Sustained-release Varnish Research Articles

Polyglactin 910 Meshes Coated with Sustained-Release Cannabigerol Varnish Inhibit Staphylococcus aureus Biofilm Formation and Macrophage Cytokine Secretion: An In Vitro Study.

Synthetic surgical meshes are commonly used in abdominal wall reconstruction surgeries to strengthen a weak abdominal wall. Common mesh-related complications include local infection and inflammatory processes. Because cannabigerol (CBG) has both antibacterial and anti-inflammatory properties, we proposed that coating VICRYL (polyglactin 910) mesh with a sustained-release varnish (SRV) containing CBG would prevent these complications. We used an in vitro infection model with Staphylococcus aureus and an in vitro inflammation model of lipopolysaccharide (LPS)-stimulated macrophages. Meshes coated with either SRV-placebo or SRV-CBG were exposed daily to S. aureus in tryptic soy medium (TSB) or macrophage Dulbecco's modified eagle medium (DMEM). Bacterial growth and biofilm formation in the environment and on the meshes were assessed by changes in optical density, bacterial ATP content, metabolic activity, crystal violet staining, spinning disk confocal microscopy (SDCM), and high-resolution scanning electron microscopy (HR-SEM). The anti-inflammatory effect of the culture medium that was exposed daily to the coated meshes was analyzed by measuring the release of the cytokines IL-6 and IL-10 from LPS-stimulated RAW 264.7 macrophages with appropriate ELISA kits. Additionally, a cytotoxicity assay was performed on Vero epithelial cell lines. We observed that compared with SRV-placebo, the segments coated with SRV-CBG inhibited the bacterial growth of S. aureus in the mesh environment for 9 days by 86 ± 4% and prevented biofilm formation and metabolic activity in the surroundings for 9 days, with respective 70 ± 2% and 95 ± 0.2% reductions. The culture medium that was incubated with the SRV-CBG-coated mesh inhibited LPS-induced secretion of IL-6 and IL-10 from the RAW 264.7 macrophages for up to 6 days without affecting macrophage viability. A partial anti-inflammatory effect was also observed with SRV-placebo. The conditioned culture medium was not toxic to Vero epithelial cells, which had an IC50 of 25 µg/mL for CBG. In conclusion, our data indicate a potential role of coating VICRYL mesh with SRV-CBG in preventing infection and inflammation in the initial period after surgery.

Sinonasal Stent Coated with Sustained-Release Varnish of Mometasone Furoate Inhibits Pro-Inflammatory Cytokine Release from Macrophages: An In Vitro Study

The aim of the study was to develop a sustained-release varnish (SRV) containing mometasone furoate (MMF) for sinonasal stents (SNS) to reduce mucosa inflammation in the sinonasal cavity. The SNS' segments coated with SRV-MMF or an SRV-placebo were incubated daily in a fresh DMEM at 37 °C for 20 days. The immunosuppressive activity of the collected DMEM supernatants was tested on the ability of mouse RAW 264.7 macrophages to secrete the cytokines' tumor necrosis factor α (TNFα) and interleukin (IL)-10 and IL-6 in response to lipopolysaccharide (LPS). The cytokine levels were determined by respective Enzyme-Linked Immunosorbent Assays (ELISAs). We found that the daily amount of MMF released from the coated SNS was sufficient to significantly inhibit LPS-induced IL-6 and IL-10 secretion from the macrophages up to days 14 and 17, respectively. SRV-MMF had, however, only a mild inhibitory effect on LPS-induced TNFα secretion as compared to the SRV-placebo-coated SNS. In conclusion, the coating of SNS with SRV-MMF provides a sustained delivery of MMF for at least 2 weeks, maintaining a level sufficient for inhibiting pro-inflammatory cytokine release. This technological platform is, therefore, expected to provide anti-inflammatory benefits during the postoperative healing period and may play a significant role in the future treatment of chronic rhinosinusitis.

