Increased prevalence of oral diseases such as gingivitis, periodontitis and dental caries has become major health issue worldwide. Such growing incidence of periodontitis has directly affected the development of drug delivery systems and growth of the market. Since the infections are limited to periodontal pockets or oral cavity, localized intrapocket drug delivery will be more beneficial than conventional systemic administration. Advances in intrapocket technology and innovations in the field of periodontal drug delivery led to increased patent applications. Newer trends like use of mucoadhesive polymers, in situ forming gels, viscosity modifiers, plasticizers etc which can enhance intrapocket retention of drugs have gained considerable attention among researchers and industrialists. Current market is flooded with products such as Periostat, Periochip(®), Atridox(®), Arestin(®), Actisite(®), Dentomycin(®), and Elyzol(®) and generics such as metronidazole, levofloxacin, tetracycline, doxycyline and minocycline for intrapocket delivery. There is a need of novel drugs and delivery systems with better efficacy profiles than the existing compounds. Inclusion of novel technologies like films, fibers, in situ forming implants, microparticles, nanoparticles, and liposomes as intrapocket drug delivery has great potential. Development of antibiotic free drug delivery such as antiseptics, host modulators, biofilms inhibitors and antibodies has promising role in the improvement of pathogenesis of periodontitis. Further, this review deals with various innovations in drug delivery and patents related to localized intrapocket administration of medicaments in the implications of periodontitis.

The purpose of the present study was to evaluate the effects of tetracycline fibres (TCF) as an adjunct to scaling in the treatment of generalised aggressive periodontitis and to compare the effects with mechanical treatment only. Ten patients, 24-39 years old referred for treatment to the Department of Preventive Dentistry, Periodontology and Implant Biology, Aristotle University of Thessaloniki took part in the study. A split-mouth experimental design was used. Measurements referring to bleeding on probing (BOP), pocket depth (PD) and clinical attachment level (CAL) were performed at 12 sites randomly selected. Clinical recordings were made at baseline, 2 and 6 months, after treatment. Subgingival plaque samples were taken for microbiological analysis using the 'checkerboard' DNA-DNA hybridisation technique at baseline, immediately after treatment and at 2 and 6 months. Full-mouth scaling and root planing were performed, with the exception of 2 pre-selected sites, which served as controls. Tetracycline fibres were applied in 5 pockets located in the same half mouth. Analysis of clinical findings showed that mechanical instrumentation in combination with TCF application led to a greater improvement in clinical parameters than scaling and root planing only. Microbial analysis showed a statistically significant greater reduction in the percentages of detection for B. forsythus, P. nigrescens and A. naeslundii genospecies II in pockets where tetracycline fibres were applied. In conclusion, the clinical and microbiological data of the present study suggest that the adjunctive use of TCF improves the clinical response of scaling and root planing in aggressive periodontitis patients.

Antimicrobial agents, systemic and/or local, are thought by some to be effective agents for treating periodontal infections. Here the authors determine the costs and benefits of local delivery agents for treating periodontal disease. Applying this cost-benefit analysis to patient care, however, will depend upon a clinician's expertise and a patient's value system.

The management of periodontal diseases has included both non-surgical and surgical treatment options. Non-surgical treatment traditionally has referred to the role of mechanical instrumentation of the root surface with either scalers or curettes. However, the introduction of locally delivered anti-microbial medications, which can be placed directly into a periodontal pocket, has provided the practitioner with another treatment option. This article looks at the different locally delivered anti-microbial medications being used in the non-surgical management of periodontal diseases.

Electrospun fiber mats are explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. The mats were made either from poly(lactic acid) (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two. The fibers were electrospun from chloroform solutions containing a small amount of methanol to solubilize the drug. The release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV-VIS spectroscopy. Release profiles from the electrospun mats were compared to a commercially available drug delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast films of the various formulations.

This article discusses the principles, products, and techniques currently available for local delivery of antimicrobials in the treatment of adult periodontitis. Four principles provide the scientific basis for the treatment of periodontitis: it is caused by bacteria; it cannot be cured, but it can be controlled; clinicians cannot remove all the plaque and calculus; and periodontitis reinfects. This article stresses how the local delivery of antimicrobials can help the clinician achieve the goals of arresting the disease and maintaining the disease in the arrested or controlled state. Rationales for reevaluating the treated patient and treatment options are presented. Local-delivery systems are reviewed, stressing those available in the United States. Pharmacokinetics, multicenter randomized trials, and techniques are presented.

