Search

Purpose: To investigate the influence of benzalkonium chloride (BAK) on ocular surface disease (OSD) in glaucoma patients receiving ocular-hypotensive agent. Methods: Patients were randomized to re...

BACKGROUND Biocides are frequently used as preservative, disinfectant and sterilizer against many microorganisms in hospitals, industry and home. However, the reduced susceptibility rate of Pseudomonas aeruginosa (P. aeruginosa) strains to biocides is increasing. The aim of this study was to evaluate the antimicrobial activity of four frequently used biocides against P. aeruginosa and to determine the prevalence of genes involved in biocide resistance. METHODS A total of 76 clinical isolates of P. aeruginosa strains were used in the present study. The minimum inhibitory concentrations (MICs) of four biocides, i.e. chlorhexidine digluconate, benzalkonium chloride, triclosan and formaldehyde, against P. aeruginosa strains were determined using agar dilution method. In addition, the prevalence of biocide resistance genes was determined using the polymerase chain reaction (PCR) method. RESULTS In the present study, the highest MIC90 and MIC95 (epidemiological cut-off) values were observed for benzalkonium chloride (1024 μg/mL), followed by formaldehyde (512 μg/mL), triclosan (512 μg/mL) and chlorhexidine digluconate (64 μg/mL). Furthermore, the prevalence of qacEΔ1, qacE, qacG, fabV, cepA and fabI genes were 73.7% (n = 56), 26.3% (n = 20), 11.8% (n = 9), 84.2% (n = 64), 81.5% (n = 62) and 0% (n = 0), respectively. A significant association was observed between the presence of biocide resistance genes and MICs (p 0.05), except for levofloxacin and norfloxacin antibiotics and qacE and qacG genes (p

Lasting disinfection effects, that is, the residual disinfection effects (RDEs), of skin-coated disinfectants have rarely been considered for infection control owing to the challenges involved in the accurate evaluation of RDEs. In this study, we constructed a new skin evaluation model and determined the RDEs of existing disinfectants against viruses. Our results showed that ethanol and isopropanol had no RDE, whereas povidone-iodine, chlorhexidine gluconate, and benzalkonium chloride (BAC) exhibited RDEs, with 10% povidone-iodine and 0.2% BAC showing particularly strong RDEs. The RDE of 0.2% BAC was strong enough to reduce the median survival times of severe acute respiratory syndrome coronavirus-2, human coronavirus-OC43, and influenza virus from 670 to 5.2, 1300 to 12, and 120 to 4.2 min, respectively. Additionally, this strong RDE was maintained even 4 h after coating the skin. Clinical data also showed that the strong RDE of 0.2% BAC was maintained for more than 2 h. Thus, applying disinfectants with strong RDEs on the skin correlates with a reduction in virus survival time and appears to create a skin surface environment that is not conducive to virus survival. A prolonged reduction in virus survival decreases the contact transmission risk, thereby enabling stronger infection control.

Background. In recent years, interest in the use of barrier methods of contraception has increased, since many women prefer them in connection with the change in the epidemiological situation associated with COVID-19, with contraindications to other methods of contraception, as well as with irregular sex life and casual sexual intercourse. In addition, these methods of contraception are preferred for breastfeeding mothers and pre- and postmenopausal women. Studies of the efficacy of spermicidal agents in late reproductive age women have not previously been carried out, although their use in this population is of particular interest, since these agents do not have a systemic effect and, if used correctly, can prevent unwanted pregnancies. The article presents data from an international French-Russian study of the efficacy of spermicides containing benzalkonium chloride in late reproductive age women (over 40 years). The study was carried out on the basis of 7 private offices of obstetricians and gynecologists in France and 6 obstetric and gynecological clinics in Russia. Aim. Assessment of the contraceptive efficacy, safety and acceptability of a cream containing benzalkonium chloride in women over 40 years of age. Materials and methods. The study included non-pregnant women aged 40 and over who had at least 1 menstrual period in the past 3 months and who would like to use spermicides as contraception for at least 6 months. After a 6-month period of mandatory use of spermicide, patients could, if desired, continue to use it for the next 6 months. All women were given Pharmatex (1.2%), a vaginal cream containing benzalkonium chloride (1.2 g per 100 g of cream) as the active ingredient, 1 standard dose before each intercourse. The primary endpoint was the Pearl Index. The acceptability of the method after each use of the cream, the moisturizing effect, and the woman's and researcher's overall satisfaction with this method of contraception were also assessed. Safety was assessed using adverse event monitoring. Results. An analysis of efficacy of the study drug showed that during study, pregnancy did not occur in any of the women. Pearl Index for 12 months was 0. Over the mandatory 6-month period, the use of Pharmatex cream was assessed by patients as acceptable (to some extent acceptable, acceptable, completely acceptable) in 98% of sexual intercourse, and over the 12-month period in 98.6% of intercourse. The moisturizing effect of the cream was noted by 96.1% of women. In 6 months of the use of Pharmatex cream, overall satisfaction was rated as quite good, good, or very good by 99.3% of patients and in 12 months by 100% of patients. Adverse events were noted only in 0.5% of cases. Most of these events were assessed as unrelated to the study drug. Conclusion. The use of a benzalkonium chloride spermicidal cream can be considered an effective and acceptable method of contraception for women over the age of 40. It is well tolerated, has a moisturizing effect on the vaginal mucosa, and meets the needs and lifestyle of women. The contraceptive with benzalkonium chloride has a favorable safety profile: it does not adversely affect the normal flora of the vagina, can be used during breastfeeding, since it does not penetrate into the vascular bed and doesnt have systemic effects.

