Enhanced chlorhexidine skin penetration with 1,8-cineole.

BACKGROUND: Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this study was to compare the depth of CHG skin permeation from solutions containing either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70% (v/v) IPA and 2% (v/v) 1,8-cineole. METHODS: An ex-vivo study using Franz diffusion cells was carried out. Full thickness human skin was mounted onto the cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the skin surface. After twenty-four hours the skin was sectioned horizontally in 100 µm slices to a depth of 2000 µm and the concentration of CHG in each section quantified using high performance liquid chromatography (HPLC). The data were analysed with repeated measures analysis of variance. RESULTS: The concentration of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% - 74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin compared to a CHG solution which did not contain this terpene (P = 0.042). CONCLUSIONS: Enhanced delivery of CHG can be achieved in the presence of 1,8-cineole, which is the major component of eucalyptus oil. This may reduce the numbers of microorganisms located in the deeper layers of the skin which potentially could decrease the risk of surgical site infection.

The Compatibility of Chlorhexidine and a Skin Care Product Line: A Real-World Analysis of Hospital-Acquired Infection Rates.

Chlorhexidine gluconate (CHG) use helps reduce hospital-acquired infections (HAIs). Chlorhexidine gluconate effectiveness can be reduced by use of skin care products. Although laboratory work can be performed to prove compatibility, such work has limitations. The purpose of this study was to compare HAI rates when CHG antiseptic wipes were used in conjunction with a silicone- and micronutrient-based skin care product line (SMSP) and when CHG wipes were used without the SMSP. Using commercial distribution data, 17 hospitals that purchased both CHG wipes and SMSP were identified. Hospital-acquired infection rates from this group were compared with HAI rates from 18 hospitals that used CHG wipes, but not SMSP. Hospital-acquired infection information was obtained from the Leapfrog Group (www.hospitalsafetyscore.org/). Four infection rates were compared: (1) infection in the blood during an intensive care unit stay, (2) infection in the urinary tract during an intensive care unit stay, (3) surgical site infection after colon surgery, and (4) average infection rate from 1 to 3. There was no significant difference between the infection rates of the two groups (Ps ranged from .285 to .983). There was also no statistically significant association between hospital grade and product use (P = .194). When considering publicly available data on HAI, there was no measurable difference in HAI rates between facilities that use CHG wipes with or without an SMSP. The SMSP does not impact the efficacy of CHG wipes.

Antimicrobial Activity of Glass lonomer Cement Incorporated with Chlorhexidine-Loaded Zeolite Nanoparticles.

A functional dental restorative system with antimicrobial properties was developed using zeolite (ZE) nanoparticles (NPs) as a drug delivery carrier. ZE NPs loaded with chlorhexidine (CHX) were prepared using the ionic immobilization method. The resulting CHX-loaded ZE NPs were then incorporated into commercial dental glass ionomer cement (GIC). The average size of the CHX-loaded ZE NPs was about 100 to 200 nm, and the NPs were dispersed homogeneously in the GIC. The in vitro release profile of encapsulated GIC containing CHX showed an early release burst of approximately 30% of the total CHX by day 7, whereas GIC containing CHX-loaded ZE NPs showed a sustained release of CHX without the early release burst in a 4-week immersion study. The agar diffusion test results showed that the GIC incorporated with CHX-loaded ZE NPs showed a larger growth inhibition zone of Streptococcus mutans than GIC alone, indicating that this innovative delivery platform potently imparted antimicrobial activity to the GIC. Moreover, these findings suggest that a range of antimicrobial drugs that inhibit the growth of oral bacteria can be incorporated efficiently into dental GIC using CHX-loaded ZE NPs.

Antibacterial releasing titanium surface using albumin nanoparticle carriers.

