Cell death and barrier disruption by clinically used iodine concentrations.

Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I2), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I2 Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits.

Reducing Vaccinia virus transmission indoors within 60 seconds: Applying SAFEAIR-X aerosol with Iodine-V as a disinfectant.

Iodine-V ((C26H39N4O15)x * (I2)y) demonstrates an in vitro virucidal activity by deactivating SARS-CoV-2 viral titers. It combines elemental iodine (I2) and fulvic acid (C14H12O8), forming a clathrate compound. The antiviral properties of Iodine-V reduce viral load in the air to inhibit viral transmission indoors. This antiviral property was applied to form a disinfectant solution called SAFEAIR-X Aerosol. The current study evaluates the antiviral efficacy of Iodine-V in aerosol form in a prototype called SAFEAIR-X Aerosol. The experiment measured the antiviral efficacy of SAFEAIR-X following exposure to the Vaccinia virus (VACV) samples as a confirmed surrogate for SARS-CoV-2. The SAFEAIR-X showed 96% effectiveness, with 2 seconds of spraying duration and 60 seconds of contact time releasing less than 0.0001 ppm of iodine into the air, and a log reduction value of 1.50 at 60 seconds in 2 out of 3 tests was observed. Therefore, this study demonstrates SAFEAIR-X aerosol as a potential indoor surface and air disinfectant.

New In Situ-Generated Polymer-Iodine Complexes with Broad-Spectrum Antimicrobial Activity.

Iodine-containing systems show broad antiseptic properties that can be an invaluable tool in controlling infections in humans and animals. Here, we describe the first proof-of-concept studies on biocidal active polyamide- and polyurethane-iodine complexes that are produced in situ directly during the fabrication and/or polymerization process at laboratory and commercially relevant scales. These polymer-iodine materials are active against a broad range of microorganisms, including bacteria and fungi. It is suggested that the ease of manufacture and subsequent commercialization make said systems especially suited for applications as base materials for medical devices to reduce infection risks and control the spread of pathogens. IMPORTANCE Infectious diseases are of mounting medical and public concern. A major contributor to this trend is the proliferation of medical implants, which are inherently vulnerable to microbial contamination and the subsequent onset of hospital-acquired infections. Moreover, implant-associated infections in humans are often difficult to diagnose and treat and are associated with substantial health care costs. Here, we present the development of biocidal active polyamide- and polyurethane-iodine complexes that are generated in situ during fabrication. We show that the excellent antiseptic properties of water-soluble povidone-iodine can be similarly realized in water-insoluble engineering plastics, specifically polyamide- and polyurethane-iodine. These complexes have inherent biocidal activity against major pathogenic bacteria and fungi.

Molecular iodine is not responsible for cytotoxicity in iodophors.

BACKGROUND: Ten percent povidone-iodine (PVP-I) was initially promoted as 'tamed iodine' as the chemical activity of the active biocide, uncomplexed or free molecular iodine (I2), is reduced 30- to 50-fold compared with Lugol's solution. The idea that I2 is responsible for topical iodine staining and irritation remains widely held. However, there are no controlled studies that characterize the cytotoxicity and staining of the hydrophobic I2 species compared with the other hydrophilic iodine species that comprise over 99.9% of the total iodine in topical iodine disinfectants. AIMS: To compare the staining properties of the I2 species with other topical iodine disinfectants; to evaluate if the concentrations of I2 in diluted PVP-I used to reduce severe acute respiratory syndrome coronavirus-2 in the nasal cavity are potentially cytotoxic; and to determine if high concentrations of I2 can be delivered beyond the stratum corneum into the hypodermis, which could provide a mechanistic rationale for I2 out-gassing. METHODS: Five liquid compositions that contained complexed and uncomplexed (free) I2 in aqueous and non-aqueous carriers were used to evaluate the interaction of I2 with mammalian cells in culture as well as human and pig skin. FINDINGS: Concentrations of I2 (7800 ppm) that are 1500 times higher than that found in PVP-I can be applied to skin without irritation and staining. I2 is not cytotoxic at concentrations >100 times higher than that found in PVP-I, and does not contribute materially to staining of skin at concentrations found in Lugol's solution (approximately 170 ppm). I2 can partition into hypodermis tissue, remain there for hours and out-gas from skin. PVP-I and Lugol's solution are highly effective topical disinfectants, but do not facilitate diffusion of I2 through the stratum corneum. CONCLUSION: The maximum concentration of I2 found in diluted PVP, approximately 25 ppm, is not cytotoxic or irritating. The potential clinical utility of I2 has been limited by incorporating this broad-spectrum biocide into acidic aqueous formulations that contain numerous chemical species that contribute toxicity but not biocidal activity. I2 can be delivered topically into hypodermis tissue without irritation.

An in vitro antiviral activity of iodine complexes against SARS-CoV-2.

Since the emergence of COVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determined In vitro anti-SARS-CoV-2 activity of oral formulations (syrup and capsule)of an Iodine-complex (Renessans). First, cell cytotoxicity of Renessans on the Vero cells was determined using MTT assay. Afterwards, the antiviral activity of Renessans was determined using viral inhibition assays and TCID50. For this, nontoxic concentrations of the Renessans were used. The results showed that Renessans is nontoxic to the cells up to 50 µg/mL. At 1.5 µg/mL concentration, SARS-CoV-2 production was significantly reduced to 101.43 TCID50 and 101.58 TCID50 for the syrup and capsule, respectively, as compare to virus infected control cells 106.08 TCID50 and we found the dose dependent inhibition of virus replication in the presence of Renessans. Renessans inhibited SARS-CoV-2 with an EC50 value of 0.425 µg/mL and 0.505 µg/mL for syrup and capsule, respectively. Furthermore, there was no virus detected at concentration of 50 µg/mL of Renessans. This study indicates that Renessans, containing iodine, have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.

In vitro efficacy of a copper iodine complex PPE disinfectant for SARS-CoV-2 inactivation.

Background: The ability to protect workers and healthcare professionals from infection by SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is of great concern. Hospitals, nursing homes and employers are adopting infection control strategies based on guidance from leading public health organizations such as the CDC, OSHA, FDA, and other government bodies. Certain hard surface disinfectants are effective against SARS-CoV-2 but are not suitable for use on skin or personal protective equipment (PPE) that comes into contact with skin. Furthermore, near-ubiquitous alcohol-based hand sanitizers are acceptable for use on skin, but they are not suitable for use on PPE. PPE, especially masks, are also commonly being used for longer durations than normal. There is a need for new products and techniques that can effectively disinfect PPE during wear time without having detrimental effects on surrounding skin. Clyraguard spray is a novel copper iodine complex designed to be used on non-critical PPE. Methods: In this study, the Clyraguard copper iodine complex was tested for its ability to inactivate SARS-CoV-2 in solution. Results: These data indicate the product to be effective in reducing SARS-CoV-2 titers in a time-dependent manner, with the virus being reduced below the detection limits within 30 minutes. Conclusions: These results suggest that Clyraguard may be an effective tool for mitigating cross-contamination of non-critical PPE that may come into contact with SARS-CoV-2.