betadex and Periodontitis

This clinical trial compared the efficacy of doxycycline (DOX) in β-cyclodextrin (DOX)/βCD) with DOX- alone in gel on thirty-three subjects with periodontitis. Patients were randomized to group 1 GI; 10% DOX + scaling and root planning (SRP); group 2 (GII (10% DOX /β-CD + SRP), and group 3 (GIII; SRP). Gels were applied in GI and GII at baseline (T0) and 30 days later (T1). Periodontal Probing Depth (PPD), Clinical Attachment Level (CAL), Bleeding on Probing (BOP) and Visible Plaque Index (VPI) were evaluated at (T0), 30 days (T1) and 60 days after T0 (T2). Bone density was analyzed after 18 months (T3). GII showed the most significant reduction of PPD (2.62 mm; p <0.003), and greatest gain in CAL (2.54 mm p <0.003) at T2. BOP and the VPI had a strong reduction in all groups at T2 (p <0.05), both decreased by ≥5 times and 2 times, respectively, in all groups at T1. Bone density increased in all groups in radiographs (T3). The use of DOX encapsulated in β-CD gel with SRP resulted in significant improvements in clinical periodontal parameters; such molecular inclusion of doxycycline into β-CD in gel for local application is relatively simple and useful in dentistry.

Topics: Adult; Anti-Bacterial Agents; beta-Cyclodextrins; Dental Plaque Index; Dental Scaling; Double-Blind Method; Doxycycline; Drug Compounding; Female; Gels; Humans; Male; Middle Aged; Periodontal Attachment Loss; Periodontal Index; Periodontitis; Root Planing; Treatment Outcome; Young Adult

Dental implants of ciprofloxacin beta-cyclodextrin inclusion complex were formulated using poly (epsilon-caprolactone), a biodegradable polymer and evaluated. Clinical evaluation was carried out in ten patients with acute peridontitis. Various clinical parameters, viz. gingival index, plaque score, attachment gain, reduction in pocket depth were evaluated at 10, 20, 30, 40 days of treatment and compared with placebo as control. A significant (P < 0.0001) improvement in the healing of periodontal pockets treated with ciprofloxacin beta-cyclodextrin implant was observed in most of the clinical parameters. Estimation of gingival crevicular fluids (GCF) for the drug content revealed that drug levels above the minimum inhibitory concentration (10.2 micrograms/mg) for many of the periodontal pathogens were maintained throughout the period of study (40 days). This confirms the clinical efficacy of the dose and the duration of the study. It was found that biodegradable carrier was better accepted than the non-biodegradable carriers reported earlier.

Topics: Adult; Anti-Infective Agents; beta-Cyclodextrins; Ciprofloxacin; Cyclodextrins; Dental Implants; Dental Materials; Drug Implants; Humans; Periodontitis

This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (βCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis.. Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-βCD (ligature), and 25 mg/kg of αTPN-βCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy.. The treatment with αTPN-βCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-βCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis.. The results obtained suggest that the treatment with αTPN-βCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-βCD.

Topics: Alveolar Bone Loss; Animals; beta-Cyclodextrins; Cyclohexane Monoterpenes; Female; Ligation; Periodontitis; Rats

Periodontitis treatments usually require local administration of antimicrobial drugs with the aim to reduce the bacterial load inside the periodontal pocket. Effective pharmaceutical treatments may require sustained local drug release for several days in the site of interest. Currently available solutions are still not able to fulfill the clinical need for high-quality treatments, mainly in terms of release profiles and patients' comfort. This work aims to fill this gap through the development of an in situ gelling system, capable to achieve controlled and sustained release of antimicrobial agents for medium-to-long-term treatments. The system is composed of micrometer-sized β-cyclodextrin-based hydrogel (bCD-Jef-MPs), featured by a strong hydrophilic character, suspended in a synthetic block-co-polymer solution (Poloxamer 407), which is capable to undergo rapid thermally induced sol-gel phase transition at body temperature. The chemical structure of bCD-Jef-MPs was confirmed by cross-correlating data from Fourier transform infrared (FTIR) spectroscopy, swelling test, and degradation kinetics. The thermally induced sol-gel phase transition is demonstrated by rheometric tests. The effectiveness of the described system to achieve sustained release of antimicrobial agents is demonstrated in vitro, using chlorhexidine digluconate as a drug model. The results achieved in this work disclose the potential of the mentioned system in effectively treating periodontitis lesions.

Topics: 3T3-L1 Cells; Animals; Anti-Infective Agents; beta-Cyclodextrins; Delayed-Action Preparations; Hydrogels; Mice; Periodontitis; Periodontium; Poloxamer