To evaluate the noninferiority of intraocular pressure (IOP)-lowering latanoprost without benzalkonium chloride (BAK) versus latanoprost with BAK (for treatment of open-angle glaucoma or ocular hypertension).Overall, 578 patients were randomized 1:1 to latanoprost without BAK or latanoprost with BAK once daily in the affected eye(s) for 12 weeks. The primary efficacy endpoint was IOP, measured on days 0, 7, 28, 56, and 84 (8 am, 10 am, and 4 pm). Noninferiority was established if the following criteria were met: 95% confidence interval (CI) of the mean difference between treatments included 0 mm Hg for all time points (N1), 95% CI upper limit less than 1.5 mm Hg (N2), and less than 1 mm Hg for≥7 of 12 time points (N3). Primary efficacy analysis was performed on the intent-to-treat population. Safety measurements included ocular and systemic adverse event (AE).The 95% CI included 0 mm Hg for 7/12 time points (N1), 95% CI upper limit was less than 1.5 mm Hg for 12/12 time points (N2), and less than 1.0 mm Hg for 4/7 time points (N3). AEs were mild and similarly distributed between groups.Latanoprost without BAK did not meet two of three criteria for noninferiority and showed a similar safety profile relative to latanoprost with BAK.

This study aimed to achieve an in vitro quantification of the effects of composition and formulation factors on the killing rates of alcohol-based hand sanitizers. The killing rates of 85% ethyl alcohol (ET) and isopropyl alcohol (IPA) were studied under different conditions such as pH, electrolyte concentration, or inclusion of herbal extracts (cucumber, carrot, and aloe vera), a quaternary ammonium compound, or thickener over different time intervals. Changes in the activities were retested after 3 months as an indication of stability. From two-way ANOVA, both the time of exposure and the sanitizer type affected the activity against Staphylococcus aureus (P = 0.001 for both alcohols), whereas for Escherichia coli, time of exposure was significant (P = 0.027), while sanitizer type was less significant (P = 0.063). Extreme pHs, the presence of ions, and the inclusion of additives such as benzalkonium chloride (BAC), plant extracts, or carbomer impacted the 3-month activity of the samples differently. Important differences existing in the activities of ET and IPA, as a function of formulation factors or use conditions have been quantified using in vitro methods. Formulations should best be tailored for particular purposes and the all-purpose hand sanitizer may not exist. Graphic Abstract

Biocides used as disinfectants are important to prevent the transmission of pathogens, especially during the current antibiotic resistance crisis. This crisis is exacerbated by phenotypically tolerant persister subpopulations that can survive transient antibiotic treatment and facilitate resistance evolution. Here, we show that E. coli displays persistence against a widely used disinfectant, benzalkonium chloride (BAC). Periodic, persister-mediated failure of disinfection rapidly selects for BAC tolerance, which is associated with reduced cell surface charge and mutations in the lpxM locus, encoding an enzyme for lipid A biosynthesis. Moreover, the fitness cost incurred by BAC tolerance turns into a fitness benefit in the presence of antibiotics, suggesting a selective advantage of BAC-tolerant mutants in antibiotic environments. Our findings highlight the links between persistence to disinfectants and resistance evolution to antimicrobials., Phenotypically tolerant, persister bacterial subpopulations can survive transient antibiotic treatment and facilitate resistance evolution. Here, Nordholt et al. show that E. coli can display persistence against a widely used disinfectant and this is associated with alterations in the cell surface and with antibiotic tolerance.

Environmental DNA (eDNA) analysis allows noninvasive and cost-effective monitoring of macroorganisms' distribution and composition in aquatic ecosystems. Benzalkonium chloride (BAC) is an inexpensive and simple preservative for eDNA in water samples and has been used in many eDNA studies for preventing its degradation during transportation. However, its preservation performance has limitedly been evaluated by species-specific assays, targeting short fragments of mitochondrial DNA in freshwater and brackish ecosystems. Here, we examined the performance of BAC in preserving eDNA in seawater samples, targeting different fragment lengths of mitochondrial and nuclear eDNA, and community information inferred by eDNA metabarcoding. We quantified the time series changes of Japanese jack mackerel (Trachurus japonicus) eDNA concentrations in experimental tanks and inshore seawater to compare the yields and decay rates of eDNA between BAC treatments. For both tank and field samples, BAC treatment substantially suppressed the degradation of all types of target eDNA and increased the eDNA yields at the start of the experiment. In addition, we performed eDNA metabarcoding targeting fish community to compare the species richness and composition in seawater samples between BAC treatments, showing that the number of fish species in field samples hardly varied throughout a day by BAC treatment. Our findings indicate high versatility of BAC in preserving both the quantitative (copy number) and the qualitative (species richness) information on various types of aqueous eDNA in various environmental conditions. BAC should therefore be used to minimize the false-negative detection of eDNA, regardless of target genetic regions, fragment sizes, environmental conditions, and detection strategies.