Improved Anti-Biofilm Effect against the Oral Cariogenic Streptococcus mutans by Combined Triclosan/CBD Treatment

Streptococcus mutans is a Gram-positive bacterium highly associated with dental caries, and it has a strong biofilm-forming ability, especially in a sugar-rich environment. Many strategies have been undertaken to prevent dental caries by targeting these bacteria. Recently, we observed that a sustained-release varnish containing triclosan and cannabidiol (CBD) was more efficient than each compound alone in preventing biofilm formation by the fungus Candida albicans, which is frequently involved in oral infections together with S. mutans. It was therefore inquiring to study the effect of this drug combination on S. mutans. We observed that the combined treatment of triclosan and CBD had stronger anti-bacterial and anti-biofilm activity than each compound alone, thus enabling the use of lower concentrations of each drug to achieve the desired effect. The combined drug treatment led to an increase in the SYTO 9low, propidium iodide (PI)high bacterial population as analyzed by flow cytometry, indicative for bacteria with disrupted membrane. Both triclosan and CBD induced membrane hyperpolarization, although there was no additive effect on this parameter. HR-SEM images of CBD-treated bacteria show the appearance of elongated and swollen bacteria with several irregular septa structures, and upon combined treatment with triclosan, the bacteria took on a swollen ellipse and sometimes oval morphology. Increased biofilm formation was observed at sub-MIC concentrations of each compound alone, while combining the drugs at these sub-MIC concentrations, the biofilm formation was prevented. The inhibition of biofilm formation was confirmed by CV biomass staining, MTT metabolic activity, HR-SEM and live/dead together with exopolysaccharide (EPS) staining visualized by spinning disk confocal microscopy. Importantly, the concentrations required for the anti-bacterial and anti-biofilm activities toward S. mutans were non-toxic to the normal Vero epithelial cells. In conclusion, the data obtained in this study propose a beneficial role of combined triclosan/CBD treatment for potential protection against dental caries.

Prolonged Inhibition of Streptococcus mutans Growth and Biofilm Formation by Sustained Release of Chlorhexidine from Varnish Coated Dental Abutments: An in Vitro Study.

Background It has been confirmed that bacterial biofilm covering dental implants is the main microbial source causing preimplant infectious and inflammatory diseases. The purpose of this study was to evaluate the antibacterial/antibiofilm effect of chlorhexidine, incorporated into a sustained-release varnish of chlorhexidine (SRV-CHX) coating, on dental abutments. Materials and Methods Three kinds of dental abutments were used: a high-performance semi-crystalline engineering thermoplastic polyetheretherketone (PEAK) healing abutment, a titanium healing abutment, and a titanium permanent abutment. These abutments were coated with SRV-CHX or SRV-placebo and exposed daily to fresh cultures of Streptococcus mutans. The effect of SRV-CHX on S. mutans growth on agar plates was studied by measuring the zone of inhibition (ZOI) around each tested abutment every day for a period of 36 days. Biofilm formation on the SRV-CHX/placebo-coated abutments was detected using confocal laser scanning microscopy (CLSM) and high-resolution scanning electron microscopy (HR-SEM), energy dispersive X-ray analysis (EDX), and monitored by crystal violet (CV) staining. Results SRV-CHX-coated abutments 2 and 3 were able to inhibit S. mutans growth for 34 days, while abutment 1 inhibited growth for 32 days. Abutment-associated biofilm formation was notably inhibited by SRV-CHX coating after 13 days of incubation with S. mutans. Finally, the biofilm formed around SRV-CHX-coated abutments was completely inhibited up to 12 days of abutment exposure to S. mutans. Conclusion Coating of dental abutments with SRV-CHX demonstrated long-term effective inhibition of S. mutans growth and biofilm formation on the abutment surface.

Potential Combinatory Effect of Cannabidiol and Triclosan Incorporated into Sustained Release Delivery System against Oral Candidiasis.

Candida albicans is a common fungal pathogen. Biofilm formation on various surfaces is an important determinant of C. albicans pathogenicity. Our previous results demonstrated the high potential of cannabidiol (CBD) to affect C. albicans biofilms. Based on these data, we investigated the possibility of incorporating CBD and/or triclosan (an antimicrobial agent that is widely utilized in dentistry) in a sustained-release varnish (SRV) (SRV-CBD, SRV-triclosan) to increase their pharmaceutical potential against C. albicans biofilm, as well as that of the mixture of the agents into SRV (SRV-CBD/triclosan). The study was conducted in a plastic model, on agar, and in an ex vivo tooth model. Our results demonstrated strong antibiofilm activity of SRV-CBD and SRV-triclosan against C. albicans in all tested models. Both formulations were able to inhibit biofilm formation and to remove mature fungal biofilm. In addition, SRV-CBD and SRV-triclosan altered C. albicans morphology. Finally, we observed a dramatic enhancement of antibiofilm activity when combined SRV-CBD/triclosan was applied. In conclusion, we propose that incorporation of CBD or triclosan into SRV is an effective strategy to fight fungal biofilms. Importantly, the data demonstrate that our CBD/triclosan varnish is safe, and is not cytotoxic for normal mammalian cells. Furthermore, we propose that CBD and triclosan being in mixture in SRV exhibit complementary antibiofilm activity, and thus can be explored for further development as a potential treatment against fungal infections.

