Triclosan Solution Research Articles

Polymeric nanospheres as strategy to increase the amount of triclosan retained in the skin: passive diffusion vs. iontophoresis

The aim of this study was to evaluate the passive and iontophoretic permeation of triclosan in human skin using a triclosan solution and triclosan-loaded cationic nanospheres in order to determine which of the two strategies is more effective in allowing the deposition of triclosan within the skin. Triclosan-loaded nanospheres were prepared by the emulsification-solvent displacement technique using aminoalkyl methacrylate (Eudragit® RL 100) as polymer matrix. Nanospheres of 261.0 ± 15.1 nm with a positive surface charge (Ψz = 26.0 ± 3.2 mV) were obtained. Drug loading was 62.0 ± 1.7%. Results demonstrated that the amount of triclosan retained within the skin was significantly greater (8.5-fold) when this was encapsulated into cationic nanospheres and administered by passive diffusion than when the triclosan solution was employed. The amount of triclosan retained within the skin when the cationic nanospheres were administered by iontophoresis was 3.1-fold greater than when the triclosan solution was administered by passive diffusion. Iontophoresis proved to be effective in enhancing the passage of triclosan in solution throughout the skin, whereas the triclosan nanospheres could achieve a local effect by forming a controlled release dermal depot.

Formation and enhanced biocidal activity of water-dispersable organic nanoparticles

Water-insoluble organic compounds are often used in aqueous environments in various pharmaceutical and consumer products. To overcome insolubility, the particles are dispersed in a medium during product formation, but large particles that are formed may affect product performance and safety. Many techniques have been used to produce nanodispersions-dispersions with nanometre-scale dimensions-that have properties similar to solutions. However, making nanodispersions requires complex processing, and it is difficult to achieve stability over long periods. Here we report a generic method for producing organic nanoparticles with a combination of modified emulsion-templating and freeze-drying. The dry powder composites formed using this method are highly porous, stable and form nanodispersions upon simple addition of water. Aqueous nanodispersions of Triclosan (a commercial antimicrobial agent) produced with this approach show greater activity than organic/aqueous solutions of Triclosan.

Reduced Susceptibility of Proteus mirabilis to Triclosan

Clinical isolates of Proteus mirabilis causing catheter encrustation and blockage are susceptible to the biocide triclosan (MICs of 0.2 mg/liter). Studies with laboratory models of the bladder have demonstrated that the inflation of catheter retention balloons with triclosan solutions rather than water results in the diffusion of triclosan from the balloons into the surrounding urine and the inhibition of catheter encrustation by P. mirabilis. The aim of this study was to test whether the exposure of P. mirabilis to triclosan under laboratory conditions resulted in the selection of strains with reduced susceptibilities to this biocide. Exposure to triclosan in agar was shown to select mutants with MICs elevated from 0.2 mg/liter up to 80 mg/liter. In a selection of 14 of these strains, the decreased susceptibility was found to be stable and not associated with increased resistance to antibiotics. Experiments with the laboratory models demonstrated that inflation of the catheter balloons with triclosan (10 mg/ml) prevented encrustation and blockage by the parent strain P. mirabilis B2 (MIC, 0.2 mg/liter) and the mutant strain M48 (MIC, 2.0 mg/liter) but had no effect on crystalline biofilm formation by strain M55 (MIC, 40 mg/liter). These results suggest that, in any clinical trial or subsequent clinical use of the strategy, it will be important to monitor the urinary flora of the catheterized patients for P. mirabilis strains with reduced susceptibility to triclosan. The emergence of these strains could undermine the ability of the triclosan strategy to control catheter encrustation.