We developed a simple and highly efficient method for delivery from titanium (Ti) surfaces using albumin nanoparticle carriers. A Ti disc with a resorbable blasting media surface was used as a metal implant with a localized drug delivery structure. Human serum albumin (HSA) nanoparticles loaded with chlorhexidine (CHX) diacetate salt hydrate as the model drug were fabricated using a desolvation technique. The CHX-loaded HSA nanoparticles produced were cross linked with glutaraldehyde (GA). The nanoparticles were pre-coated with positively-charged polyethylenimine (PEI) molecules and then immobilized via electrical interactions on the negatively charged Ti disc surface. Our results suggested that the PEI-coated HSA nanoparticles loaded with CHX (PEI-CHX-HSA) were incorporated successfully and well-dispersed on the Ti disc surfaces. The agar diffusion test on the Ti surface treated with PEI-CHX-HSA nanoparticles showed a larger growth inhibition zone of Streptococcus mutans versus the control Ti surface, suggesting that this innovative delivery platform imparts potent antibacterial activity to the Ti surface. Thus, CHX, which inhibits the growth of oral bacteria, can be efficiently incorporated onto Ti surfaces by using HSA nanoparticles.

Candidacidal effect of fluconazole and chlorhexidine released from acrylic polymer.

OBJECTIVES: To investigate the efficacy and rate of killing of a fluconazole- or chlorhexidine-impregnated polymeric delivery system against fluconazole-susceptible and -resistant Candida albicans and fluconazole-resistant Candida glabrata. METHODS: Poly(ethyl methacrylate)/tetrahydrofurfuryl methacrylate (PEM/THFM) discs impregnated with chlorhexidine, pure fluconazole (FLCp) or fluconazole from capsules (FLCc) were prepared by substituting a portion of PEM powder with an equivalent amount of each drug. Discs were incubated in sterile water for 1, 3, 7, 14, 21 and 28 days. The amounts of drugs in the leachates were measured spectrophotometrically and their antifungal activity against fluconazole-susceptible (n=1) and fluconazole-resistant (n=2) candidal isolates was determined using a time-kill method and by comparing the released concentrations with the corresponding MICs. RESULTS: Fluconazole and chlorhexidine leached from PEM/THFM polymer for up to 28 days and the released concentrations were fungicidal against all three Candida isolates for at least the first 7 days. Chlorhexidine leachates killed all Candida isolates more rapidly than the two fluconazole formulation leachates throughout the study period. FLCc leachates required longer incubation for 100% killing than FLCp leachates. The proportion of viable C. glabrata dropped more slowly than that of C. albicans with the same MIC. CONCLUSIONS: The concentrations of chlorhexidine and fluconazole leached from the PEM/THFM polymer were fungicidal against all Candida isolates, including those resistant to fluconazole, for the first 7 days. Chlorhexidine leachates showed a rapid fungicidal activity for up to 4 weeks, which can be of use in cases with poor response to conventional antifungals.

Distribution and visualisation of chlorhexidine within the skin using ToF-SIMS: a potential platform for the design of more efficacious skin antiseptic formulations.

PURPOSE: In order to increase the efficacy of a topically applied antimicrobial compound the permeation profile, localisation and mechanism of action within the skin must first be investigated. METHODS: Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to visualise the distribution of a conventional antimicrobial compound, chlorhexidine digluconate, within porcine skin without the need for laborious preparation, radio-labels or fluorescent tags. RESULTS: High mass resolution and high spatial resolution mass spectra and chemical images were achieved when analysing chlorhexidine digluconate treated cryo-sectioned porcine skin sections by ToF-SIMS. The distribution of chlorhexidine digluconate was mapped throughout the skin sections and our studies indicate that the compound appears to be localised within the stratum corneum. In parallel, tape strips taken from chlorhexidine digluconate treated porcine skin were analysed by ToF-SIMS to support the distribution profile obtained from the skin sections. CONCLUSIONS: ToF-SIMS can act as a powerful complementary technique to map the distribution of topically applied compounds within the skin.

Antimicrobial activity of a chlorhexidine intravascular catheter site gel dressing.