Sinonasal Stent Coated with Slow-Release Varnish of Chlorhexidine Has Sustained Protection against Bacterial Biofilm Growth in the Sinonasal Cavity: An In Vitro Study.

The aim of the study was to develop a sustained-release varnish (SRV) containing chlorhexidine (CHX) for sinonasal stents (SNS) to reduce bacterial growth and biofilm formation in the sinonasal cavity. Segments of SNS were coated with SRV-CHX or SRV-placebo and exposed daily to bacterial cultures of Staphylococcus aureus subsp. aureus ATCC 25923 or Pseudomonas aeruginosa ATCC HER-1018 (PAO1). Anti-bacterial effects were assessed by disc diffusion assay and planktonic-based activity assay. Biofilm formation on the coated stents was visualized by confocal laser scanning microscopy (CLSM) and high-resolution scanning electron microscopy (HR-SEM). The metabolic activity of the biofilms was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. Disc diffusion assay showed that SRV-CHX-coated SNS segments inhibited bacterial growth of S. aureus subsp. aureus ATCC 25923 for 26 days and P. aeruginosa ATCC HER-1018 for 19 days. CHX was released from coated SNS segments in a pH 6 medium up to 30 days, resulting in growth inhibition of S. aureus subsp. aureus ATCC 25923 for 22 days and P. aeruginosa ATCC HER-1018 for 24 days. The MTT assay showed a reduction of biofilm growth on the coated SNS by 69% for S. aureus subsp. aureus ATCC 25923 and 40% for P. aeruginosa ATCC HER-1018 compared to the placebo stent after repeated exposure to planktonic growing bacteria. CLSM and HR-SEM showed a significant reduction of biofilm formation on the SRV-CHX-coated SNS segments. Coating of SNS with SRV-CHX maintains a sustained delivery of CHX, providing an inhibitory effect on the bacterial growth of S. aureus subsp. aureus ATCC 25923 and P. aeruginosa ATCC HER-1018 for approximately 3 weeks.

Sustained release varnish containing chlorhexidine for prevention of Streptococcus mutans biofilm formation on voice prosthesis surface: an in vitro study.

In this study, we aimed to develop a novel, sustained release varnish (SRV) for voice prostheses (VP) releasing chlorhexidine (CHX), for the prevention of biofilm formation caused by the common oral bacteria Streptococcus mutans on VP surfaces. This study was performed in an in vitro model as a step towards future in vivo trials. VPs were coated with a SRV containing CHX (SRV-CHX) or SRV alone (placebo-SRV) that were daily exposed to S. mutans. The polymeric materials of SRV were composed of ethylcellulose and PEG-400. Biofilm formation was assessed by DNA quantification (qPCR), crystal violet staining, confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and kinetics experiments. The amount of DNA in the biofilms formed by S. mutans on VP surfaces coated once with SRV-CHX (1.024 ± 0.218ng DNA/piece) was 58.5 ± 8.8% lower than that of placebo-SRV-coated VPs (2.465 ± 0.198ng DNA/piece) after a 48-h exposure to S. mutans (p = 0.038). Reduced biofilm mass on SRV-CHX-coated VPs was visually confirmed by CLSM and SEM. CV staining of SRV-CHX single-coated VPs that have been exposed to S. mutans nine times showed a 98.1 ± 0.2% reduction in biofilm mass compared to placebo-SRV-coated VPs (p = 0.003). Kinetic experiments revealed that SRV-CHX triple-coated VPs could delay bacterial growth for 23days. Coating VPs with SRV-CHX has an inhibitory effect on biofilm formation and prevents bacterial growth in their vicinities. This study is a proof-of-principle that paves the way for developing new clinical means for reducing both VPs' bacterial biofilm formation and device failure.

Voice Prosthesis Coated with Sustained Release Varnish Containing Clotrimazole Shows Long-Term Protection against Candida albicans: An InVitro Study.

