Effects of an acidic calcium phosphate solution and the intraoral fluoride-releasing device on dental caries and fluoride uptake in rats.

This investigation comprised two studies evaluating the effects of an acidic calcium phosphate solution (CPS) on fluoride uptake in the enamel, glycolysis of dental plaque, the incidence of dental caries and urinary fluoride concentrations of rats wearing an intraoral fluoride-releasing device (IFRD). In the first study, CPS-fluoride treatment preceded the cariogenic challenge. In the second study, the cariogenic challenge preceded the treatments. In the first study, CPS treatments increased the ability of enamel to bind fluoride. However, the enamel-bound fluoride exerted a negligible effect on plaque glycolysis as measured by the pH decrease after sucrose challenge. In the second study CPS augmented the caries inhibition for both the sulcal-morsal and buccal-lingual surfaces. In both studies the IFRD significantly restricted the development of carious enamel on the sulcal-morsal surfaces and caused elevated concentrations of fluoride in the urine independent of CPS treatments.

Development and in vitro evaluation of an intra-oral controlled-release delivery system for chlorhexidine.

Copolymers of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) were prepared and used to fabricate a membrane-controlled reservoir-type controlled-release delivery system for chlorhexidine that should be suitable for intra-oral use. The reservoir of the system was prepared by softening an 80:20 mixture of chlorhexidine diacetate and 50:50 HEMA:MMA copolymer with methyl ethyl ketone (MEK), and pressing standard amounts of the resulting dough-like mixture into silicone rubber molds. A membrane was applied to the reservoirs by rotating them through a solution of 30:70 HEMA:MMA copolymer in MEK. The finished oval-shaped controlled-release pellets were approximately 4.7 mm wide, 3.3 mm high, and 7.4 mm long, and contained 45.0 +/- 3.7 mg of chlorhexidine diacetate. The mean in vitro release rate of chlorhexidine diacetate from the pellets into 37 degrees C water was 608 +/- 55 micrograms/24 h for days 2 through 11, and 389 +/- 50 micrograms/24 h for days 15 to 30 of the test period. The chlorhexidine released on day 30 was biologically active, as determined by a serial dilution assay against Streptococcus mutans. The extended release of biologically active chlorhexidine at a controlled rate from this system suggests that it is worthy of further evaluation for the intra-oral therapy of chlorhexidine-treatable oral infections in non-compliant and physically or mentally compromised individuals.

Effects of octenidine on dental plaque and gingivitis in monkeys.

This investigation monitored the effects of daily oral rinses with octenidine on plaque and gingivitis in five monkeys. Formulations containing 0.5% or 1.0% octenidine or the rinse vehicle placebo were provided daily for 2 weeks. Each week the dentition of each monkey was examined, photographed, and sampled for plaque. All responses exhibited a numerical decrease in mean scores following treatments with each concentration of octenidine, whereas the placebo treatment exerted negligible effects. Decreases in plaque mass were observed after 2 weeks of treatment with 1% octenidine (58%) or 0.5% octenidine (55%) compared with the corresponding baseline values. Similar trends were noted in the extent and thickness of supragingival plaque and its ability to decrease the pH of a sucrose solution. Octenidine treatments reduced the proportions of motile forms in samples of subgingival plaque and also restricted its ability to produce H2S. Slight numerical decreases were seen in the Gingival Index and flow rate of the crevicular fluid. These consistent protective trends suggest that octenidine decreases the pathogenic potential of established plaque.

Evaluation of an intraoral controlled release delivery system for fluoride in primates.

An intraoral delivery system designed to release 0.5 mg of fluoride per day was evaluated in short-term studies in primates. This fluoride-releasing device, bonded to the buccal surface of the maxillary right central incisor of each of six monkeys (Macaca fascicularis), produced marked elevations in saliva and plaque fluoride concentrations without increases in serum fluoride concentrations. No changes were observed in the plaque and gingival scores or the populations of various species of plaque bacteria.

Inhibition of experimental dental caries using an intraoral fluoride-releasing device.

An intraoral fluoride releasing device designed to provide continual topical fluoride therapy for the prevention of dental caries was found to be effective in inhibiting caries in the rat model. Animals fitted with an intraoral device that released approximately 0.15 mg of fluoride per day developed 63% fewer carious enamel areas than animals receiving no treatment. Fluoridated drinking water (10 ppm) produced a 25% reduction in carious enamel areas. The fluoride-releasing device was more effective than ad libitum fluoridated drinking water in inhibiting caries on the approximal and sulcal surfaces. These results agree with the hypothesis that the continual presence of fluoride in oral fluids enhances the cariostatic effect of fluoride and, when combined with the results of earlier primate and human trials of the intraoral fluoride-releasing device, suggest that this fluoride delivery system can be developed into an effective anticaries agent.

Clinical evaluation of an intraoral device for the controlled release of fluoride.