INTRODUCTION Quaternary ammonium compounds (QUATs) are commonly found in cleaning products, disinfectants, hand sanitizers, and personal care products. They have been used for >50 years and are considered safe when used according to directions. Recent papers report reduced fertility and neural tube defects in rodents after low-level exposures. To determine if QUATs interfere with mammalian reproduction and development, we conducted a methodical assessment of all available data. METHODS A systematic literature search identified 789 potential articles. Review of titles and abstracts found eight relevant studies, including two dissertation chapters; to these, 10 unpublished, guideline-compliant developmental and reproductive toxicity (DART) studies of QUATs (alkyldimethylbenzylammonium chloride [ADBAC] and dialkyldimethylammonium chloride [DDAC]) were added. ToxRTool was utilized to evaluate all 18 studies for data quality. RESULTS Six studies were scored as "reliable without restriction"; four studies were considered "reliable with restriction" (mainly due to small rabbit group sizes). No test article-related, adverse DART endpoints were reported in these studies. ToxRTool scored the remaining eight studies as "not reliable." The unreliable studies failed to fully describe methods and/or endpoints, did not quantify (and in some cases, did not verify) exposures, utilized non-standard test methods, reported endpoints incorrectly, and assessed endpoints at inappropriate times. Some (not all) unreliable studies reported adverse effects after 7.5 mg QUATs/kg/day (mice), but these results were inconsistent. The reliable studies tested exposures ≥100 mg/kg/day (rats) with no effects. CONCLUSIONS The available weight of evidence indicates no adverse DART effects after QUATs exposures at anticipated concentrations and normal use.

Purpose — to analyze the literature data on the benefits of preservative-free medication therapy for glaucoma.Materials and methods. 482 articles in the Pubmed database published from 1975 to 2020 were analyzed using the terms: “glaucoma”, “preservatives”, “preservative-free therapy”, “benzalkonium chloride”. The review includes 78 articles. Inclusion criteria: studies that examined the effect of local antihypertensive therapy on the condition of the ocular surface in comparison with preservative-free drugs.Discussion. BAC is the most common preservative used in ophthalmology, accounting for 70 % of eye drop formulations. But it has a pronounced toxic effect on the ocular surface, so other classes of preservatives have been developed. These include polyquaternium-1 detergent; oxidizing preservatives — stabilized oxychlorocomplex and sodium perborate; ionic buffer preservative. However, most of the publications are devoted to BAC, as it is considered the most toxic and, at the same time, the most commonly used preservative. There is a large number of switching studies from preservative therapy to preservative-free, in which almost all groups of drugs used for the treatment of glaucoma were studied, but the use of antihypertensive drugs is associated not only with the action of preservatives, but also with the active substance, excipients and buffers. However, most switching studies demonstrate the benefits of preservative-free drugs. Other studies compared preservative and preservative-free drugs with the same active ingredients, in which a comparable hypotensive effect and safety profile was revealed, which indicates that BAC is not required for adequate penetration of the active substance to the point of application. At the same time, statistically significant advantages in the tolerability of preservativefree therapy were also revealed.Conclusion. Glaucoma preservative therapy has a toxic effect on the ocular surface, which leads to a decrease in the quality of life and compliance. Switching to preservative-free drugs can help reduce iatrogenic complications during long-term treatment of patients with glaucoma

In the biomonitoring using environmental DNA (eDNA) analysis, the suppression of eDNA degradation has been an important issue to estimate accurately the presence of target species and their eDNA concentrations. A recently proposed eDNA preservation technique requires only the addition of benzalkonium chloride (BAC) to water samples and has been used for various studies as an alternative solution to on-site filtration. However, BAC remaining in filters may adsorb to and inhibit the function of the enzyme used to extract eDNA from filters. In this study, we tested whether eDNA yield is affected by BAC addition immediately before filtration and demonstrated that the BAC in water remaining in filters decreased the eDNA yield significantly. We found that simple pre-centrifugation is effective for removing the remaining water from the filters to prevent the eDNA yield reduction due to the use of BAC. This is the most important finding in the present study. Appropriate eDNA extraction techniques are needed when BAC is used to secure eDNA yields and expand the application of eDNA analysis for biomonitoring.

Bentonite clays exhibit high adsorptive capacity for contaminants and is frequently used as a feed additive to reduce the bioavailability and thus the toxicity of several mycotoxins. Zearalenone (ZEN) is a secondary Fusarium toxic metabolite that can contaminate a wide range of food- and feedstuff. Since organophilic treatments is known to increase the adsorption capacity of bentonites, the aim of study was to evaluate and compare the ability of natural bentonite and bentonite treated with BAC302 to protect against ZEN-induced cytotoxicity in the epithelial colorectal adenocarcinoma (Caco-2) and human leukemia monocytic (THP-1) cell lines. The two materials were not toxic to the cell lines at lower concentrations. Furthermore, the results indicate that the two materials protect the Caco-2 and THP-1 cells against ZEN-induced cytotoxicity, probably by extracellular adsorption of ZEN. The tested natural bentonite shows potential for in vivo testing to evaluate if it is suitable for intoxication in ZEN contaminated animal feeds.