OBJECTIVES: The antimicrobial efficacy of a chlorhexidine gluconate (CHG) intravascular catheter gel dressing was evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and an extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli. Chlorhexidine deposition on the skin surface and release from the gel were determined. METHODS: The antimicrobial efficacy was evaluated in in vitro studies following microbial inoculation of the dressing and application of the dressing on the inoculated surface of a silicone membrane and donor skin [with and without a catheter segment and/or 10% (v/v) serum] on diffusion cells. Antimicrobial activity was evaluated for up to 7 days. Chlorhexidine skin surface deposition and release were also determined. RESULTS: MRSA and E. coli were not detectable within 5 min following direct inoculation onto the CHG gel dressing. On the silicone membrane, 3 log and 6 log inocula of MRSA were eradicated within 5 min and 1 h, respectively. Time to kill was prolonged in the presence of serum and a catheter segment. Following inoculation of donor skin with 6 log cfu of MRSA, none was detected after 24 h. Chlorhexidine was released from the gel after a lag time of 30 min and increasing amounts were detected on the donor skin surface over the 48 h test period. The CHG gel dressing retained its antimicrobial activity on the artificial skin for 7 days. CONCLUSIONS: The CHG intravascular catheter site gel dressing had detectable antimicrobial activity for up to 7 days, which should suppress bacterial growth on the skin at the catheter insertion site, thereby reducing the risk of infection.

Reactive calcium-phosphate-containing poly(ester-co-ether) methacrylate bone adhesives: setting, degradation and drug release considerations.

This study has investigated novel bone adhesives consisting of fluid photo-polymerizable poly(lactide-co-propylene glycol-co-lactide)dimethacrylate (PGLA-DMA) mixed with systematically varying fillers of ß-tricalcium phosphate (ß-TCP) and monocalcium phosphate monohydrate (MCPM), for the delivery of an antibacterial drug chlorhexidine (CHX). All formulations were found to polymerize fully within 200 s after exposure to blue light. In addition, water sorption by the polymerized materials catalyzed varying filler conversion to dicalcium phosphate (DCP) (i.e. brushite and monetite). With greater DCP levels, faster degradation was observed. Moreover, increase in total filler content enhanced CHX release, associated with higher antibacterial activity. These findings thus suggest that such rapid-setting and degradable adhesives with controllable drug delivery property could have potential clinical value as bone adhesives with antibacterial activity.

Aqueous Chlorhexidine Compared with Povidone-Iodine as Ocular Antisepsis before Intravitreal Injection: A Randomized Clinical Trial.

PURPOSE: Topical povidone-iodine (PI) is widely used as an ocular surface antiseptic for intravitreal injections (IVIs). Although PI is generally well tolerated, it can be associated with significant ocular irritation. Aqueous chlorhexidine (AqCHX) has been described as a possibly better tolerated antimicrobial for ophthalmic procedures. We compared patient pain scores, ocular surface characteristics, and antimicrobial efficacy between PI 5% and AqCHX 0.1% during IVIs. DESIGN: Prospective single-center, randomized clinical trial. PARTICIPANTS: Patients receiving same-day bilateral intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Each patient had 1 eye randomized to PI or AqCHX, and the second eye received the other agent. Both eyes received topical proparacaine 0.5%. MAIN OUTCOME MEASURES: After IVIs, participants rated their pain (Wong-Baker, scale 0-10) for each eye 1 minute after PI or AqCHX instillation and 1 day after the procedure. Each eye was assessed using a standardized quantitative grading system of corneal epitheliopathy (ocular staining score). Microbial swab cultures of the conjunctiva both before instillation of topical antisepsis and 10 minutes after IVIs were given. RESULTS: A total of 100 eyes of 50 patients were included. The mean patient age was 68 years (range, 39-92), and 30 of 50 (60%) were male. Compared with AqCHX, eyes receiving PI had a greater mean pain score immediately after injection (1.44 vs. 0.44, P < 0.001) but not on postprocedure day 1 (1.04 vs. 0.48, P = 0.06). Eyes that received PI had a higher ocular staining score indicating worse corneal epitheliopathy (4.22 vs. 3.10, P < 0.001). There was no difference in rates of positive microbial cultures between groups. There was no difference in rates of adverse events between groups (P = 0.99), and no cases of endophthalmitis occurred. CONCLUSIONS: Povidone-iodine demonstrated greater ocular surface discomfort and corneal epitheliopathy compared with AqCHX during same-day bilateral IVIs. The 2 agents otherwise demonstrated no difference in positive microbial cultures or adverse events. Aqueous chlorhexidine may be a better tolerated alternative to PI for antimicrobial prophylaxis during IVIs for some patients.

