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Keywords = sustained-release varnish

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15 pages, 2300 KB  
Article
Sustained Release Varnish of Chlorhexidine for Prevention of Biofilm Formation on Non-Absorbable Nasal and Ear Sponges
by Sari Risheq, Athira Venugopal, Andres Sancho, Michael Friedman, Irit Gati, Ron Eliashar, Doron Steinberg and Menachem Gross
Pharmaceutics 2026, 18(1), 96; https://doi.org/10.3390/pharmaceutics18010096 - 12 Jan 2026
Viewed by 281
Abstract
Background: Non-absorbable polyvinyl alcohol sponges (Merocel) are widely used in otolaryngology for nasal and ear packing but are prone to bacterial colonization and biofilm formation, which may increase infection risk and drive frequent use of systemic antibiotics. Sustained-release drug delivery systems enable [...] Read more.
Background: Non-absorbable polyvinyl alcohol sponges (Merocel) are widely used in otolaryngology for nasal and ear packing but are prone to bacterial colonization and biofilm formation, which may increase infection risk and drive frequent use of systemic antibiotics. Sustained-release drug delivery systems enable prolonged local antiseptic activity at the site of packing while minimizing systemic exposure. Methods: We developed a sustained-release varnish containing chlorhexidine (SRV-CHX) and coated sterile Merocel sponges. Antibacterial, in vitro, activity against Staphylococcus aureus and Pseudomonas aeruginosa was evaluated using kinetic diffusion assays on agar, optical density (OD600) measurements of planktonic cultures, drop plate, ATP-based viability assays, biofilm analysis by MTT metabolic assay, crystal violet bio-mass staining, high-resolution scanning electron microscopy (HR-SEM), and spinning disk confocal microscopy. Results: SRV-CHX-coated sponges produced sustained zones of inhibition on agar plates for up to 37 days against S. aureus and 39 days against P. aeruginosa, far exceeding the usual 3–5 days of clinical sponge use. Planktonic growth was significantly reduced compared with SRV-placebo, and a bactericidal effect persisted for up to 16 days for S. aureus and 5 days for P. aeruginosa before becoming predominantly bacteriostatic. Biofilm formation was markedly inhibited, with suppression of metabolic activity and biomass for at least 33 days for S. aureus and up to 16 days for P. aeruginosa. HR-SEM and confocal imaging confirmed sparse, discontinuous biofilms and predominance of non-viable bacteria on SRV-CHX-coated sponges compared with dense, viable biofilms on the placebo controls. Conclusions: Coating Merocel sponges with SRV-CHX provides prolonged antibacterial and anti-biofilm activity against clinically relevant pathogens. This strategy may reduce dependence on systemic antibiotics and improve infection control in nasal and ear packing applications in otolaryngology. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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14 pages, 3857 KB  
Article
Coating Doyle Nasal Silicone Splints with a Sustained Release Varnish Containing Antibiotics Provides Long-Term Protection from Staphylococcus aureus: An In Vitro Study
by Ahmad Siag, Ronit Vogt Sionov, Irith Gati, Michael Friedman, Doron Steinberg and Menachem Gross
Pharmaceuticals 2025, 18(11), 1746; https://doi.org/10.3390/ph18111746 - 17 Nov 2025
Viewed by 858
Abstract
Background/Objectives: Doyle nasal silicone splints are commonly used in nasal surgeries to maintain the shape of the nasal passage and prevent scar tissue formation. However, these implants are prone to bacterial colonization, particularly by Staphylococcus aureus, which is associated with severely [...] Read more.
Background/Objectives: Doyle nasal silicone splints are commonly used in nasal surgeries to maintain the shape of the nasal passage and prevent scar tissue formation. However, these implants are prone to bacterial colonization, particularly by Staphylococcus aureus, which is associated with severely recurrent and recalcitrant cases of infected sinonasal cavities. The aim of this study was to develop a sustained-release varnish (SRV) with antibacterial properties that can be applied to Doyle splints to provide an antibacterial environment for an extended period. Methods: Doyle nasal splints (1 cm × 1 cm segments) were coated with SRV containing one of the three antibiotics: augmentin, ciprofloxacin, or chloramphenicol. A placebo varnish without antibiotics served as a control. The coated splints were exposed daily to a fresh culture of S. aureus, and antibacterial activity was assessed by monitoring bacterial growth. Antibiofilm activity was determined using an MTT metabolic assay. Antibacterial activity was further studied by the kinetic disk diffusion assay, where the stents were transferred daily to new, freshly coated S. aureus plates. Biofilm formation on the coated splints was visualized by high-resolution scanning electron microscopy (HR-SEM). Results: Doyle segments coated with augmentin, ciprofloxacin, or chloramphenicol effectively inhibited S. aureus planktonic growth for 9 ± 1, 18 ± 1, and 21 ± 1 days, respectively. Biofilm formation was prevented for 10 ± 1, 18 ± 1, and 21 ± 1 days, and bacterial clearance occurred for 14 ± 1, 52 ± 1, and >65 days, respectively. HR-SEM images showed the prevention of biofilm formation on the coated segments. Conclusions: Our findings demonstrate that coating Doyle nasal silicon splints with SRV containing augmentin, ciprofloxacin, or chloramphenicol provides long-term antibacterial and antibiofilm activity, with SRV–chloramphenicol being superior. Further studies are needed to confirm the in vivo efficacy of this approach. Full article
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12 pages, 1836 KB  
Article
Ciprofloxacin-Coated Tympanostomy Tubes with Sustained-Release Varnish: A Novel Strategy to Combat Biofilm Formation by Pseudomonas aeruginosa
by Sari Risheq, Andres Sancho, Michael Friedman, Irith Gati, Ron Eliashar, Doron Steinberg and Menachem Gross
Microorganisms 2025, 13(9), 2039; https://doi.org/10.3390/microorganisms13092039 - 31 Aug 2025
Cited by 1 | Viewed by 1223
Abstract
Objective: The aim of this study is to develop and evaluate the antibacterial and anti-biofilm efficacy of ciprofloxacin-coated tympanostomy tubes (TTs) using a sustained-release varnish (SRV-CIPRO) and introduce a novel tympanic membrane model for preclinical evaluation. Study Design: This was an in vitro [...] Read more.
