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PubMed2002

Method for the measurement of the diffusion coefficient of benzalkonium chloride.

Biofilm formation on the optical ports of cameras and underwater sensors is the primary cause of their reduced useful deployment time. The use of a transparent hydrogel coating containing the cationic surfactant benzalkonium chloride has been shown to extend the deployment times for up to 12 weeks for these instruments. In order to predict the effective lifetime of these coatings it was necessary to obtain the diffusion coefficient of the benzalkonium chloride used in the coatings. Benzalkonium chloride can have different alkyl chain lengths ranging from C8H17 to C18H37 with chain length greatly affecting its chemical properties. The benzalkonium chloride materials investigated here were mixtures of C12H25 and C14H29 as well as C14H29 on its own. These materials were selected for their proven biofilm resistant qualities. The diaphragm diffusion cell technique was investigated for its applicability to the measurement of diffusion coefficients of molecules with surfactant properties and the ability to form micelles. The method was found to be satisfactory for the cationic surfactant benzalkonium chloride. The average value of the membrane cell integral diffusion coefficient D was 7.78 x 10(-6) cm2 s(-1) at 25 degrees C and there was no significant effect of alkyl chain length on the measured value of D.

Benzalkonium Compounds↗
PubMed2000

Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? A cautionary note based on compromised mucociliary transport.

BACKGROUND: Topical nasal solution and suspension delivery systems are available for short- and long-acting vasoconstrictors, ipratropium, cromolyn, azelastine, and glucocorticosteroids. The use of intranasal glucocorticosteroids has increased substantially because the efficacy of these agents has been well established for the treatment of perennial and seasonal allergic rhinitis. Adverse local effects of burning, irritation, and dryness are occasionally associated with glucocorticosteroid nasal preparations. Benzalkonium chloride (BKC) is a quaternary ammonium antimicrobial agent included in some nasal solutions (including glucocorticosteroids) to prevent the growth of bacteria. Some reports suggest that BKC in nasal sprays may cause adverse effects, including reduced mucociliary transport, rhinitis medicamentosa, and neutrophil dysfunction. OBJECTIVE: This article summarizes recent literature about possible adverse biologic effects associated with BKC as a nasal spray preservative by examining its effects on the following properties of mucociliary transport: ciliary motion, ciliary form, ciliary beat frequency, electron microscopy, and particle movement/saccharin clearance tests. CONCLUSION: Both animal and human in vitro data suggest that BKC promotes ciliostasis and reduction in mucociliary transport that may be partially masked by absorption and dilution effects occurring in respiratory mucus. These possible confounding factors may account for several disparate human in vivo results. The use of BKC-free glucocorticosteroid formulations should be considered, particularly in patients who complain of nasal burning, dryness, or irritation.

Animals↗
PubMed1999

Bronchoconstrictor additives in bronchodilator solutions.

Nebulized bronchodilator solutions are available in the United States as both nonsterile and sterile-filled products. Sulfites, benzalkonium chloride (BAC), or chlorobutanol are added to nonsterile products to prevent bacterial growth, but there have been reports of contaminated solutions containing preservatives. Ethylenediamine tetraacetic acid (EDTA) is added to some products to prevent discoloration of the solution. With the exception of chlorobutanol, all of these additives are capable of inducing bronchospasm in a concentration-dependent manner. However, it is rarely apparent to the patient or health care provider that the additive diminishes the bronchodilator effects. Older products (eg, isoproterenol and isoetharine) contain enough sulfites to produce bronchospasm in most patients with asthma, even in those without a prior history of sulfite sensitivity. Bronchoconstriction from inhaled BAC is cumulative, prolonged, and correlates directly with basal airway responsiveness. The multidose dropper bottle of albuterol contains 50 microg BAC/dose, which is below the threshold for bronchoconstriction whereas the screwcap unit-dose vial contains 300 microg/dose, which is above the threshold for many patients. If the screwcap product is used in the emergency department, a patient could receive as much as 1800 microg of BAC in the first hour. Three sterile-filled unit dose albuterol products contain no additives, whereas a fourth, (manufactured by Dey Laboratories) contains 300 microg of EDTA, which is also below the threshold dose for bronchoconstriction. Only additive-free sterile solutions should be used for hourly or continuous nebulization of albuterol. The multidose dropper bottle or the Dey product can be used when the interval between doses is longer, whereas the screwcap product should not be used for acute therapy. Ipratropium is available only as a sterile, additive-free unit-dose vial, as is levalbuterol.