Dendrimer-mediated permeation enhancement of chlorhexidine digluconate: Determination of in vitro skin permeability and visualisation of dermal distribution.

Chlorhexidine digluconate (CHG) is a cationic bisbiguanide used in the UK as the first-line skin antiseptic prior to surgery in the UK due to its favourable efficacy and safety profile, high affinity for skin binding and minimal reports of resistance. Despite this, bacteria remain within deeper skin layers, furrows and appendages that are considered inaccessible to CHG, due to its poor dermal penetration. In this study a third generation, polyamidoamine dendrimer (G3 PAMAM-NH2) was utilised to improve dermal penetration of CHG. A topical gel formulation was optimised to maximise CHG delivery (containing 0.5% gelling agent and 4% drug), followed by drug and dendrimer co-formulation into a commercially viable gel. The gel containing 4% CHG and 1 mM PAMAM dendrimer significantly increased the depth permeation of CHG compared to the commercial benchmark (Hibiscrub®, containing 4% w/v CHG) (p < 0.05). The optimised formulation was further characterised using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), which indicated that the depth of dermal penetration achieved was sufficient to reach the skin strata that typically harbours pathogenic bacteria, which is currently inaccessible by commercial CHG formulations. This study therefore indicates that a G3 PAMAM-NH2 dendrimer gel may be viable as a permeation enhancer of CHG, for improved skin antisepsis in those at risk of a skin or soft tissue infection as a result of surgical intervention.

Enhanced chlorhexidine skin penetration with eucalyptus oil.

BACKGROUND: Chlorhexidine digluconate (CHG) is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG) when used as a skin antiseptic. METHOD: Chlorhexidine was applied to the surface of donor skin and its penetration and retention under different conditions was evaluated. Skin penetration studies were performed on full-thickness donor human skin using a Franz diffusion cell system. Skin was exposed to 2% (w/v) CHG in various concentrations of eucalyptus oil (EO) and 70% (v/v) isopropyl alcohol (IPA). The concentration of CHG (µg/mg of skin) was determined to a skin depth of 1500 µm by high performance liquid chromatography (HPLC). RESULTS: The 2% (w/v) CHG penetration into the lower layers of skin was significantly enhanced in the presence of EO. Ten percent (v/v) EO in combination with 2% (w/v) CHG in 70% (v/v) IPA significantly increased the amount of CHG which penetrated into the skin within 2 min. CONCLUSION: The delivery of CHG into the epidermis and dermis can be enhanced by combination with EO, which in turn may improve biocide contact with additional microorganisms present in the skin, thereby enhancing antisepsis.

A novel injectable chlorhexidine thermosensitive hydrogel for periodontal application: preparation, antibacterial activity and toxicity evaluation.

The aim of this paper was to evaluate the application potential of CS-HTCC/GP-0.1%Chx thermosensitive hydrogel which was synthesized using chitosan (CS), quaternized CS, and alpha,beta-glycerophosphate (alpha,beta-GP) loading with 0.1% chlorhexidine (Chx) (w/v) for periodontal treatment. An aqueous solution of CS-HTCC/GP-0.1%Chx was transformed into hydrogel at 6 min when the temperature was increased to 37 degrees C. The scan electron microscopy (SEM) image of the gel was a porous, loose and crosslinked network. In vitro, Chx released over 18 h from the CS-HTCC/GP thermosensitive hydrogel in artificial saliva pH 6.8. Release rate could be controlled through adjustment of alpha,beta-GP or Chx concentration. CS-HTCC/GP-0.1%Chx thermosensitive hydrogel exhibited excellent inhibitory activity against primary periodontal pathogens. CS-HTCC/GP-0.1%Chx thermosensitive hydrogel had no acute toxicity; the maximum tolerated dose in rats was 400 mg/ml. All results indicated that CS-HTCC/GP-0.1%Chx thermosensitive hydrogel is a strong candidate as a local drug delivery system for periodontal treatment.