Purpose Preservatives are essential for preventing contact lens (CL)-related microbial keratitis (MK). The purpose of this review is to summarize the current knowledge related to the use of common ophthalmic preservatives in CL care products with respect to both safety and efficacy. Methods Manuscripts written in English were obtained by searching PubMed.gov with the term contact lens plus antimicrobial, benzalkonium chloride, biguanide, Aldox, polyquaternium, preservative, thimerosal, EDTA (ethylenediaminetetraacetic acid), chlorhexidine, or blister pack. Results This review found that first-generation preservatives are no longer used in CL multipurpose solutions (MPS) due to their high levels of ocular toxicity. Modern, high-molecular-weight preservatives, including polyquaternium-1 (PQ-1) and biguanides (PHMB), are generally effective against bacteria, minimally effective against fungi, and not effective against Acanthamoeba. PQ-1 and PHMB are likely safe when used with CLs, but they may cause ocular adverse events, with roughly equal risk between the two preservatives. Some CL MPS contain both PQ-1 and PHMB, but no increased risk of adverse events has been reported when combining the two. Hydrogen-peroxide (H2O2) solutions are effective against all common ocular microbes, including Acanthamoeba, and they have been proven safe with proper compliance. Povidone-iodine (P-I) solutions are not currently commercially available in North America, but they have been shown in other countries to be safe and effective. Conclusion Patients should be monitored when using PQ-1 or PHMB-containing solutions since they have been associated with ocular adverse events. If events are detected, patients should be switched to an alternative solution. H2O2 or P-I solutions are preferred for any patient who may expose their CLs to water because they are the only solution categories effective against Acanthamoeba.

BACKGROUND Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung’s disease. Studies using animal models on the pathogenesis of HAEC are limited. Thus, this study aimed to establish a rat model of HAEC using topical application of 0.1% benzalkonium chloride (BAC) in the sigmoid colon. METHODS 55 male Sprague Dawley rats aged 10−12 weeks old were separated into 11 groups. The control group (n = 5) was euthanized on day-7, and the other 10 groups (n = 5 in each group) treated with 0.1% BAC in the sigmoid colon for 15 min to induce Hirschsprung’s disease were euthanized on day-7, -10, -12, -14, -17, -19, -21, -23, -25, and -28. The sigmoid colon was excised, fixed in formalin, and sectioned for histological examinations with hematoxylin and eosin staining. The degree of HAEC was compared within all groups. RESULTS Rats that were sacrificed on day-7 to -12 showed the 1st degree or early HAEC, which was most likely caused by BAC application. The 2nd degree of HAEC occurred in rats that were sacrificed on day-14 that showed a macrophage infiltration in the sigmoid colon, thus fulfilled the initial criteria for HAEC (p = 0.0025 versus control). The degree of enterocolitis increased with time, and the highest degree was found in rats that were sacrificed on day-28 (p

PURPOSE To investigate whether contact lenses used after surgery for congenital cataracts act as a depot for dexamethasone, which would allow the prescribed amount of drops to be reduced, and to examine whether the preservative benzalkonium chloride accumulates in the contact lens matrix, which would suggest a need for more frequent replacements. METHODS Contact lenses (n = 10) worn by infants treated with dexamethasone eye drops after congenital cataract surgery were analysed with scanning electron microscopy, UV-vis, 1 H-NMR and LDI-MS for chemical deposits and for changes on the contact lens surface. Unused lenses (n = 5) and lenses (n = 4) from patients with no eye drop treatment were analysed as reference. RESULTS The treated contact lenses displayed ruptured surfaces in comparison with unused and reference lenses. Dexamethasone and BAK were not detected in any of the lenses. A polyethylene oxide component was found in the treated lenses, likely originating from the dexamethasone eye drops or the contact lens solution. CONCLUSION Dexamethasone and BAK do not accumulate in the contact lenses, and a depot effect of any clinical significance is unlikely. Therefore, the number of drops given after surgery should remain the same regardless of whether the child has contact lenses. The ruptured surface may both decrease the child's comfort and increase the risk of microbial adhesion, and so it is recommended that contact lenses should be replaced once a month throughout the course of anti-inflammatory eye drop treatment after surgery for congenital cataract.