Objective: The aim of this study is to develop and evaluate the antibacterial and anti-biofilm efficacy of ciprofloxacin-coated tympanostomy tubes (TTs) using a sustained-release varnish (SRV-CIPRO) and introduce a novel tympanic membrane model for preclinical evaluation. Study Design: This was an in vitro experimental study. Setting: This study was conducted in a biofilm research laboratory in an academic medical center. Methods: Sterile fluoroplastic TTs were coated with SRV-CIPRO or placebo varnish. A novel tympanic membrane (TM) model was developed using a layered agar–plastic system. Antibacterial activity, biofilm inhibition, and bacterial viability were assessed through agar diffusion, MTT, ATP quantification, HR-SEM, and SD-CLSM. Results: SRV-CIPRO-coated TTs exhibited sustained antibacterial activity for up to 10 days. Compared to the placebo, SRV-CIPRO significantly inhibited biofilm formation, reduced metabolic activity, and decreased bacterial viability (p < 0.05). Imaging confirmed fewer bacterial colonies on SRV-CIPRO TTs. The TM model allowed realistic testing of tube insertion and infection simulation. Conclusion: SRV-CIPRO-coated TTs offer sustained antibiotic delivery, potentially reducing postoperative otorrhea and biofilm-related complications. The TM model provides a platform for preclinical evaluation of middle ear devices. Full article
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24 pages, 5364 KB  
Article
Polyglactin 910 Meshes Coated with Sustained-Release Cannabigerol Varnish Inhibit Staphylococcus aureus Biofilm Formation and Macrophage Cytokine Secretion: An In Vitro Study
by Mustafa Abudalu, Muna Aqawi, Ronit Vogt Sionov, Michael Friedman, Irith Gati, Yaron Munz, Gil Ohana and Doron Steinberg
Pharmaceuticals 2023, 16(5), 745; https://doi.org/10.3390/ph16050745 - 13 May 2023
Cited by 4 | Viewed by 3015
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
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17 pages, 2740 KB  
Article
Sinonasal Stent Coated with Sustained-Release Varnish of Mometasone Furoate Inhibits Pro-Inflammatory Cytokine Release from Macrophages: An In Vitro Study
by Alessandra Cataldo Russomando, Doron Steinberg, Irith Gati, Ronit Vogt Sionov, Ron Eliashar, Michael Friedman and Menachem Gross
Pharmaceutics 2023, 15(3), 1015; https://doi.org/10.3390/pharmaceutics15031015 - 22 Mar 2023
Cited by 3 | Viewed by 2337
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances and Challenges in Nasal Formulation Developments)
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21 pages, 8487 KB  
Article
Improved Anti-Biofilm Effect against the Oral Cariogenic Streptococcus mutans by Combined Triclosan/CBD Treatment
by Maayan Avraham, Doron Steinberg, Tamar Barak, Miriam Shalish, Mark Feldman and Ronit Vogt Sionov
Biomedicines 2023, 11(2), 521; https://doi.org/10.3390/biomedicines11020521 - 10 Feb 2023
Cited by 25 | Viewed by 4066
Abstract
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 [...] Read more.
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. Full article
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15 pages, 2687 KB  
Article
Potential Combinatory Effect of Cannabidiol and Triclosan Incorporated into Sustained Release Delivery System against Oral Candidiasis
by Mark Feldman, Irith Gati, Ronit Vogt Sionov, Sharonit Sahar-Helft, Michael Friedman and Doron Steinberg
Pharmaceutics 2022, 14(8), 1624; https://doi.org/10.3390/pharmaceutics14081624 - 3 Aug 2022
Cited by 11 | Viewed by 3111
Abstract
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 [...] Read more.