In situ release kinetics of 25% tetracycline-loaded fibers (Actisite) were evaluated in this study. 1 cm precut tetracycline fibers were removed from periodontal pockets (>5 mm) of 24 patients. Fibers were maintained at their site for 1, 3, 7, 10 and 12 days. Remaining biologically active tetracycline on the fibers was determined by agar diffusion inhibition assay. Inhibition zones induced by fibers on P. gingivalis (256) seeded BHI agar were measured after 48 hours of anaerobic incubation. Data were evaluated by one-way analysis of variance with Post-hoc Duncan analysis. Results of this study show there is a considerable decrease in the amount of tetracycline remaining in the fibers removed between 1-3 and 10-12 days. The amount of active drug remaining in the fibers at days 3 and 7 was comparable and indicates no significant deposition between these two days.

To longitudinally determine if early therapeutic intervention, based on a positive neutral protease activity (NPA) assay score could effectively arrest the progress of periodontal disease destruction.

Periodontal therapy has the primary aim of halting periodontal disease progression. Clinical trials over the years have indicated that meticulous scaling and root planing in conjunction with a patient's proper plaque control can arrest periodontitis, but this therapy is not always completely effective and thus adjunctive therapies need to be considered. Local delivery of antibacterial agents into periodontal pockets has been extensively developed and investigated since the late 1970s and many systems have been designed to maintain high levels of antimicrobial agents in the crevicular fluid with minimal systemic uptake. More recently subgingival antimicrobial delivery systems have become available to the practising periodontist for clinical use. These systems, employ different antimicrobial agents but also different delivery systems which influence the concentration of available drug over time. The dental profession is confused by the wide variety of available slow release subgingival antimicrobial devices on the market and clearly comparative independent assessment of these therapies is needed. This review will summarise the findings of a comparative study on three commonly available periodontal local delivery antimicrobial systems on sites with previously unsuccessful mechanical therapy. The slow release devices studied adjunctively with root planing were: Actisite, Dentomycin and Elyzol, compared to root planing alone. Substantivity of an antimicrobial system is the ability of the system to maintain an effective concentration of drug over time which may be the most significant difference between the three delivery systems rather than the type of antimicrobial drug used. Although all three locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone, a treatment regime of scaling and root planing plus tetracycline fibre placement gave the greatest reduction in probing pocket depth over the six months after treatment.

The purpose of this study was to investigate the clinical, microbiological and radiological effects of peri-implantitis therapy by local delivery of tetracycline. In 25 partially edentulous patients, 30 implants with radiographic evidence of circumferential bone loss, and peri-implant probing depths > or =5 mm were treated with polymeric tetracycline HCl-containing fibers. Clinical and microbial parameters were recorded at baseline, and 1, 3, 6, and 12 months (M) after treatment. Standardized radiographs were obtained at baseline, M3, and one year after treatment. Two patients were discontinued from the study after 180 days because of persisting active peri-implantitis with pus formation. The remaining subjects showed a significant decrease of mean peri-implant probing depth from 6.0 to 4.1 mm (M1, P<0.001), which was maintained over 12 months. In comparison to baseline, the bleeding tendency was significantly reduced after one month, and thereafter (P<0.001). No significant recession of the mucosal margin was noted. The radiologically determined distance from the shoulder of the implant to the bottom of the bony defect decreased slightly, but not significantly, from 5.2 to 4.9 mm. At M1, M3 and M6, mean total anaerobic cultivable bacterial counts were significantly lower than at baseline (P<0.001). A significant decrease in frequency of detection was noted for Prevotella intermedia/nigrescens, Fusobacterium sp., Bacteroides forsythus, and Campylobacter rectus (P<0.01). Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Eikenella corrodens had very low baseline frequencies that could not be significantly suppressed further. In conclusion, therapy of peri-implantitis by local delivery of tetracycline had a positive effect on clinical and microbiological parameters.

A clinical and microscopical (SEM) investigation has been carried out on the biocompatibility of cellulose acetate fiber tetracycline with 25% of tetracycline hydrochloride (Actisite R). A subject with advanced periodontal disease was selected and a pocket of 8 mm of PD was chosen. A segment of fiber was inserted into the pocket for 8 days. After removal, PD and GI clinical parameters were detected and the fiber removed was analyzed at the scanning electronic microscope. The results showed clinical signs of inflammation after removal of fiber. SEM analysis showed macrophagic reaction, a typical sign of inflammatory response to material. The study suggests the need of more biocompatible materials, easier to use as delivery system of antibiotics in the treatment of periodontal disease.