Determination of chlorhexidine retention in different oral sites using matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

OBJECTIVE: The aim of this study was to determine chlorhexidine retention in different oral sites after a one-time 30 s mouth rinsing. DESIGN: Five volunteers were asked to rinse their mouth with 10 ml of 0.2 % chlorhexidine digluconate for 30 s. After rinsing, samples were collected from the interdental area, buccal dental pellicle, anterior labial and posterior buccal mucosa, and saliva with a microbrush at five-time points within 24 h. Retention of chlorhexidine was measured using matrix-assisted laser desorption/ionization-time of flight mass spectrometry with a quantification limit of 15 ng/ml. RESULTS: Chlorhexidine remained in the oral cavity at micrograms per milliliter levels for 11 h after mouth rinsing and was even detected 24 h after application. The results showed a distinct decline of intraoral chlorhexidine levels during the first 6 h after rinsing and it was then retained at low concentrations for at least 24 h. CONCLUSIONS: The dental pellicle and oral mucosa were favorable sites for chlorhexidine retention. The novel method used for chlorhexidine determination offered excellent quantification limits and readily permitted quantification of chlorhexidine.

Mucoadhesive thin films for the simultaneous delivery of microbicide and anti-inflammatory drugs in the treatment of periodontal diseases.

There is an unmet clinical need for new products to address the high percentage of the populous who present with periodontal diseases. Drug dose retention at the point of application would facilitate sustained release and more efficacious treatments. The aim of this study was to evaluate mucoadhesive polymeric thin films for simultaneous in situ delivery chlorhexidine and anti-inflammatory and analgesic drugs. Mucoadhesive thin films were prepared using a polymer mixture containing chlorhexidine (25 mg) ± diclofenac sodium (10 and 50 mg), and lidocaine hydrochloride (10 mg) or betamethasone dipropionate (10 and 50 mg). The films were assessed for in vitro drug release and localised tissue delivery, followed by determination of modulated prostaglandin E2 (PGE2) levels in ex vivo tissue and cytotoxicity using a HaCaT keratinocyte cell line. Antibacterial activity of the chlorhexidine/diclofenac film was determined against planktonic and biofilm bacteria associated with periodontal disease and dental plaque. Chlorhexidine release was consistently low (up to 10% of initial loading) from all films, whereas the release of diclofenac, betamethasone and lidocaine exceeded 50% within 30 min. The 50 mg betamethasone film released up to 4-fold more than the 10 mg film. Statistically significant reduction of PGE2 was observed in ex vivo porcine gingival tissue for films containing chlorhexidine with or without diclofenac, and betamethasone. No cytotoxicity was observed for any film, apart from 50 mg betamethasone at 24 h. Films loaded with chlorhexidine and diclofenac were inhibitory against relevant test bacteria. Between 3 and 6 log10 reductions in bacterial cell recovery was observed after biofilm exposure to the chlorhexidine films irrespective of the presence of the anti-inflammatory or anaesthetic. This work demonstrated that thin film formulations have the potential to simultaneously counter key causative factors in periodontal diseases, namely associated bacteria biofilm and chronic local inflammation.

High-performance liquid chromatographic determination of chlorhexidine in whole blood by solid-phase extraction and kinetics following an intravenous infusion in rats.

This paper presents the extraction and analysis of chlorhexidine (CHX) from whole blood using solid-phase extraction (SPE) together with high-performance liquid chromatography (HPLC). Blood samples, spiked with chlorpromazine used as an internal standard, were fortified with sodium acetate buffer and purified with Bakerbond C(18) SPE columns. The columns were washed, dried, and eluted with experimental optimized solvent systems. The HPLC was performed using a Capcell Pak C(18) MG column (4.6 x 250-mm) and monitored at 260 nm, using a UV detector. A mobile phase consisting of acetonitrile/water (40:60 v/v), containing 0.05% trifluoroacetic acid, 0.05% heptafluorobutyric acid, and 0.1% triethylamine, was employed. The assay was linear over the range of 0.05 to 2.0 microg/g and the limit of detection was 0.01 microg/g for CHX in whole blood. At the concentration range of 0.05 to 2.0 microg/g, the recoveries ranged from 72% to 85%, and the intra- and interday precision, expressed as coefficient of variation, were less than 11% and 13%, respectively. Kinetic characteristics following an intravenous infusion of a CHX product, Maskin solution, at a dose of 15 mg/kg in rats were evaluated using the present method. The kinetic profiles of CHX conformed to a two-compartment model with an alpha half-life (of distribution) at 0.05 h and a beta half-life (of elimination) at 0.55 h in rats. The method is simple and reliable for the determination of CHX in blood samples and could be expected to apply to forensic and clinical specimens.