Antimicrobial peptides (AMPs) have shown rapid and potent effect against planktonic bacteria. However, control of periodontopathic biofilms is a challenge even for AMPs. Thus, the present study evaluates in vitro antimicrobial activity of synthetic peptide LyeTxI and association compound LyeTxI/β-cyclodextrin (βCD) against multispecies biofilms.. Sensibility to LyeTxI and LyeTxI/βCD was determined for planktonic Gram-negative periodontopathogens. Time-kill kinetic assay was performed at minimum inhibitory concentrations (MICs) in all planktonic strains. Multispecies biofilms were grown on pegs using a biofilm device and studied by scanning electron microscopy at 2, 5, and 10 days. Minimal biofilm eradication concentration (MBEC) was determined for 2- and 4-day multispecies biofilms. Metabolic activity of biofilms was determined by fluorometry study.. Biofilms showed reproducible cell density on pegs of the biofilm device. LyeTxI and LyeTxI/βCD were active against all strains tested at concentrations ≤62.5 μg/mL. Kinetic assays showed rapid bactericidal effect of LyeTxI against all periodontopathogens. MBECs of LyeTxI and LyeTxI/βCD against multispecies 2-day biofilms were two-fold higher than MICs of cells shed from biofilms. LyeTxI was able to reduce multispecies 2-day metabolic activity by 90%. Multispecies 4-day biofilms were tolerant to all agents tested.. LyeTxI and LyeTxI/βCD are active against periodontopathic bacteria, showing rapid bactericidal effect and may be used to prevent biofilm development. In the future, AMPs could be therapeutic tools for treatment of periodontitis.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; beta-Cyclodextrins; Biofilms; Gram-Negative Bacteria; Humans; Kinetics; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Periodontitis

Host cell invasion is important for periodontal pathogens in evading host defenses and spreading into deeper areas of the periodontal tissue. Treponema denticola has been implicated in a number of potentially pathogenic processes, including periodontal tissue penetration. Here we tested the ability of T. denticola strains to invade human gingival epithelial cells (HGEC). After 2 h infection, intracellular location of T. denticola cells was confirmed by confocal laser scanning microscopy (CLSM). Results from an antibiotic protection assay following [(3)H]uridine labeling indicated that invasion efficiency reached a maximum at 2 h after infection. Internalized T. denticola cells were still observed in HGEC at 24 h by CLSM. A dentilisin deficient mutant exhibited significantly decreased invasion (p < 0.05) compared with the wild-type strain. In inhibition assays, phenylmethylsulfonyl fluoride and metabolic inhibitors such as methyl-β-cyclodextrin and staurosporine significantly reduced T. denticola invasion. Under CLSM, T. denticola colocalized with GM-1 ganglioside-containing membrane microdomains in a cholesterol-dependent manner. These results indicated that T. denticola has the ability to invade into and survive within HGECs. Dentilisin activity of T. denticola and lipid rafts on HGEC appear to play important roles in this process.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Cyclodextrins; Cell Line; Cell Membrane; Epithelial Cells; Gingiva; Host-Parasite Interactions; Humans; Membrane Microdomains; Microbial Sensitivity Tests; Peptide Hydrolases; Periodontitis; Phenylmethylsulfonyl Fluoride; Spirochaetales Infections; Staurosporine; Treponema denticola

Local host-modulation therapy is an emerging approach to prevent disease progression in sites with moderate periodontitis. The combination of simvastatin and alendronate would be an intriguing host-modulatory strategy because of the bone-anabolic properties of simvastatin and the antiresorptive/bone-targeting characteristics of alendronate. The objective of this study was to evaluate the effects of local administration of a simvastatin-alendronate-β-cyclodextrin (SIM-ALN-CD) conjugate for preventing experimental periodontitis bone loss.. Twenty-four mature female Sprague-Dawley rats were treated with three, 12 μL injections, administered one week apart, bilaterally into the palatal/interproximal gingiva. The injections contained: (i) a conjugate of 0.5 mg of SIM and 3.75 mg of ALN-CD in H2 O; (ii) H2 O alone; or (iii) no treatment. One week later, the same sites were subjected to induction of experimental periodontitis by three injections (i.e. one injection administered every other day for five d) of 0.01 mg of Escherichia coli endotoxin [lipopolysaccharide (LPS)] in phosphate-buffered saline (PBS) or PBS alone. After an additional week, the rats were killed, the palates were harvested and interproximal bone volume and adjacent thickness were calculated using microcomputed tomography. Subsequently, specimens were decalcified, and interproximal histologic sections were stained with hematoxylin and eosin for evaluation of alveolar crest osteoclasts and surrounding inflammation. Values were compared among treatment groups using analysis of variance and the Kruskal-Wallis test.. Interproximal bone volume was reduced by LPS injections (p ≤ 0.04), yet when experimental periodontitis was preceded by treatment with SIM-ALN-CD, more bone was preserved than after treatment with carrier alone (p = 0.007). While LPS caused a significant loss in bone thickness over the palatal roots (p ≤ 0.04), the injection protocol (PBS) also caused a significant loss of palatal bone thickness (p ≤ 0.03). However, prophylactic SIM-ALN-CD injections resulted in no further loss of bone thickness during experimental periodontitis. LPS injections gave histologic evidence of increased osteoclasts and subsulcular inflammation, both of which were reduced when preceded by treatment with SIM-ALN-CD (p ≤ 0.0002).. The primary conclusion of this study was that locally applied SIM-ALN-CD has the potential to prevent episodes of periodontitis bone loss.

Topics: Alendronate; Alveolar Bone Loss; Animals; beta-Cyclodextrins; Bone Density Conservation Agents; Drug Combinations; Endotoxins; Escherichia coli; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imaging, Three-Dimensional; Injections; Lipopolysaccharides; Maxillary Diseases; Molar; Osteoclasts; Palate; Periodontitis; Premedication; Rats; Rats, Sprague-Dawley; Sequestering Agents; Simvastatin; X-Ray Microtomography