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. Full article
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14 pages, 2685 KB  
Article
Sinonasal Stent Coated with Slow-Release Varnish of Chlorhexidine Has Sustained Protection against Bacterial Biofilm Growth in the Sinonasal Cavity: An In Vitro Study
by Alessandra Cataldo Russomando, Ronit Vogt Sionov, Michael Friedman, Irith Gati, Ron Eliashar, Doron Steinberg and Menachem Gross
Pharmaceutics 2021, 13(11), 1783; https://doi.org/10.3390/pharmaceutics13111783 - 25 Oct 2021
Cited by 11 | Viewed by 3088
Abstract
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 [...] Read more.
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. aureussubsp. 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. aureussubsp. 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. aureussubsp. 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. aureussubsp. aureus ATCC 25923 and P. aeruginosa ATCC HER-1018 for approximately 3 weeks. Full article
(This article belongs to the Special Issue Biofilm Busting Strategies for Eradicating Infections)
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14 pages, 5305 KB  
Article
Voice Prosthesis Coated with Sustained Release Varnish Containing Clotrimazole Shows Long-Term Protection against Candida albicans: An In Vitro Study
by Ronit Vogt Sionov, Irith Gati, David Kirmayer, Michael Friedman, Doron Steinberg and Menachem Gross
Molecules 2021, 26(17), 5395; https://doi.org/10.3390/molecules26175395 - 5 Sep 2021
Cited by 6 | Viewed by 2756
Abstract
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) [...] Read more.
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. Full article
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10 pages, 1147 KB  
Article
Fluoride Release from Two High-Viscosity Glass Ionomers after Exposure to Fluoride Slurry and Varnish
by Hani M. Nassar and Jeffrey A. Platt
Materials 2019, 12(22), 3760; https://doi.org/10.3390/ma12223760 - 15 Nov 2019
Cited by 10 | Viewed by 3575
Abstract
The effect of brushing with different fluoride slurries on the fluoride release (FR) of different high-viscosity glass ionomer cements (GICs) was investigated. Fifty-eight discs were fabricated from two high-viscosity GICs (GC Fuji IX (F9) and 3M ESPE Ketac-fil (KF)). Five specimens from each [...] Read more.
The effect of brushing with different fluoride slurries on the fluoride release (FR) of different high-viscosity glass ionomer cements (GICs) was investigated. Fifty-eight discs were fabricated from two high-viscosity GICs (GC Fuji IX (F9) and 3M ESPE Ketac-fil (KF)). Five specimens from each brand were used to measure Vickers microhardness and the remaining were randomly assigned to one of four groups (n = 6) based on two-factor combinations: (1) fluoride concentration in the abrasive slurry (275 or 1250 ppm fluoride as NaF) and (2) immersion in a 22,500 ppm fluoride-containing solution. Specimens were brushed for a total of 20,000 strokes over 4 days with daily FR measurement. Data were analyzed using analysis of variance and Bonferroni tests (α = 0.05). Baseline FR and microhardness values were different between the two tested material brands. Exposure to a 22,500 ppm solution was associated with higher FR but not the exposure to 1250 ppm slurries. Brushing and immersion of glass ionomer cements in a 22,500 ppm F solution led to higher FR that was more sustained for KF. Type of the glass ionomer, progressive brushing, and fluoride varnish affected FR but not the fluoride content in the abrasive slurry. Full article
(This article belongs to the Section Biomaterials)
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14 pages, 989 KB  
Review
Layered Double Hydroxide Fluoride Release in Dental Applications: A Systematic Review
by Agron Hoxha, David G. Gillam, Andy J. Bushby, Amani Agha and Mangala P. Patel
Dent. J. 2019, 7(3), 87; https://doi.org/10.3390/dj7030087 - 2 Sep 2019
Cited by 18 | Viewed by 4672
Abstract
This systematic review appraises studies conducted with layered double hydroxides (LDHs) for fluoride release in dentistry. LDH has been used as antacids, water purification in removing excess fluoride in drinking water and drug delivery. It has great potential for controlled fluoride release in [...] Read more.
This systematic review appraises studies conducted with layered double hydroxides (LDHs) for fluoride release in dentistry. LDH has been used as antacids, water purification in removing excess fluoride in drinking water and drug delivery. It has great potential for controlled fluoride release in dentistry, e.g., varnishes, fissure sealants and muco-adhesive strips, etc. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was followed with two reviewers performing a literature search using four databases: PubMed, Web of Science, Science Direct and Ovid Medline with no date restrictions. Studies including any LDH for ion/drug release in dentistry were included, while assessing the application of LDH and the value of the methodology, e.g., ion release protocol and the LDH production process. Results: A total of 258 articles were identified and four met the inclusion criteria. Based on two in vitro studies and one clinical study, LDH was previously studied in dental materials, such as dental composites and buccal muco-adhesive strips for fluoride release, with the latter studied in a clinical environment. The fourth study analysed LDH powder alone (without being incorporated into dental materials). It demonstrated fluoride release and the uptake of volatile sulphur compounds (VSC), which may reduce halitosis (malodour). Conclusion: LDHs incorporated in dental materials have been previously evaluated for fluoride release and proven to be clinically safe. LDHs have the potential to sustain a controlled release of fluoride (or other cariostatic ions) in the oral environment to prevent caries. However, further analyses of LDH compositions, and clinical research investigating any other cariostatic effects, are required. Full article
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