The aims of the present study were to assess radiographically the effects of scaling/root planing combined with antibiotic therapy using tetracycline fibers (TCF): (I) on alveolar bone density and linear descriptors and (II) on supracrestal soft tissue density. 19 subjects with generalized adult periodontitis (with at least 20 teeth present, at least 4 teeth with pockets >4 mm and bleeding upon controlled force probing) and high cultural counts of Porphyromonas gingivalis were recruited from a pool of 57 patients. The full mouth treatment group (FT) consisted of 10 patients, who underwent a full mouth supra-gingival scaling and prophylaxis treatment and were instructed to rinse 2x daily with a 0.1% chlorhexidine solution. 1 week later, tetracycline-hydrochloride-containing fibers (Actisite periodontal fiber) were applied around all teeth. After 7-12 days, the fibers were removed and all teeth were scaled and root planed under local anaesthesia. The chlorhexidine rinsing continued for another 2 months. In 9 subjects (local treatment group LT), 2 teeth with periodontal lesions with pocket probing pepth (PPD) > or =5 mm were treated by placement of tetracycline fibers, which remained in place for 7 to 12 days. Upon removal of the fibers, scaling and root planing was performed on these 2 teeth, while the rest of the dentition remained untreated, and no chlorhexidine rinse was applied. 2 of the untreated teeth revealing similar periodontal lesions were chosen to represent sites affected by untreated periodontitis (NT). In this group, a limited local treatment was performed (2 teeth) with the inherent potential for recolonization from the untreated pocket sites. Standardized periapical radiographs were obtained from the 4 monitored sites within each patient at baseline (before treatment) and 2 and 6 months thereafter. One radiograph was exposed in a standard way for bone assessment. The second radiograph was underexposed, at about a 1/5 of the original exposure time to allow the evaluation of soft tissue. Mean changes in the linear parameters and changes in density (CADIA) observed at multiple sites within each patient and treatment group were used as the best estimate of treatment outcome. Over the observation period of 6 months, a significant difference in bone height changes was found between the untreated sites (median loss -0.29 mm) and the sites from full-mouth treated patients (median gain 0.24 mm, p=0.008). When comparing the baseline to the 6 months radiographs, a loss in bone density was observed for the untreated group (median=-2.13 CADIA). Both treatment groups revealed a gain in density (median=1.58 and 2.43 CADIA for the locally and the full-mouth treated groups, respectively). Differences in density were significant, both between the nontreated and locally treated sites (p=0.026) and between the nontreated sites and the sites from the full mouth treated patients (p=0.002). The analysis of the soft tissues showed a similar pattern of changes in density to those seen in the bone defect. At 2 months, there was a tendency for loss in density for the nontreated group (median=-0.17 CADIA) that continued over the 6 month period (median=-0.31 CADIA). A significant increase in density was observed for the full-mouth treated sites (median=1.57 and 0.64 CADIA for the 2 and 6 months radiographs, respectively). A significant increase was also observed for the locally treated group when compared to the untreated sites (median=0.13 and 0.10 CADIA for the 2 and 6 months radiographs, respectively). Comparing untreated sites with full-mouth treated sites, a significant difference was observed for CADIA measurements (p<0.001). No significant difference was observed comparing locally treated and untreated sites (p=0.24). It was concluded that scaling and root planing combined with TCF therapy can result in increased bone density and alveolar bone height. Full-mouth treatment seemed to result in more pronounced gains compared to local tre

With the introduction of Actisite (tetracycline hydrochloride) periodontal fiber therapy, controlled drug delivery of tetracycline into the periodontal pocket has become a clinical reality. An important factor in the success of this treatment option is the selection of suitable candidates according to specific patient selection criteria proposed by the author in this article. Case reports describing periodontal tetracycline fiber therapy, used adjunctively with conventional mechanical therapy and oral hygiene, document the reductions in pocket depth and bleeding upon probing over a six-month follow-up period, suggesting the value of this therapy in maintaining the periodontal health of patients who meet the selection criteria.