Fungal biofilm formation on voice prosthesis (VP) is a major health problem that requires repeated replacement of the prosthesis. Candida albicans is one of the pathogens that frequently inhabits the VP. We proposed that coating VPs with sustained-release varnish (SRV) containing clotrimazole (CTZ) might prevent fungal biofilm formation. The long-term antifungal activities of SRV-CTZ- versus SRV-placebo-coated VPs was tested daily by measuring the inhibition zone of C. albicans seeded on agar plates or by measuring the fungal viability of C. albicans in suspension. The extent of biofilm formation on coated VPs was analyzed by confocal microscopy and scanning electron microscopy. We observed that SRV-CTZ-coated VPs formed a significant bacterial inhibition zone around the VPs and prevented the growth of C. albicans in suspension during the entire testing period of 60 days. Fungal biofilms were formed on placebo-coated VPs, while no significant biofilms were observed on SRV-CTZ-coated VPs. HPLC analysis shows that CTZ is continuously released during the whole test period of 60 days at a concentration above the minimal fungistatic concentration. In conclusion, coating VPs with an SRV-CTZ film is a potential effective method for prevention of fungal infections and biofilm formation on VPs.

Optimizing overnight oral appliance for sustained-release varnish delivery system of sirolimus

<h3>Objectives</h3> Intraoral trays can be used to deliver treatment materials and medications for dental or mucosal conditions. Maintaining appropriate salivary levels of the active ingredient is challenging when using local application. We have previously analyzed salivary levels and local effects of slow-release varnishes (with clotrimazole or sirolimus as the active ingredient) during the daytime. The aims of the present study were as follows: (1) to optimize overnight appliances for slow-release medications by measuring saliva and blood levels and (2) to evaluate the safety of overnight use. <h3>Methods</h3> An acrylic tray containing 0.5 mg of sirolimus in a sustained-release varnish was applied to 6 anterior teeth for 12 hours in 10 healthy volunteers. Whole unstimulated saliva was collected 1, 2, 10, and 12 hours after application, and a blood sample was taken after 12 hours. Drug levels were analyzed. Results from slow- and fast-release formulations, varnish application position on the tray (buccal, palatal, or lingual), and tray placement (mandibular vs maxillary) were compared. The volunteers evaluated the varnish and tray. The study was approved the hospital ethics committee. <h3>Results</h3> Salivary sirolimus was undetected with use of the slow formulation. The faster formulation produced salivary concentrations of 0.3-45 ng/mL. The highest salivary levels were observed with a mandibular tray with lingual varnish application (up to 178 ng/mL). The sialometry of all participants was within normal range (0.2-2 mL/min), and the highest drug levels were found when salivary flow was lowest. The medication was undetected in the blood. No local reactions or side effects were reported. <h3>Conclusions</h3> Salivary concentrations of medications delivered using an oral tray can be affected by the release rate of formulation and, more important, by the position of the tray and the varnish within it and salivary flow rate. Overnight oral trays can be used to deliver medications especially when 24-hour drug exposure is desired. Further studies regarding local factors affecting drug release and salivary levels are required.

RETROSPECTIVE EVALUATION OF A NOVEL SUSTAINED-RELEASE IVERMECTIN VARNISH FOR TREATMENT OF WOUND MYIASIS IN ZOO-HOUSED ANIMALS.

Myiasis is a major disease condition in human and veterinary medicine. Domestic, free-ranging, and zoo-housed animals can be severely affected by myiasis. Depending on case severity, multiple treatment episodes may be indicated and can lead to recurrent capturing, handling stress, and anesthetics, all of which increase the risk of adverse responses (including death) individually and also in the herd. As an insecticide, ivermectin is often used for larval control. A total of 28 individual myiasis cases were retrospectively evaluated, out of which 11 cases were also treated using an ivermectin sustained-release varnish (SRV). The clinical outcome of all cases was assessed and the results suggest that the use of a topical ivermectin SRV (with or without concurrent injectable ivermectin) can reduce handling and treatments, has no adverse effects, and has minimal recurrence of the disease when compared with cases treated without it.