Purpose The multi-instillation of three commercially available (CA) eye drops [fluorometholone (FL)-, bromfenac (BF)- and levofloxacin (LV)-eye drops] has been used to manage pain and inflammation post-intraocular surgery. However, the multi-instillation of these three eye drops causes corneal damage, and the FL drops have the disadvantage of low ocular bioavailability. To overcome these problems, we prepared fixed-combination eye drops based on FL nanoparticles (FL-NPs) and BF/LV solution (nFBL-FC), and evaluated the corneal toxicity and transcorneal penetration of the nFBL-FC eye drops. Methods FL powder was mixed in 2-hydroxypropyl-β-cyclodextrin solution containing benzalkonium chloride, mannitol and methylcellulose, and milled with a Bead Smash 12 (5500 rpm for 30 s×30 times). The BF/LV solution was then added to the milled-dispersions to be used as nFBL-FC. The FL, BF and LV concentrations were measured by HPLC methods, and transcorneal penetration was evaluated in rabbits. Results The FL particle size in nFBL-FC was 40–150 nm, with only 0.0018% in liquid form. No aggregation of FL particles in the nFBL-FC was observed for 1 month. The viability of human corneal epithelial cells treated with nFBL-FC was remarkably higher than that of cells subjected to the multi-instillation of the corresponding three CA-eye drops. In addition, the corneal penetrations (AUC) of the FL, BF and LV in nFBL-FC were 4.9-, 1.8-, and 7.1-fold those of the corresponding CA-eye drops, respectively. Moreover, the caveolae-dependent endocytosis (CavME) inhibitor (nystatin) significantly prevented the transcorneal penetration of these drugs. Conclusion We prepared fixed-combination eye drops based on FL-NPs and BF/LV solution (nFBL-FC), and show that high levels of FL-NPs and dissolved BF/LV (liquid drugs) can be delivered into the aqueous humor by the instillation of nFBL-FC. Further, we show that CavME is mainly related to the enhancement of transcorneal penetration of both the solid (NPs) and liquid drugs., Graphical Abstract Scheme for corneal penetration after the instillation of nFBL-NPs. Abbreviations: CavME, caveolae-dependent endocytosis; CME, clathrin-dependent endocytosis; nFBL-FC, fixed-combination eye drops based on fluorometholone nanoparticles and bromfenac/levofloxacin solution.

Benzalkonium chloride (BAC) is used as a preservative in eyedrops but induces subconjunctival fibrosis that can result in failure of glaucoma surgery. Tenon’s capsule fibroblasts in subconjunctival tissue interact with the corneal epithelium through tear fluid. With the use of a coculture system, we have now investigated the effect of human corneal epithelial (HCE) cells on myofibroblastic transdifferentiation of human Tenon fibroblasts (HTFs) induced by BAC (5 × 10−6%). Immunofluorescence and immunoblot analyses revealed that the BAC-induced expression of α smooth muscle actin (αSMA) in HTFs was suppressed by coculture of these cells with HCE cells (p p p p

Introduction: Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. Methods: Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol® (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. Results: All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; p = 0.93), 71% for DS (0.0075% BAK; p = 0.067), 70% for OP (0.01% BAK; p = 0.054), and 69% for LT (0.02% BAK; p = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (p = 0.217), 52% for DS (p = 0.011), 34% for OP (p = 0.017), and 31% for LT (p = 0.0007). Conclusion: LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding.

Preservatives in multidose formulations of topical ophthalmic medications are crucial for maintaining sterility but can be toxic to the ocular surface. Benzalkonium chloride (BAK)—used in approximately 70% of ophthalmic formulations—is well known to cause cytotoxic damage to conjunctival and corneal epithelial cells, resulting in signs and symptoms of ocular surface disease (OSD) including ocular surface staining, increased tear break-up time, and higher OSD symptom scores. These adverse effects are more problematic with chronic exposure, as in lifetime therapy for glaucoma, but can also manifest after exposure as brief as seven days. Multiple strategies are available to minimize or eliminate BAK exposure, among them alternative preservatives, preservative-free formulations including sustained release drug delivery platforms, and non-pharmacological therapies for common eye diseases and conditions. In this paper, we review the cytotoxic and clinical effects of BAK on the ocular surface and discuss existing and emerging options for ocular disease management that can minimize or eliminate BAK exposure.

Background To compare the effect of two different prostaglandin analogues (Travatan® vs. Xalatan®) on ocular surface parameters. Methods This study includes 44 eyes of 44 patients with newly diagnosed primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Patients were randomly divided into two groups and treated with either benzalkonium chloride (BAK)-preserved latanoprost and polyquad-preserved travoprost. Changes in intraocular pressure (IOP) levels and ocular surface parameters including ocular surface disease index (OSDI) questionnaire, tear break-up time (TBUT), ocular surface staining scores, and Schirmer test scores of patients were performed at baseline, 1, 3, 6 and 12 months of treatment and compared. Results The age, sex ratio, visual acuity, central corneal thickness, and cup/disc ratio were similar between the groups. A decrease in IOP levels (23.3 ± 2.5 to 15.5 ± 2.3), TBUT (5.5 ± 2.3 to 4.1 ± 1.7 sec), Schirmer test values (11.3 ± 5.9 to 8.6 ± 4.7 sec), and a worsening in OSDI scores (44.6 ± 15.2 to 55.1 ± 13.1) and staining scores (1.7 ± 1.6 to 2.3 ± 1.8) were observed in all patients in the first month of treatment (p