The purpose of this study was to determine the clinical response to local delivery of tetracycline in relation to clinical and microbiological conditions of the other teeth. 4 deep pockets were monitored in 19 subjects with multiple deep periodontal lesions and high counts of P. gingivalis. In 9 patients (LT) only 2 of the selected lesions were treated by placement of tetracycline fibers (Actisite), while the rest of the dentition was left untreated. In the other 10 patients, all teeth were supragingivally scaled and then treated by application of polymeric tetracycline HCl containing fibers, the whole dentition was subject to full mouth scaling and root planing, and the patients rinsed with 0.2% chlorhexidine (FT). A significant reduction in mean PPD was observed in all treated sites after two months. This reduction was maintained over the following 4 months. The magnitude of the effect was significantly greater in the FT group (1.74 mm) than in the LT group (0.88 mm). The mean attachment level changes were similar after 2 months in locally and fully treated subjects. A tendency of relapse was noted for treated sites in LT patients from month 2 to 6. A level of statistical significance was not reached for this effect. Data from measurements recorded at 6 sites around all teeth in the full mouth treated patients were analyzed using multiple linear regression. This analysis showed local changes in PPD and AL were significantly and strongly correlated with the baseline value of the respective parameter at the same site. In addition, more pocket depth reduction was noted if a site was not bleeding on probing at 6 months, if the location of a site was not approximal and if the tooth was not a second molar. Sites located on second molars showed also less AL gain than sites located on other teeth. Smokers showed significantly less reduction in PPD and significantly less AL gain. Furthermore, if subjects had a high % of pockets deeper than 4 mm at baseline they showed significantly less attachment gain.

Actisite (tetracycline hydrochloride) periodontal fiber is a 23 cm monofilament containing 12.7 mg tetracycline HCl homogeneously dispersed in a polymer. This product is indicated as an adjunct to scaling and root planing to reduce pocket depth and bleeding on probing in patients with adult periodontitis. The sustained-release system, placed in the periodontal pocket for 10 d, releases the antibiotic through mechanisms of diffusion and osmosis. A study was conducted in 13 patients with moderate to severe adult periodontitis to evaluate the amount of tetracycline HCl released during therapy (based on residual drug content). Fibers placed in the pocket remained in place for an average of 9 d. Each patient had 1-4 teeth treated with fiber therapy. At the termination of therapy samples from 29 teeth were retrieved and analyzed. The amount of matrix polymer was used as an internal standard for the quantitation of tetracycline, eliminating any uncertainties with respect to recovery or contamination. An average of 31% (SD 9%) of the tetracycline HCl content was released from the fiber during the treatment period. No single fiber had less than 50% of the original drug remaining. The study demonstrated that a substantial amount of the tetracycline remains in the Actisite fiber at removal (about 70%), which indicates that substantial drug concentrations are maintained in the pocket for the duration of treatment.

The purpose of this study was to determine the distribution of black-pigmenting Gram-negative bacteria in the dentition of 10 adult periodontitis patients before and after treatment by local delivery of tetracycline. The subjects were selected based on a screening for high counts of Porphyromonas gingivalis and multiple deep pockets. Subgingival microbial samples were taken from the mesial and distal aspect of every tooth (44 to 56 sites per patient) before treatment, and after one and two months. Therapy included full mouth scaling and root planing, chlorhexidine mouth rinsing and placement of tetracycline HCl fibers (Actisite) on all teeth. 63.4% of 524 baseline samples yielded total anaerobic viable counts > or = 10(6) CFU/ml; P. gingivalis was found in 59.2% and Prevotella intermedia in 56.9%. One month after treatment, the % of samples with > or = 10(6) CFU/ml was reduced to 9.4%, 5.3% were P. gingivalis- and 5.1% P. intermedia- positive. After 2 months, 9.6% samples yielded > or = 10(6) CFU/ml, 5.2% were P. gingivalis- and 9.4% P. intermedia- positive. 20 of the 39 sites with a persistence of P. gingivalis were located on second molars. Logistic regression models were utilized to explain the persistence of P. gingivalis, using site location and other clinical parameters as independent variables. These analyses indicated a strong association of site location, pocket depth and bleeding on sampling with persistence of P. gingivalis. The study shows that local delivery of tetracycline is highly effective in reducing the prevalence and proportions of black-pigmenting anaerobes within a dentition. Bleeding deep pockets of second molars have an increased risk for persistence of these anaerobes.