Preventive andTherapeutic Effects of Chlorhexidine Containing Varnish on Candida Biofilm

The aim of the study was to assess the preventive and therapeutic efficacy of a sustained-release varnish (SRV) Cervitec Plus� compared with Corsodyl� mouthwash against Candida albicans, Candida parapsilosis, Candida tropicalis and Candida glabrata on acrylate surfaces. Nystatin as the positive control, and sterile saline solution as the negative control, were used. To examine the preventive efficacy of the agents, Candida biofilms were developed in Sabouraud liquid medium, and mature biofilms were treated with the antifungal. To investigate the preventive efficacy, the agents were applied to the wells of the plates and the biofilms were grown in the treated wells. To determine the metabolic activity of biofilms, the XTT-assay was used. In the case of C. albicans and C. parapsilosis, the most effective therapeutic product was Corsodyl� followed by Cervitec Plus� and Nystatin. The differences were statistically significant when Corsodyl� was compared to Nystatin ( p � 0.05). In relation to C. tropicalis and C. glabrata, Corsodyl� showed the greatest therapeutic efficacy followed by Nystatin and Cervitec Plus�. For both species, the results of Corsodyl� and Cervitec Plus� showed statistically significant difference ( p � 0.05). The most effective preventive product for each examined Candida species was Nystatin, followed by Cervitec Plus� and Corsodyl�. Significant differences were between Nystatin and Corsodyl� (p � 0.05). The preventive and therapeutic efficacy of Cervitec Plus� and Corsodyl�, against the examined Candida species, was detected. Because of the disadvantageous side-effects of Nystatin, Cervitec Plus� can be considered as an alternative preventive agent against Candida species.

Chlorhexidine sustained-release varnishes for catheter coating – Dissolution kinetics and antibiofilm properties

Catheter-associated urinary tract infections are difficult to eradicate or prevent, due to their biofilm-related nature. Chlorhexidine, a widely used antiseptic, was previously found to be effective against catheter-related biofilms. For the present study, we developed sustained-release chlorhexidine varnishes for catheter coating and evaluated their antibiofilm properties and chlorhexidine-dissolution kinetics under various conditions. The varnishes were based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit® RL). Chlorhexidine was released by diffusion from a heterogeneous matrix in the case of the ethylcellulose-based formulation, and from a homogeneous matrix in the case of Eudragit® RL. This dictated the release pattern of chlorhexidine under testing conditions: from film specimens, and from coated catheters in a static or flow-through system. Momentary saturation was observed with the flow-through system in Eudragit® RL-based coatings, an effect that might be present in vivo with other formulations as well. The coatings were retained on the catheters for at least 2weeks, and showed prolonged activity in a biological medium, including an antibiofilm effect against Pseudomonas aeruginosa. The current study demonstrates the potential of catheter coatings with sustained release of chlorhexidine in the prevention of catheter-associated urinary tract infections.

Levels of sirolimus in saliva and blood following oral topical sustained-release varnish delivery system application.

Sirolimus (rapamycin) is a mammalian target of rapamycin pathway blocker. The efficacy of sirolimus is currently studied for its antiproliferative properties in various malignancies and particularly in squamous cell carcinoma and other oral disorders. Topical application at the oral cavity can augment sirolimus availability at the site of action by increasing sirolimus levels in saliva and hence efficacy, along with improved safety (low levels in the blood to avoid side effects) and compliance. Our purpose was to evaluate the release profile and safety of a topical sirolimus sustained-release varnish drug delivery system. Sirolimus sustained-release varnish drug delivery system containing a total of 0.5mg of the drug was applied to nine healthy male volunteers. Saliva and blood levels were determined utilizing mass spectrometry and chemiluminescent microparticle immunoassay, respectively. The prolonged release profile and safety were evaluated for the oral topical delivery system. After the application of the drug delivery system, a sustained-release profile was observed in the oral cavity. We have measured moderate sirolimus levels for up to 12h. The safety was confirmed, and systemic sirolimus blood levels were negligible. After an application of sirolimus sustained-release varnish drug delivery system, prolonged drug levels can be achieved in the saliva. The oral topical sirolimus concentrations were potentially therapeutic along with minimal systemic exposure. These results broaden the potential clinical use of sustained-release oral topical rapalogs.