Some Observations on the Diffusion of Antimicrobial Agents Through the Retention Balloons of Foley Catheters

We examined the ability of antimicrobial agents to diffuse through the retention balloons of urinary catheters and inhibit their encrustation by Proteus mirabilis. An agar diffusion screening test was developed to detect agents capable of diffusing through catheter balloons and inhibiting the growth of P. mirabilis. The effect of inflating the balloons with antibacterials on the ability of P. mirabilis to encrust catheters was tested in laboratory models of the catheterized bladder. Of 18 antimicrobial agents active on P. mirabilis only mandelic acid, phenoxyethanol, nalidixic acid and triclosan diffused through all-silicone catheter balloons to produce zones of inhibition against P. mirabilis. Polyurethane balloons were permeable to gentamicin and fluoroquinolones. Experiments with silicone catheters showed that inflating balloons with mandelic acid (100 gm/l) or ciprofloxacin (10 gm/l) failed to extended the time at which catheters became blocked in models inoculated with P. mirabilis. However, nalidixic acid (50 gm/l) significantly extended the lifespan of catheters (p <0.05). Triclosan (10 gm/l) prevented the increase in urinary pH that induces crystal formation and inhibited the formation of crystalline biofilm, enabling the catheters to drain freely for the full 7-day experimental period. Inflation of silicone catheter retention balloons with solutions of nalidixic acid or triclosan rather than water should be considered as strategies to control catheter encrustation. Polyurethane balloons are more permeable than silicone balloons to gentamicin and the fluoroquinolones, and they should be investigated as an alternative to silicone or latex in catheter manufacture.

Kinetics of triclosan oxidation by aqueous ozone and consequent loss of antibacterial activity: Relevance to municipal wastewater ozonation

Oxidation of the antimicrobial agent triclosan by aqueous ozone ( O 3 ) was investigated to determine associated reaction kinetics, reaction site(s), and consequent changes in antibacterial activity of triclosan. Specific second-order rate constants, k O 3 , were determined for reaction of O 3 with each of triclosan's acid-base species. The value of k O 3 determined for neutral triclosan was 1.3 ( ± 0.1 ) × 10 3 M - 1 s - 1 , while that measured for anionic triclosan was 5.1 ( ± 0.1 ) × 10 8 M - 1 s - 1 . Consequently, triclosan reacts very rapidly with O 3 at circumneutral pH (the pH-dependent, apparent second-order rate constant, k app , O 3 , is 3.8 × 10 7 M - 1 s - 1 at pH 7). The pH-dependence of k app , O 3 and comparison of triclosan reactivity toward O 3 with that of other phenolic compounds indicates that O 3 reacts initially with triclosan at the latter's phenol moiety. k O 3 values for neutral and anionic triclosan were successfully related to phenol ring substituent effects via Brown–Okamoto correlation with other substituted phenols, consistent with electrophilic attack of the triclosan phenol ring. Biological assay of O 3 -treated triclosan solutions indicates that reaction with O 3 yields efficient elimination of triclosan's antibacterial activity. In order to evaluate the applicability of these observations to actual wastewaters, triclosan oxidation was also investigated during ozonation of effluent samples from two conventional wastewater treatment plants. Nearly 100% triclosan depletion was achieved for a 4 mg / L ( 8.3 × 10 - 5 mol / L ) O 3 dose applied to a wastewater containing 7.5 mg / L of DOC, and ∼ 58 % triclosan depletion for dosage of 6 mg / L ( 1.3 × 10 - 4 mol / L ) O 3 to a wastewater containing 12.4 mg / L of DOC. At O 3 doses greater than 1 mg / L ( 2.1 × 10 - 5 mol / L ) , hydroxyl radical reactions accounted for < 35 % of observed triclosan losses in these wastewaters, indicating that triclosan oxidation was due primarily to the direct triclosan– O 3 reaction. Thus, ozonation appears to present an effective means of eliminating triclosan's antibacterial activity during wastewater treatment.

