each product.6,8,80

Chlorhexidine Chip.

The release profile of the chlorhexidine chip was evaluated in a single-center, 10-day clinical trial in 19 patients with chronic adult periodontitis.⁹⁶ Each patient received a single chip administered into each of four pocket sites, and concentrations of chlorhexidine were determined in GCF, plasma, and urine at various times post dosing. Peak GCF concentrations were achieved 2 hours postdose (2007 ± 422 µg/mL), with GCF concentrations maintained between approximately 1300 and 1900 µg/mL to 4 days postdose. Mean chlorhexidine concentrations then steadily decreased to 57 ± 13 µg/mL at 9 days. Chlorhexidine was below detectable limits in plasma and urine at all time points. For perspective, Wilson et al¹⁰⁸ reported that chlorhexidine, at a concentration of 125 µg/mL, killed 99.9% of cultivable bacteria from plaque samples from patients with chronic periodontitis within 15 minutes.

Doxycycline Gel.

The release profile of the doxycycline gel was evaluated in a single-center, 28-day clinical trial in 32 patients with adult periodontitis and compared with oral doxycycline.¹⁰³ All patients assigned to receive local delivery had doxycycline gel administered to all pocket sites with probing depth 5 mm or more that bled on probing; drug was retained after placement either with a noneugenol (NE) periodontal dressing (n = 13) or 2-octyl cyanoacrylate (2-O; n = 13). Mean GCF concentrations peaked at 2 hours after dosing (1473 ± 328 µg/mL, NE; 1986 ± 445 µg/mL, 2-O). At day 7, mean concentrations were 309 ± 127 µg/mL (NE) and 148 ± 49 µg/mL (2-O). Mean salivary concentrations peaked at 2 hours (4.05 ± 1.24 µg/mL, NE; 8.78 ± 1.48 µg/mL, 2-O) and were ≤ 2 µg/mL at 24 hours. Serum concentrations following local administration remained ≤ 0.1 µg/mL. With regard to oral doxycycline (200 mg on day 0, then 100 mg/day for 7 days; n = 6), GCF concentrations peaked at 12 hours postdose (2.53 ± 1.56 µg/mL), and serum concentrations ranged from 0.91 to 2.26 µg/mL for the 8 days of data collection. Salivary concentrations never exceeded 0.11 µg/mL.

Minocycline Microspheres.

The release profile of minocycline microspheres was studied in 18 patients with moderate to advanced chronic periodontitis.6,7 Minocycline microspheres (mean dose: 46.2 mg; 25 to 112 unit doses) were administered to eligible periodontal pocket sites 5 mm or more in probing depth (minimum of 30 sites on at least eight teeth; 1 mg per treatment site) following SRP. Serum and saliva samples were collected predose and at various times postdose to 14 days. Mean dose-normalized saliva area under the curve and maximal concentration (C_max) were approximately 125 and 1000 times that of serum parameters, respectively. In saliva minocycline, C_max was 254.0 ± 139.3 mg/mL at 0.75 ± 0.56 hours postdose with a half-life of 44.7 ± 19.2 hours.⁷ In serum mean minocycline concentrations peaked at 4.8 ± 1.8 hours postdose (C_max: 216.4 ± 122.9 µg/mL) and were undetectable by 7 days. Minocycline concentrations in saliva and GCF were sufficient (defined as >1 µg/mL) to kill bacteria associated with periodontal disease in vitro.⁷ These concentrations were evident up to 14 days without significant systemic exposure.⁷