Prevention of Initial Biofilm Formation on Ureteral Stents Using a Sustained Releasing Varnish Containing Chlorhexidine: In Vitro Study

Ureteral stents are being used exceedingly in the field of urology, and with advancements in endourology, this trend is increasing. Bacterial colonization and proliferation on the stent surface may result in urinary tract infections (UTIs) necessitating the administration of antibiotics that, in turn, may lead to the development of antibiotic-resistant bacterial strains. Several studies have shown that sustained release varnish (SRV) combined with antibiotics or antiseptics can prevent the proliferation of bacteria on urethral catheters. This is the first study that evaluates this technique implemented on ureteral stents. We evaluated growth inhibition on ureteral stent segments coated with chlorhexidine (CHX) 1% SRV. The tests were conducted using common urinary pathogens: Enterococci, Pseudomonas, and Escherichia coli. Coated stent segments were inserted into bacterial suspensions. Controls included uncoated stent segments and stents coated with placebo SRV (without CHX). Bacterial growth measured as turbidity and as colony-forming units showed a significant inhibition effect of initial bacteria adhesion to the CHX-SRV coated stent segments compared with the controls (P<0.001). This inhibitory effect was apparent in each of the bacteria tested and was confirmed by inspection of the stent segments under an electron microscope. In a kinetic experiment using CHX 2% SRV, we were able to prolong the growth inhibition effect from 1 week to nearly 2 weeks. We believe this technique may play a significant role in reducing ureteral stent-associated UTIs. Further studies are needed before this approach can be implemented in clinical practice.

Evaluation of Urinary Catheters Coated with Sustained‐Release Varnish of Chlorhexidine in Mitigating Biofilm Formation on Urinary Catheters in Dogs

Biofilm formation occurs commonly on urinary catheters. To assess the efficacy of urinary catheters coated with sustained-release varnish of chlorhexidine in decreasing catheter-associated biofilm formation in dogs. Thirty client-owned dogs. Prospective study. Thirteen dogs were catheterized with urinary catheters coated with sustained-release varnish of chlorhexidine (study group), and 13 dogs were catheterized with an untreated urinary catheter (control group). Presence and intensity of biofilm formation on the urinary catheters were assessed and compared between the groups by evaluating colony-forming units (CFU) of biofilm bacteria, and semiquantitatively, using confocal laser scanning microscopy and electron microscopy. None of the dogs experienced adverse effects associated with the presence of the urinary catheters. Median CFU count of biofilm bacteria at all portions of the urinary catheter was significantly (P < .001) lower in the study compared with the control group. The degree of biofilm formation on the urinary catheters, as evaluated by confocal laser scanning microscopy and electron microscopy, was significantly lower in the study compared with the control group. Electron microscopy examination identified crystals on some of the urinary catheters. The proportion of catheters on which crystals were observed was significantly lower on the distal part of the urinary catheter in the study group compared with the control group (16.7% versus 66.7%, respectively; P = .04). Chlorhexidine sustained-release varnish-coated urinary catheters effectively decrease urinary catheter-associated biofilm formation in dogs.

First Place: Sustained-Release Antibacterial Varnish-Coated Biopsy Needle for Reduction of Infection Rates Following Prostate Biopsy—In VitroModel

During the past decade, the incidence of severe infections after transrectal ultrasonography-guided prostate biopsy has increased. Antibacterial sustained-release varnish has been shown to reduce bacterial infections. This varnish has yet to be tested in the field of urology. We undertook an in vitro study to assess the possibility of reducing infection rates after prostate biopsy by coating the needle with a novel sustained, yet rapid release chlorhexidine varnish (SRV-CHX) specifically modified for prostate biopsy. A model simulating the microbiologic environment of a prostate biopsy was developed. The model consisted of two layers of agar, of which the first represented the rectum and was preinfected with Escherichia coli. The second layer was sterile and represented tissue interposed between the rectum and prostate. SRV-CHX-coated biopsy needles were inserted 12 times through the two layers, into the third agar layer representing the prostate. Infection transmission was determined by assessing bacterial growth at inoculation sites within the agar plate representing the prostate. Bacterial growth inhibition was measured as an inhibition zone on the contaminated agar. Testing the antibacterial effect of the SRV-CHX-coated needle, we found a substantial reduction of infection transmission as well as sustained inhibition of bacterial growth compared with control needles. Needles coated with SRV-CHX offer a new strategy in infection control after prostate biopsy. A new strategy of SRV-coated prostate biopsy needles supplemented with various antibacterial agents, combined with prophylactic oral antibiotics should result in decreased infection rates after prostate biopsies. Further in vitro studies are needed to formulate the SRV with an optimal antibacterial agent.