Electro-Fenton degradation of antimicrobials triclosan and triclocarban

The antimicrobials triclosan (2,4,4′-trichloro-2′-hydroxydiphenyl ether) and triclocarban ( N-(4-chlorophenyl)- N′-(3,4-dichlorophenyl)urea) have been degraded by four electro-Fenton systems using undivided electrolytic cells with a Pt or boron-doped diamond (BDD) anode and a carbon felt or O 2 diffusion cathode. The main oxidant is hydroxyl radical ( OH) produced both on the anode surface from water oxidation and in the medium by Fenton's reaction, which takes place between electrogenerated H 2O 2 and Fe 2+ coming from cathodic reduction of O 2 and Fe 3+, respectively. Triclosan from saturated aqueous solutions of pH 3.0 is completely removed in all cells, decreasing its decay rate in the order: Pt/carbon felt > BDD/carbon felt > Pt/O 2 diffusion > BDD/O 2 diffusion, in agreement with their OH generation ability from Fenton's reaction. Glyoxylic, maleic and oxalic acids are identified as aliphatic intermediates. Complexes between oxalic acid and iron ions persist largely in solution, although Fe 2+–oxalato complexes are mineralized by OH in the medium and Fe 3+–oxalato complexes are destroyed by OH on BDD. Analogous treatments of more concentrated triclosan solutions using a 20:80 (v/v) acetonitrile/water mixture as solvent evidence the role of hydroxyl radicals along the degradation. In this hydroorganic medium hydroxylated derivatives such as 2,4-dichlorophenol, 4-chlorocatechol, chlorohydroquinone and chloro- p-benzoquinone, and carboxylic acids such as maleic, oxalic, formic and acetic acids are detected as products. Complete destruction of iron–oxalato complexes and released Cl − ion involves some oxidizing species coming from parallel acetonitrile oxidation. The same electro-Fenton systems also yield the overall removal of triclocarban in acetonitrile/water mixtures, giving rise to urea, hydroquinone, chlorohydroquinone, 1-chloro-4-nitrobenzene and 1,2-dichloro-4-nitrobenzene as primary intermediates.

Phototransformation of triclosan in the presence of TiO2 in aqueous suspension: Mechanistic approach

The photocatalytic degradation of the antimicrobial triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) was studied using different types of TiO2 suspension photocatalysts (Degussa P25, PC50 and PC 500) and excitation wavelength of 365nm. In all cases, the degradation process mainly involved the formation of hydroxyl radicals. Under our experimental conditions and in aerated solutions, the irradiation in the presence of TiO2 P25 permitted the evaluation of the half-lifetime to about 10min. The intermediate byproducts were identified by means of HPLC/MS/MS using electrospray (ES) interfacing technique. They were obtained as a result of three main primary processes: (i) homolytic scission of CO bond leading to the formation of 2,4-dichlorophenol and chlorocatechol, (ii) hydroxylation of the phenolic group and (iii) dechlorination process leading to the formation of 5-chloro-2-(4-chlorophenoxyl)phenol. Under prolonged irradiation efficient mineralisation of triclosan solution was observed as evidenced by means of total organic carbon (TOC) evolution as well as chloride anions formation as a function of irradiation time.

A Strategy for the Control of Catheter Blockage by Crystalline Proteus mirabilis Biofilm Using the Antibacterial Agent Triclosan

Objectives: Catheter blockage by crystalline Proteus mirabilis biofilm is a common complication in patients undergoing long-term indwelling bladder catheterisation. Previously we have shown that inflating the retention balloons of all-silicone catheters with triclosan solutions prevents the encrustation process. The aim of the present work was to examine whether this strategy is effective in latex-based catheters. Methods: Laboratory bladder models were fitted with catheters and the retention balloons inflated with water or various concentrations of triclosan. The urine was inoculated with Pr. mirabilis and the times catheters took to block recorded. Results: Control catheters blocked in mean times ranging from 18 to 27 h. The pH of the urine rose from 6.1 to >8.6. In models with latex-based catheters inflated with 1–10 mg/ml triclosan, the urinary pH was controlled, the numbers of organisms in the urine was reduced and the catheters drained freely for the 7 day experimental period. Electron microscopy confirmed that crystalline biofilm was blocking control catheters. Little sign of encrustation was visible on the test catheters. Conclusion: Inflating the retention balloons with triclosan could have practical applications in controlling encrustation on both latex and silicone-based catheters.