Purpose: This study was undertaken with an objective to compare the aqueous humor pharmacokinetics (PKs) of bimatoprost and bimatoprost free acid of innovator bimatoprost 0.01% (BAK-Bimatoprost) and the novel formulation, Tight Junction Modulation technology based bimatoprost 0.01% (TJM-bimatoprost) containing polyhexamethylene Biguanide hydrochloride (PHMB) as a preservative. Materials and Methods: All animals in the study were assigned to one of two treatment arms: either a single dose of BAK-Bimatoprost (n=28) or a TJM-bimatoprost ophthalmic solution (n=28). Time points for aqueous humor collection were 0.5, 1, 2, 4, 8, 12 and 24 Hrs after drug administration. Results: The mean Cmax of 11.93± 2.70 vs 10.92± 3.84 ng/ml was comparable (P>0.05, one-way ANOVA) across TJM bimatoprost and BAK-bimatoprost treatment arms. Results of other PK parameters pertaining to bimatoprost+ bimatoprost free acid concentration were as follows: time to maximum concentration (T_max) was 1.75± 2.0 vs 1.50 ± 1.16 hr and half-live (T_half) was 2.13 ± 0.58 vs 2.47 ± 0.79 hr in the TJM- bimatoprost and BAK-bimatoprost treatment arms respectively. Overall, there was no difference between TJM-bimatoprost and BAK-bimatoprost treatment arms in the PK end points. Conclusions: The results taken in totality support the hypothesis that pharmacokinetics TJM-bimatoprost 0.01%, containing PHMB preservative, is comparable to BAK-bimatoprost 0.01%. Key messages: A new formulation of bimatoprost 0.01% using Tight Junction Modulation technology is pharmacokinetically comparable to marketed formulation of bimatoprost containing benzalkonium chloride preservative. Keywords: Aqueous humor, Bimatoprost 0.01%, Gel free reservoir technology, Glaucoma, Pharmacokinetics, Polyhexamethylene biguanide, Tight junction modulator.

Purpose: To assess the effectiveness and tolerability of a new latanoprost 0.005% benzalkonium chloride (BAK)-free nanoemulsion. Methods: A nonrandomized multicenter study was conducted be...

The persistence of Stenotrophomonas maltophilia, especially in hospital environments where disinfectants are used intensively, is one of the important factors that allow this opportunistic pathogen to establish nosocomial infections. In the present study, we illustrated that S. maltophilia possesses adaptive resistance to the disinfectant benzalkonium chloride (BAC). This BAC adaptation was abolished in the ΔmfsQ mutant, in which a gene encoding an efflux transporter belonging to the major facilitator superfamily (MFS) was deleted. The ΔmfsQ mutant also showed increased susceptibility to BAC and chlorhexidine gluconate compared with a parental wild type. The expression of mfsQ increased upon exposure to quaternary ammonium compounds, including BAC. Thus, the results of this study suggest that mfsQ plays a role in both adaptive and nonadaptive protection of S. maltophilia from the toxicity of the disinfectant BAC.

This study aimed to investigate the association between biocides' reduced susceptibility and the presence of efflux pump genes including cepA, qacEΔ1 and qacE in multidrug-resistant (MDR) Pseudomonas aeruginosa. The MDR P. aeruginosa isolates were collected and identified from different clinical samples. The minimum inhibitory concentrations (MIC) of four biocides (chlorhexidine gluconate 1%, benzalkonium chloride 1%, Kohrsolin® extra, and SEPTI-Turbo) were determined by microbroth dilution with and without carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Polymerase chain reaction (PCR) was performed for detecting the efflux pump genes. In total, 92 MDR P. aeruginosa isolates were collected. The reduced susceptibility (8–128 µg/ml) was seen against chlorhexidine gluconate 1%, benzalkonium chloride 1%, Kohrsolin® extra, and SEPTI-Turbo in 63 (68.5%), 59 (64.1%), 64 (69.6%), and 65 (70.6%) isolates, respectively. The Kohrsolin® extra was the most effective biocide. The cepA, qacE, and qacEΔ1 were detected in 56 (60.9%), 1 (1.1%), and 34 (36.9%) isolates, respectively. There was a significant association between the presence of biocide resistance genes and reduced susceptibility to studied biocides (P = 0.00001). The CCCP had no effect on benzalkonium chloride 1% and Kohrsolin® extra, but reduced the MICs of chlorhexidine gluconate 1% and SEPTI- Turbo by 2 to 128 fold. The P. aeruginosa isolates exhibited varying degrees of tolerance to biocides. The cepA was the most prevalent gene. There was a significant connection between the occurrence of the efflux pump genes cepA and qacEΔ1 with reduced biocide susceptibility.

BACKGROUND Spermicides have been identified as a potentially attractive alternative to hormonal contraceptives and/or intrauterine devices. Thus, this study aimed evaluating the efficacy and local tolerance of benzalkonium chloride (BKC) and myristalkonium chloride (MKC) contained in Pharmatex® vaginal formulations and compare them with nonoxynol-9 (N-9), the most common active ingredient in topical vaginal contraceptives. METHODS Human normozoospermic samples were assessed for motility, viability, acrosome status and penetration ability after exposure to control, N-9 or different BKC and MKC doses for 0 and 10 minutes. Local tolerance on HeLa cells was evaluated by the Trypan-blue and MTT assays. RESULTS Exposure to BKC and MKC reduced acrosome integrity while promoting total immobilisation and complete loss of sperm viability (p