An intraoral-releasing device designed to release 0.5 mg of fluoride per day was evaluated in a one-month trial. The results showed that the 11 men who wore the fluoride-releasing device on their maxillary first molars had significantly elevated levels of fluoride in their saliva and plaque compared with baseline levels. No significant changes were observed in mean serum or urine fluoride levels or in the gingival or plaque indexes during the study. The prevalence of S mutans in whole saliva did not change during the study and the relative proportion of S. mutans, S. sanguis, and A viscosus and A naeslundii in plaque also remained relatively stable. The elevated fluoride levels in saliva and plaque are presumptive evidence that the intraoral fluoride-releasing device could exert a cariostatic effect in humans. However, long-term clinical trials are needed to determine the cariostatic potential of this fluoride releasing system.

The use of controlled and sustained release agents in dentistry: a review of applications for the control of dental caries.

Three types of sustained and controlled release dosage forms of sodium fluoride (NaF) for the prevention of dental caries are reviewed. Sustained release NaF tablets or capsules have prolonged the elevation of saliva and plasma fluoride levels in both animal and human studies when compared to conventional NaF tablets. In vitro studies have shown that aerosol application of NaF-containing microcapsules to the tooth surface may prolong the retention of a given dose of fluoride in the mouth and also increase enamel uptake of fluoride. A membrane-controlled reservoir-type intra-oral controlled release device for NaF is potentially the most effective dosage form of NaF developed to date. Devices releasing 0.02 to 1.0 mg of fluoride per day for 30 to 180 days have been prepared. Extensive testing has shown that the devices function under both in vitro and in vivo conditions and the device has been approved by the US Food and Drug administration for preliminary testing in humans.

The evaluation of tiodonium chloride as an antiplaque and anticaries agent. III. Evaluation of the antiplaque potential of tiodonium chloride utilizing a rat model.

Tiodonium chloride (4-chlorophenyl-2-thienyliodonium chloride), when used in a twice daily mouthrinse at a concentration of 0.3% for either one or four weeks, inhibited dental plaque formation in rats that had been inoculated with Streptococcus mutans 6715-15 and Actinomyces viscosus T-6. Mouthrinses containing 0.1 and 0.2% tiodonium chloride were also effective in inhibiting plaque, but not as consistently as the 0.3% level.

8-Hydroxyquinolines with the potential for long-term anticaries activity: design, synthesis, and in vitro evaluation.

8-Hydroxyquinolyl benzoate and 8-hydroxyquinolyl para-(fluorosulfonyl)benzoate have been synthesized and evaluated in vitro as antimicrobial and antiplaque agents. Both compounds inhibited the growth of cultures of the following genera: Streptococcus, Staphylococcus, Actinomyces, Lactobacillus, Veillonella, and Candida. Minimum inhibitory concentrations ranged from 0.98 to 62 microgram/ml. Extracted human teeth pretreated with 1% solutions of either compound and rinsed with distilled water exhibited reduced in vitro plaque formation for 48 hours. These results indicate that the in vitro antiplaque activity of 8-hydroxyquinolines can be enhanced by attaching the appropriate side chain in the 8-position.

Alkylamine salts and amides: in vitro inhibition of S mutans 6715.

Our studies with the salts and amides of alkylamines have shown that the undecylenate salts have significant in vitro activity against S mutans No 6715, suggesting that these agents are worthy of additional evaluation. The attempt to increase activity by combining undecylenic acid with the alkylamines was not successful; however, better attachment to tooth surfaces and/or retention during washing did occur. Our results suggest that the free amino group of alkylamines and the free acid group of undecylenic acid are required for these two classes of agents to demonstrate antibacterial activity.

Catechol O-methyltransferase. 8. Structure-activity relationships for inhibtion by 8-hydroxyquinolines.

A series of 5- and 7-substituted 8-hydroxyquinolines was evaluated as inhibitors of catechol O-methyltransferase (COMT, E.C. 2.1.1.6). The electronic character of the substituents in the 5 position appeared to have only a small effect if any on the inhibitory activity of these compounds. A significant factor which contributes to the inhibitory activity of these compounds appears to be the nature of the 7-substituent. The structure-activity relationship for this series of inhibitors is discussed relative to the nature of the enzymatic binding site.

Synthesis and in vitro evaluation of 8-hydroxyquinoline analogs as inhibitors of dental plaque.

A group of 5-substituted 8-hydroxyquinolines with predicted log P values in the 1-4 range has been prepared from either 8-hydroxyquinoline or its appropriate derivative. 5-Formyl-, 5-iodo-, 5-fluoro-, 5-acetyl-, and 5-methoxymethyl-8-hydroxyquinoline in addition to methyl-5(8-hydroxyquinolyl)acetate and ethyl 5-(8-hydroxyquinolyl)acetate displayed greater in vitro antiplaque activity than 8-hydroxyquinoline.

A physiochemical approach to the study of amines as antiplaque agents.

Alkyl and aromatic amines were evaluated for inhibitory activity against S mutans 6715. Only the alkylamines were active and this may be due to their greater basicity. The agents that showed good activity were decylamine, dodecylamine, tetradecylamine, and hexadecylamine. In addition to the free bases, the hydrochloride and hydrofluoride salts were also tested for inhibitory activity and the same four agents were shown to be most active. These agents appear to hold good promise as antiplaque agents against S mutans 6715, therefore, further in vitro studies against other plaque-forming bacteria and toxicological and clinical evaluation seems to be warranted to determine the best clinical agent.