Hexylresorcinol 2.5mg / Benzalkonium chloride 600microgram lozenges sugar free

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.

Abstract licence: CC BY

Dry eye disease (DED) is an emerging health issue affecting people worldwide. There have been rapid advances in the development of novel molecules and targeted therapies for the treatment of DED in the recent past. For testing and optimizing these therapies, it is necessary to have reliable experimental animal models of DED. One such approach is the use of benzalkonium chloride (BAC). Several BAC-induced DED models of rabbits and mice have been described in literature. BAC induces high levels of proinflammatory cytokines in the cornea and conjunctiva, along with epithelial cell apoptosis and reduction of mucins, which leads to tear film instability, thereby successfully simulating human DED. The stability of these models directs whether the treatment is to be applied while BAC is being instilled or after its cessation. In this review, we summarize the previously described BAC animal models of DED and present original data on rabbit DED models created using 0.1%, 0.15%, and 0.2% BAC administration twice daily for two consecutive weeks. The 0.2% BAC model sustained DED signs for 3 weeks, while 0.1% and 0.15% models sustained DED signs for 1-2 weeks after BAC discontinuation. Overall, these models look promising and continue to be used in various studies to investigate the efficacy of therapeutic drugs for DED treatment.

Abstract licence: CC BY-NC-SA

PURPOSE: Inclusion of the preservative benzalkonium chloride (BAC) in ophthalmic solutions is prevalent, despite the noted potential for exacerbating dry eye disease (DED). Whilst studies incorporating BAC have assessed its' effects as a mouse model of DED, the impact on limbal epithelia is under-studied. Our investigation aimed to comprehensively assess the impact of different BAC dosing regimens and their suitability as a mouse model of DED. METHODS: C57BL/6J mice (n = 72) were administered topical BAC (0.05-0.2%) over 7 days. Fluorescein staining, corneal smoothness index, and immuno-histological analyses were applied to determine architectural and cellular changes on the ocular surface following BAC treatment. The effect of BAC (0.0001-0.01%) on cultivated primary mouse corneo-limbal epithelial cells (CLECs) (n = 6) was examined using morphological and functional assays. RESULTS: goblet cells were decreased. BAC treatment also modulated K14 expression and distribution within the limbus. In cultured CLEC, BAC triggered cell contraction and vacuolation, increased LDH release and elevated cell necrosis by 4.1-fold. Concentrations of BAC as low as 0.0001% decreased colony formation. CONCLUSIONS: This study describes how exposing C57BL/6 mice to BAC induce some clinicopathological features of DED seen in humans, and therefore provides the foundations to explore the consequences on the ocular surface, particularly on limbal epithelia and its' stem cells.

Abstract licence: CC BY-NC-ND

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.

Abstract licence: CC BY

4-Hexylresorcinol (4HR) is amphiphilic organic chemical and auto-regulator for micro-organism. As 4HR administration induces the stress on the endoplasmic reticulum, 4HR changes protein folding. The application of 4HR inhibits NF-κB signal pathway and TNF-α production. In addition, 4HR administration increases VEGF, TGF-β1, and calcification associated proteins. As a consequence, 4HR administration increases angiogenesis and bone formation in wounded area. Strong anti-inflammatory reaction and capillary regeneration in diabetic model demonstrate that 4HR can be applied on many types of surgical wound.

Abstract licence: CC BY

Introduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED). Methods: -DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction. Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission. Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.

Abstract licence: CC BY-NC