Second Prize: Sustained Release Varnish Containing Chlorhexidine for Prevention of Biofilm Formation on Urinary Catheter Surface: In Vitro Study

Biofilms on the surfaces of urinary catheters are among the pivotal factors for recurrent and persistent infections in urology. Many techniques have been investigated and applied for eradication of these biofilms--but with no full success. The aim of this study was to examine the effect of sustained release medicated varnish, releasing chlorhexidine, on the formation of biofilm on the urinary catheter surface in an in-vitro model. A batch model was used to test the antibacterial/antibiofilm effect of the sustained release varnish: Catheter pieces coated with sustained release varnishes were placed in bacterial growth medium that was infected with Pseudomonas aeruginosa for 96 hours. Various concentrations of chlorhexidine impregnated in the varnish were tested. After the incubation period, the catheter pieces were assessed for biofilm formation by measuring the optical density, colony-forming units, and using confocal laser scanning microscopy, and electron scanning microscopy. Biofilm growth measurement (colony-forming units [CFU]) on the catheter surface coated with the various concentrations of chlorhexidine in sustained released varnish revealed a 94% reduction with 1% chlorhexidine (P<0.0001) and 43% reduction with 0.1% chlorhexidine (P=0.08) coated varnish in comparison with a positive control or the placebo varnish in preventing biofilm growth of P. aeruginosa. These biologic assays were confirmed using confocal and electron microscopy. Of the various tested concentrations of sustained release varnishes, the 1% chlorhexidine concentration has demonstrated the superior antibiofilm effect on urinary catheters with P. aeruginosa. Although similar varnishes are used in dentistry, it needs extended research in animals before applying this technology in human trials.

Use of a Sustained Release Chlorhexidine Varnish as Treatment of Oral Necrobacillosis in Macropus spp.

Oral necrobacillosis or lumpy jaw is a common cause of morbidity and mortality affecting captive macropods. This article describes several cases of a new treatment regimen using a sustained release chlorhexidine varnish applied locally to the teeth and the gingivae of two Macropus species, eastern grey kangaroos (Macropus gigantus) from Gan-Garoo Australian Park and a red-necked wallaby (Macropus rufogriseus fruticus) from The Tisch Family Zoological Gardens in Jerusalem. The varnish was applied using a horsehair paint brush as three 1- to 2-mm thick layers. The active ingredient in the varnish was the disinfectant chlorhexidine. Results indicated that use of an intraoral sustained release varnish significantly shortens the treatment time and may prevent recurrence.

A novel sustained-release clotrimazole varnish for local treatment of oral candidiasis

The use of dental varnish for therapeutic purposes has been reported for fluoride or antibacterial drugs. Our objectives were to develop a sustained-release varnish containing an antifungal drug (clotrimazole) for topical application and to evaluate the release rate of the drug in human saliva in comparison with an available commercial troche and their acceptance by healthy volunteers. Following in vitro optimization of the release rate from the varnish, we have embarked on a crossover comparative study assessing the oral sensations and pharmacokinetics of a 10-mg clotrimazole oral troche versus a 10-mg sustained-release clotrimazole varnish in 14 human volunteers over a period of 5 h. Saliva samples were assessed for clotrimazole concentration by high performance liquid chromatography analysis. The volunteers' evaluation of the varnish and troche (taste, other sensory changes, convenience, and oral suitability) were recorded. At all time points, salivary clotrimazole concentrations were higher, and the terminal half-life was significantly prolonged in the varnish group in comparison to the control group. This can be attributed to continuous release of clotrimazole from the varnish formulation. The duration of the drug over the minimal inhibitory concentration, following application of the varnish, was more than threefold longer than following administration of the troche. The developed sustained-release varnish can be applied in patients at a lower frequency than troches, thus, achieving higher patient compliance and efficacy. This novel varnish application can serve as the basis for a new treatment approach to oral candidiasis, a very common chronic opportunistic infection with improved clinical outcome.

Formulation, Development and Characterization of Sustained Release Varnishes Containing Amine and Stannous Fluorides

This study describes properties of potential sustained release varnishes (SRV) containing amine fluoride or amine fluoride with stannous fluoride. The release kinetics, antibacterial properties and antiadhesion properties of two potential varnishes were tested. The varnish of ethylcellulose matrix was found to release fluoride for 4 h in vitro, while the formulation based on hydroxypropylmethylcellulose acetate succinate had a rapid release rate. Hydroxyapatite tablets coated with ethylcellulose-based SRV increased adhesion of Streptococcus mutans, while tablets coated with hydroxypropylmethylcellulose acetate succinate-based SRV decreased bacterial adhesion. Both types of SRV demonstrated a strong antibacterial effect on bacteria in biofilm.