Development of new drug therapy is difficult for large companies and almost unheard of by individuals. This autobiographical account of the development of the tetracycline fiber delivery system for periodontal therapy (Actisite) relates experiences of a scientist between 1976 and 1994 which lead to FDA approval. In this account, the author acknowledges some of the key people, companies and institutions who were important in this development, makes observations concerning the process itself and offers suggestions for those who might consider commercial development of a scientific concept.

Treatment with the tetracycline HCL-containing (Actisite infinity) fiber has been shown to improve clinical measures of periodontitis, as well as reduce the number of sites infected with putative periodontal pathogens. In this study, we examined the effect of the tetracycline fiber on biochemical mediators of the host's inflammatory response in gingival crevicular fluid (GCF). The total amount of the lysosomal enzyme beta-glucuronidase (beta G), considered a marker of primary granule release from polymorphonuclear leukocytes and interleukin-1 beta, a cytokine with important proinflammatory effects, were examined in GCF. Patients with localized recurrent periodontitis were followed over a 16 week period. Treated teeth (Tx), teeth adjacent to treated teeth (ADJ) and control teeth (Cx) were studied. Following fiber therapy, the Tx teeth displayed statistically significant reductions in mean probing depth, depth of the deepest site and bleeding on probing over the 16 weeks of the trial. Significant reduction in the depth of the deepest site was also seen for the ADJ teeth over 16 weeks. Total beta G in GCF was reduced for the Tx teeth comparing baseline to 16 weeks, but no significant changes were observed for the ADJ or Cx teeth. Prior to treatment, total beta G for the Tx teeth was 211 +/- 49 U (mean +/- standard error), versus 146 +/- 174 U for the ADJ teeth and 121 +/- 33 U for the Cx teeth. 16 weeks treatment, the mean values for these 3 categories of teeth were comparable (Tx = 95 +/- 20 U, ADJ = 93 +/- 42 U and Cx = 103 +/- 29 U). For the Tx teeth, the maximum reduction in total beta G following therapy occurred at 6 weeks (65%). Total IL-1 beta was significantly reduced for the Tx teeth at 3 and 6 weeks, but rebounded at 16 weeks. In contrast to what was seen for beta G, the maximum reduction in total IL-1 beta for the Tx teeth was observed at 3 weeks (68%). These data suggest that host mediators associated with increased risk for active disease are reduced following tetracycline fiber therapy. Future studies will determine the relative importance of a reduced microbial challenge versus a tetracycline-mediated direct modification of the host response to account for the reduction in the host inflammatory response in GCF following tetracycline fiber therapy.

This article addresses the use of tetracycline-impregnated fibers in the treatment of periodontal diseases. Clinical and microbiologic data are reviewed to provide pragmatic guidelines for fiber use. In addition, controversial issues associated with the labeling of Actisite, the potential of developing antibiotic-resistant strains, and the benefits of systemic vs local drug delivery are discussed. Ultimately, the article concludes that tetracycline-impregnated fibers can be used as an adjunct to scaling and root planing in certain patients at sites that do not respond to conventional therapy.

Thirty-one patients with chronic adult periodontitis participated in this long-term private practice study. Sixty-one sites with moderate (4-6 mm, n = 21) or deep (> or = 7 mm, n = 40) periodontal pockets and bleeding on probing were treated with an antibiotic-releasing fiber, Actisite (Periodontal Therapeutic System) (tetracycline hydrochloride). Scaling/root planing (SRP) was performed on all teeth 3 weeks before start of the study, and on most teeth immediately before fiber insertion. Monolithic fibers loaded with 25% tetracycline hydrochloride were inserted in periodontal pockets, where they were retained for a mean of 6.7 days, at which point they were removed. Patients were evaluated at 1, 3, and 6 months after treatment; subgroups were also evaluated at normalized 12-month (10 patients, 20 sites) and 24-month (13 patients, 20 sites) time points. Sites showed a mean probing depth reduction of 2.5 mm at 6 months, and 2.2 mm at 24 months, with the deepest sites showing the greatest reduction. Bleeding on probing was 100% at baseline, 34% at 3 months, and 50% at 6 months. Attachment gains in 18 patients (25 sites) were 2.4 mm at 1 month, 3.0 mm at 3 months, and 2.5 mm at 6 months. Fibers were well tolerated; no adverse effects from treatment were noted. These results indicate that use of tetracycline fiber plus SRP clearly reduced the clinical signs of periodontal disease and maintained or improved attachment for up to 24 months in sites previously refractory to treatment.