Dissolution Chamber for Small Drug Delivery System in the Periodontal Pocket.

Existing dissolution chambers have relatively large volume compared to the size of the periodontal pocket. A small volume dissolution method that simulates the physiological release environment for periodontal drug delivery is needed. The objectives were to construct a small, more physiologically relevant, dissolution chamber and investigate the properties of the new dissolution chamber for the assessment of sustained drug release systems in periodontal delivery. Flow-through dissolution chambers were constructed using three-dimensional (3D) printing. Drug release experiments were performed using the dissolution chamber and a commercially available long-acting periodontal insert product, PerioChip®. Similar experiments were performed under more traditional larger volume bulk solution conditions for comparison. Computer simulations and experimental results showed that drug clearance from the dissolution chamber was fast compared to drug release from the periodontal product. Drug clearance from the flow-through dissolution chamber and drug release from the sustained release product in the chamber were related to the dissolution medium flow rate and chamber volume. Drug release in the flow-through chamber was slower than that observed in bulk solution, but approached it when the medium flow rate increased. The presence of trypsin in the dissolution medium enhanced drug release from the product. A flow-through dissolution system was constructed that could evaluate drug release from a sustained release product in a small dimension environment by modifying the flow rate and composition of the dissolution medium.

Physicochemical and biological properties of novel chlorhexidine-loaded nanotube-modified dentin adhesive.

A commercially available three-step (etch-and-rinse) adhesive was modified by adding chlorhexidine (CHX)-loaded nanotubes (Halloysite®, HNT) at two concentrations (CHX10% and CHX20%). The experimental groups were: SBMP (unmodified adhesive, control), HNT (SBMP modified with HNT), CHX10 (SBMP modified with HNT loaded with CHX10%), and CHX20 (SBMP modified with HNT loaded with CHX20%). Changes in the degree of conversion (DC%), Knoop hardness (KHN), water sorption (WS), solubility (SL), antimicrobial activity, cytotoxicity, and anti-matrix metalloproteinase [MMP-1] activity (collagenase-I) were evaluated. In regards to DC%, two-way ANOVA followed by Tukey's post-hoc test revealed that only the factor "adhesive" was statistically significant (p < 0.05). No significant differences were detected in DC% when 20 s light-curing was used (p > 0.05). For Knoop microhardness, one-way ANOVA followed by the Tukey's test showed statistically significant differences when comparing HNT (20.82 ± 1.65) and CHX20% (21.71 ± 2.83) with the SBMP and CHX10% groups. All adhesives presented similar WS and cytocompatibility. The CHX-loaded nanotube-modified adhesive released enough CHX to inhibit the growth of S. mutans and L. casei. Adhesive eluates were not able to effectively inhibit MMP-1 activity. The evaluation of higher CHX concentrations might be necessary to provide an effective and predictable MMP inhibition. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 868-875, 2019.

Cost-effectiveness analysis and safety of erythromycin 4% gel and 4% chlorhexidine scrub for pitted keratolysis treatment.

Background: Studies of Pitted keratolysis (PK) treatment are limited. Objectives: To study cost-effectiveness and to compare the safety of 4% chlorhexidine scrub with 4% erythromycin gel, for PK infections. Materials and methods: This cohort study was conducted on naval rating cadets with a clinical diagnosis of PK at Chumpol Naval Rating School, Thailand in 2016. Participants were randomly treated with either 4% erythromycin gel or 4% chlorhexidine scrub for 4 weeks. The clinical examinations were evaluated at the baseline and at 1 and 2 months after treatment. A decision-tree model was used to evaluate the costs, resource utilization and outcomes as quality-adjusted life-years (QALYs). Results: Of 344 naval rating cadets, 125 (36.3%) were diagnosed with PK. Sixty-four were treated with erythromycin. Approximately 80% of participants had complete resolution Foot odor were significantly improved at 2 months (p < .001) for both groups. No adverse effects were reported. Total cost for 4 weeks' treatment with the erythromycin gel and chlorhexidine scrub was US$77.34, US$51.9, respectively. Chlorhexidine treatment and erythromycin gel had 0.1526 and 0.1425 QALYs, respectively. Conclusions: treatment of PK with either 4% chlorhexidine scrub or 4% erythromycin gel had similar outcomes. However, using chlorhexidine scrub was more cost-effective.