Effectiveness of topical chlorhexidine powder as an alternative to hexachlorophane for the control of Staphylococcus aureus in neonates

We routinely phage-type Staphylococcus aureus isolates from high-risk inpatients each week. This surveillance approach previously identified a five-year outbreak of a methicillin-susceptible S. aureus strain (MSSA, PT 53,85), which affected 202 babies on a regional neonatal unit. We previously reported this outbreak and the multiple staged infection control measures that were required to end it. These included strict emphasis on hand hygiene, environmental and staff surveillance sampling, application of topical triclosan solution and hexachlorophane powder, aseptic handling of a skin protectant material, and use of topical mupirocin for staff nasal carriers of the endemic MSSA strain and for babies colonized or infected with S. aureus. In summer 2000 topical hexachlorophane powder became unavailable and we therefore substituted topical 1% chlorhexidine powder as part of routine umbilical decontamination. We have continued prospective S. aureus surveillance for the past five years to monitor the effect of this practice change. We observed a continued decline in the numbers of monthly MSSA isolates from neonatal unit babies. Since the substitution of chlorhexidine for hexachlorophane, the median monthly number of MRSA isolates has been 0.5 (range 0–4). Only sporadic S. aureus PT 53,85 isolates were recovered. Control of S. aureus in our regional neonatal unit, in particular an endemic MSSA strain, was maintained when topical umbilical hexachlorophane powder was substituted with 1% chlorhexidine powder.

Formation and stabilisation of triclosan colloidal suspensions using supersaturated systems

The aim of this paper is to prepare and stabilise, in situ, colloidal microsuspensions of triclosan using the polymer, hydroxypropyl methylcellulose (HPMC). The suspensions were prepared from supersaturated solutions of triclosan. The cosolvent technique was used to create supersaturation. Propylene glycol and water were used as the cosolvents. The triclosan particles had a large needle-shaped morphology, when grown in the absence of the polymer. Moreover, the particles grew rapidly to sizes greater than 5 μm over a period of 7 h. When HPMC was added, the particle sizes were in the range 90–250 nm depending on the amount of polymer present in the solutions. The stability of the solutions was evaluated over a period of 40 days during which the particle sizes did not vary. The results were consistent with the mechanism proposed by Raghavan et al. [Int. J. Pharm. 212 (2001b) 213].

A comparison of cetylpyridinium chloride, triclosan and chlorhexidine mouthrinse formulations for effects on plaque regrowth

A relatively small number of agents are used in mouthrinse products, although the possible variability in the final formulations is enormous. The aim of this study was to compare equal concentrations of 3 antimicrobial agents, in simple formulations, for plaque inhibition. This 4-day plaque regrowth study was a 5-cell, randomised, double blind cross-over design, involving 20 healthy human volunteers. The mouthrinse formulations were aqueous 0.05% solutions of cetylpyridinium chloride (CPC), chlorhexidine and triclosan, together with a 0.1% CPC and a minus active control rinse. On Day 1, from a zero plaque baseline, volunteers ceased normal oral hygiene and rinsed 2x daily for 1 min. with 10-ml volumes of the allocated rinses. On Day 5, plaque was scored by index and area. All rinses produced lower mean plaque values compared to control, but unlike the CPC and chlorhexidine rinses, the differences with triclosan did not always reach significance. The CPC and chlorhexidine rinses were always significantly more effective than the triclosan rinse. The greatest plaque inhibition was with 0.1% CPC although rarely significantly greater than the 0.05% CPC and chlorhexidine rinses which were similar in efficacy. The results indicate that further studies on lower concentration chlorhexidine solutions are warranted.