The aim of the study was to evaluate the effectiveness of the preparations Optinol® Express Moisture (0.21 %) and Optinol® Deep Moisture (0.4 %) in the treatment of children with dry eye syndrome (DES) and to determine the indications for prescribing these drugs for various etiologies and clinical course of the disease.Patients and methods. The study involved 56 children aged 4–17 years with DES, which were divided into 3 groups, depending on its pathogenetic type. The first consisted of 24 children with DES, which developed on the basis of chronic blepharitis, the second — 12 children with neuroparalytic keratitis, and the third — 18 children with chronic uveitis, in whom DES was caused by prolonged instillations of eye drops with benzalkonium chloride. Each group was divided into 2 more equal subgroups, the first of which was prescribed the drug Optinol® Express Moisture, and the second — Optinol® Deep Moisture with a frequency of 4 times a day.Results. In all children, from the very first days of instillation of the studied drugs, a decrease in the severity of subjective signs of DES (OSDI) was noted, as well as a gradual decrease in the degree of xerotic changes in the ocular surface (severity of its staining with vital dyes) and an increase in the stability of the tear film (M.Norn). At the same time, the positive dynamics of the controlled parameters increased with the continuation of therapy, reaching a maximum by the 30th day of treatment. Moreover, the effectiveness of therapy depended on the severity of xerosis of the ocular surface: it was maximal in children with mild, and minimal in children with an extremely severe form of xerosis (with neuroparalytic keratitis). Moreover, the drug Optinol® Express Moisture was more effective in the treatment of children with mild and extremely severe forms of DES, and Optinol® Deep Moisture — with moderate and severe xerosis.Conclusion. The preparations Optinol® Express Moisture and Optinol® Deep Moisturization are effective in the treatment of children with DES, which has developed on the basis of pathology of the ocular surface of neurotrophic and artifact genesis, as well as increased volatility of the precorneal tear film against the background of chronic blepharitis.

The main corneal infections reported worldwide are caused by bacteria and viruses but, recently, the number of Acanthamoeba keratitis (AK) cases has increased. Acanthamoeba genus is an opportunistic free living protozoa widely distributed in environmental and clinical sources, with two life-cycle stages: the trophozoite and the cyst. AK presents as primary symptoms eye redness, epithelial defects, photophobia and intense pain. An early diagnosis and an effective treatment are crucial to avoid blindness or eye removal but, so far, there is no established treatment to this corneal infection. Diverse research studies have reported the efficacy of commercialized eye drops and ophthalmic solutions against the two life cycle stages of Acanthamoeba strains, that usually present preservatives such as Propylene Glycol of Benzalkonium chloride (BAK). These compounds present toxic effects in corneal cells, favouring the inflammatory response in the so sensitive eye tissue. In the present work we have evaluated the efficacy of nine proprietary ophthalmic solutions with and without preservatives (ASDA Dry Eyes Eyedrops, Miren®, ODM5®, Ectodol®, Systane® Complete, Ocudox®, Matrix Ocular®, Alins® and Coqun®) against the two life cycle stages of three Acanthamoeba strains. Our work has demonstrated the high anti-Acanthamoeba activity of Matrix Ocular®, which induces the programmed cell death mechanisms in Acanthamoeba spp. trophozoites. The high efficacy and the absence of ocular toxic effects of Matrix Ocular®, evidences the use of the Arabinogalactan derivatives as a new source of anti-AK compounds., Graphical abstract Image 1

Purpose: The aims of this work were a) to describe the histology of the lacrimal gland (LG) and cornea induced by an adenovirus (Ad) vector encoding the human erythropoietin (Epo) gene delivered to...