Addition of phosphates and chlorhexidine to resin-modified MTA materials.

To evaluate the properties of experimental mineral trioxide aggregate (MTA) resin-modified materials for root-end filling procedures, varying their compositions regarding the addition of hydroxiapatite (HA) or dicalcium phosphate dihydrate, with or without chlorhexidine digluconate. White MTA (Angelus, Londrina, Brazil) was used as a reference material. Degree of conversion (DC) was evaluated by Fourier transformed infrared (FTIr) spectroscopy (n = 5). Flowability (n = 3) and radiopacity (n = 3) were evaluated following ISO 6876:2001 methods. For splitting tensile strength analysis, cylindrical samples (n = 10) were subjected to compressive load using a universal testing machine (Instron Corporation, Norwood, MA). Water sorption and solubility tests were performed according to ISO 4049:2009 methods. Calcium ion release and pH analysis (n = 10) were evaluated using a pH meter (Orion, Watsonville, CA). Cytotoxicity (n = 8) of materials extracts was evaluated as cell viability percentage. Statistical analysis was performed using Kolmogorov-Smirnov for normal distribution and data was subjected to one-way ANOVA and Tukey test (α = 0.05). Addition of chlorhexidine digluconate reduced DC mean values for experimental materials (<50%). White MTA demonstrated lower flowability (5.3 mm) and higher radiopacity (9.8 mm Al), splitting tensile strength (9.1 MPa), solubility (8.2 µg/mm3 ), calcium ion release (~26.5 ppm), cytotoxicity (55.2%), and pH mean values (10.8), when compared to experimental materials. All groups demonstrated a decrease in calcium release (<85%) and pH (<13%). Formulation containing HA demonstrated similar pH values after 28 days when compared to white MTA. Evaluated experimental resin-modified MTA based materials without chlorhexidine digluconate showed satisfactory results for all physico-chemical properties tested and cytotoxicity. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2195-2201, 2019.

Dual 0.02% chlorhexidine digluconate - 0.1% disodium EDTA loaded thermosensitive ocular gel for Acanthamoeba keratitis treatment.

Poor bioavailability and low residence time limit the efficiency of conventional biguanide-based eye drops against Acanthamoeba keratitis. The aim of this work was to formulate an original anti-amoebic thermoreversible ocular gel combining biguanide and metalloproteases inhibitor - chelating agent. Chlorhexidine digluconate (CHX)-ethylenediaminetetraacetic acid disodium salt (Na2EDTA) were compounded in poloxamer 407 saline solution. 0.02% CHX - 0.1% Na2EDTA loaded thermosensitive ocular gel exhibited appropriate pH (5.73 ±â€¯0.06), iso-osmolality (314 ±â€¯5 mOsm/kg), viscosity (ranged between 15 and 25 mPa.s) and thermal gelation (26.5 °C and 33 °C) properties. Bioadhesion of gel was successfully tested onto isolated bovine eyes as well as the assessment of CHX penetration into the cornea. Intracorneal CHX concentration was found greater than trophozoite minimum amoebicidal concentration and minimal cysticidal concentration after 15-min and 2-h ocular exposure, respectively, while any CHX permeation through the cornea was detected (<51 ng/cm2/h). Improvement of CHX ocular bioavailability was attributed to probable solubilization of tear film lipid layer by poloxamer. In vitro efficiency of CHX-Na2EDTA ocular gel was confirmed from the drastic reduction of trophozoite and cyst survival (to 25% and 2%, respectively), confirming the potential of the multicomponent pharmaceutical material strategy for the treatment of Acanthamoeba keratitis.