Interleukin-1 receptor antagonist (IL-1Ra) is an active pharmaceutical ingredient obtained by the method of gene transformation of Escherichia coli, provides a neuroprotective effect, namely – inhibition of oxidative modification of proteins, normalization of functional activity of mitochondrial energy, mitochondrial energy. Early complex physical-chemical, microbiological, and biopharmaceutical studies have developed a new intranasal formulation, the formulation of which contains: IL-1Ra, sodium carboxymethyl cellulose, D-panthenol, benzalkonium chloride, trilon B, Tween-80, phosphate buffer solution. Given the peculiarities of the technological process, when creating a new gel dosage form, it is necessary to justify the temperature of the carrier base, the introduction of the active substance into the base, as well as to predict the possible chemical interaction of individual components in the dosage form. Therefore, the application of thermogravimetric analysis in pharmaceutical technology is relevant. The aim of the work is to conduct thermogravimetric studies of a new nasal form with an antagonist of interleukin-1β (IL-1Ra). Materials and methods. The objects of thermogravimetric studies were: semi-finished product-solution of the receptor antagonist of interleukin-1 (IL-1Ra). Excipients were: sodium carboxymethylcellulose, tween-80, D-panthenol, trilon B, benzalkonium chloride. To ensure the appropriate pH value used phosphate buffer solution (pH 6.0), according to the recipe to State Pharmacopoeia 2 ed. In addition to the individual components of the finished nasal gel, also prepared nasal gel without IL-1Ra, as well as gel with IL-1Ra. The thermographic analysis was performed on a derivatograph – Shimadzu DTG-60 (Japan) with a platinum-platinum-rhodium thermocouple when heating the samples in aluminum crucibles (from 15 °C to 250 °C). Al2O3 was used as a reference substance. The heating rate was 10 °C per minute. The weight of the test samples ranged from 19.22 mg to 52.91 mg. The derivatograph graphically recorded the obtained data in the form of curves T, DTA, TGA. The T curve on the derivatogram shows the change in temperature, and the TGA curve shows the change in mass of the sample during the study period. The DTA curve reflects the differentiation of thermal effects, contains information about endothermic and exothermic maxima, can be used for qualitative evaluation of the derivatogram. Results. The study consisted of two stages. At the first stage, we studied the derivatograms of experimental samples – individual ingredients of the finished nasal gel - active and excipients, namely: IL-1Ra, sodium carboxymethylcellulose, tween-80, D-panthenol, trilon B, benzalkonium chloride, phosphate buffer solution 6.0. In the second stage, samples of nasal gels were prepared: nasal gel with the required amount of excipients, in addition to the active substance – IL-1Ra, as well as a nasal gel containing IL-1Ra and the required amount of excipients. As a result, we obtained some parameters of thermogravimetric analysis in the form of a graphical image – derivatograms, which were then analyzed. Conclusions. Thermogravimetric studies of individual components of nasal gel with IL-1Ra, as well as nasal gels with active substance and without active substance, were found that the manufacturing process of gel with IL-1Ra should be carried out taking into account thermolabile compounds. First, you need to prepare the base without preservative and IL-1Ra. Then at a temperature not exceeding 40 °C dissolve the preservative, and then when cooled to 20 °C add IL-1Ra. It was found that the developed dosage form of the gel with IL-1Ra is a mixture of active and excipients, the ingredients of which do not interact with each other and can be combined in one dosage form.

Benzalkonium chloride is a concern because of its widespread use combined with environmental impacts. It has been found throughout the built and natural environment in wastewater influent, effluent...

The interaction between CoII and 5-methyl-4-(2-thiazolylazo)-resorcinol (MTAR) was studied in a water-chloroform system, in the presence or absence of benzalkonium chloride (BZC) as a cationic ion-association reagent. The optimum pH, concentration of the reagents and extraction time for the extraction of Co were found. In the presence of BZC, the extracted ion-associate could be represented by the formula (BZ+)[CoIII(MTAR2–)2], where MTAR is in its deprotonated form. The following extraction-spectrophotometric characteristics were determined: absorption maximum, molar absorptivity, Sandell’s sensitivity, limit of detection, limit of quantification, constant of extraction, distribution ratio and fraction extracted. In the absence of BZC, the extraction is incomplete and occurs in a narrow pH range. The extracted chelate contains one deprotonated and one monoprotonated ligand: [CoIII(MTAR2–)(HMTAR–)].

Antiseptic wound ointments are widely used to treat dermal wounds that are microbially contaminated. Polygalacturonic acid (PG)+caprylic acid (CAP) is a novel combination that has been shown to eradicate biofilms. We developed a novel PG+CAP ointment and compared the biofilm eradication capability and cytotoxicity of PG+CAP with that of commercially available antiseptic wound ointments. We used a well-established biofilm model to quantitatively assess the eradication of organisms following exposure to the wound ointments for 2 hours. PG+CAP ointment completely eradicated Candida albicans, multidrug-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus biofilms, whereas MediHoney, polyhexamethylene biguanide (PHMB), and benzalkonium chloride (BZK) ointments failed to eradicate all biofilms within 2 hours. We assessed cytotoxicity by exposing L-929 fibroblasts to extracts of each ointment; Trypan blue exclusion was used to assess cell viability, and Alamar blue conversion was used to assess metabolic function. After exposure to PG+CAP and MediHoney, fibroblast viability was 96.23% and 95.23%, respectively (Trypan blue), and was comparable to untreated cells (98.77%). PHMB and BZK showed reduced viability (83.25% and 77.83%, respectively, p < 0.05 ). Metabolic activity results followed a similar pattern. Cytotoxicity of PG+CAP ointment towards erythrocytes was comparable to saline. PG+CAP ointment seems to be safe and can rapidly eradicate microbial biofilm; thus, PG+CAP ointment merits further in vivo testing as a potential antimicrobial wound ointment.

In agreement with the recent trend of consumers’ demand for natural antimicrobial products, the importance of using natural compounds in food is increasing. Among numerous natural compounds, grapefruit seed extract (GSE) is widely known for its extremely effective antimicrobial activity. The direct use of GSE in food is the most common method of application. Other GSE applications exist using it with coating materials and incorporating it into edible films. Previously done studies identified benzalkonium chloride, benzethonium chloride, and other synthetic agents from GSE. Unfortunately, the presence of these antibacterial contents does not exactly coincide with the natural aspects of GSE. Even though GSE is identified as a natural antimicrobial, this observation suggests that the GSE antibacterial activity is derived from these synthetic substances such as benzalkonium chloride. Therefore, further research is needed about these controversial issues. This review analyzed the application of GSE as a natural antimicrobial in the food industry and suggested further research directions.