Administration, Inhalation↗
PubMed1999

Adverse effects of benzalkonium chloride on the nasal mucosa: allergic rhinitis and rhinitis medicamentosa.

Prolonged, repeated use of nasal decongestants for symptomatic relief of allergic rhinitis often results in rhinitis medicamentosa (RM), a condition involving "rebound swelling" and additional congestion. Most decongestant sprays contain the preservative benzalkonium chloride (BKC), which causes toxic reactions in the nose, eyes, ears, and lungs, and may exacerbate the symptoms of allergic rhinitis. Recent studies demonstrate the effects of nasal sprays containing BKC or the decongestant oxymetazoline (OXY) in the development of RM. Using rhinostereometry, a technique that measures nasal mucosal swelling and nasal reactivity (with histamine challenge tests), prolonged use of OXY has been shown to induce nasal mucosal swelling and hyperreactivity. Sustained use of BKC alone induces nasal mucosal swelling and, in combination with OXY, BKC appears to have a long-term adverse effect on nasal mucosa. Its presence may also contribute to the RM resulting from overuse of decongestant sprays. Additional research is needed to confirm the deleterious effects of BKC in nasal products. However, these potential effects may be points of clinical differentiation in the treatment of allergic rhinitis and prevention of RM.

Benzalkonium Compounds↗
PubMed1992

Corneal epithelial permeability of dry eyes before and after treatment with artificial tears.

PURPOSE: The question of whether artificial tears can lead to objective improvement of ocular surface disease in dry eyes is still unanswered. The aim of the current study is to assess the influence of artificial tears on corneal epithelial permeability of dry eyes. Furthermore, the effect of benzalkonium chloride, used as a preservative of artificial tears, on corneal epithelial permeability is investigated. METHODS: The corneal epithelial permeability of 40 dry eye patients (80 eyes) was measured by computerized objective fluorophotometry before and 6 weeks after treatment with artificial tears containing either polyvinyl pyrrolidone 2% without preservative (20 patients) or polyvinyl pyrrolidone 2% preserved with benzalkonium chloride 0.005% (20 patients). RESULTS: Before treatment, the epithelial permeability of the dry eye patients was found to be 2.7 times that of a control group. After treatment, the epithelial permeability of patients treated with unpreserved polyvinyl pyrrolidone 2% had decreased significantly (-37%; P less than 0.001), whereas patients who had been treated with polyvinyl pyrrolidone 2% preserved with benzalkonium chloride 0.005% showed an increase in epithelial permeability (+21%; P = 0.05%). CONCLUSION: These data suggest that, in dry eyes, treatment with unpreserved artificial tears may lead to an objective improvement in corneal surface disease. However, this effect may be counteracted by preservation of tear substitutes with benzalkonium chloride.

Benzalkonium Compounds↗
PubMed1999

Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies.

OBJECTIVES: To investigate conjunctival and trabecular specimens from patients with glaucoma according to the duration and number of drugs received before filtration surgery, and to confirm, in a complementary experimental model, the role of preservative by comparing the effects of preserved and nonpreserved timolol. STUDY DESIGN: Experimental animal and human tissue study. PARTICIPANTS: Paired specimens of conjunctiva and trabeculum were taken from 61 patients undergoing trabeculectomy. Twenty-six patients were treated with 2 or more drugs for at least 1 year; 30 had received a beta-blocker for more than 1 year and 5 underwent primary surgery. A second study was performed in 25 rats receiving topical solutions in both eyes for 1 month. INTERVENTION: Immunohistochemistry was performed in all biopsy specimens using 12 different monoclonal antibodies. Ocular structures from rats treated for 1 month with preserved 0.5% timolol, nonpreserved 0.5% timolol, or 0.01% benzalkonium chloride were similarly investigated in an experimental study. MAIN OUTCOME MEASURES: Inflammatory cell infiltrates and fibroblasts were evaluated in biopsies, as well as in animal specimens, together with histologic changes induced by the drugs applied. RESULTS: Twenty-four of 26 conjunctivae and 21 of 24 trabecular pieces from multitreated patients were found to be abnormally infiltrated by cells expressing inflammatory or fibroblastic markers or both. Nineteen of 30 conjunctivae and 9 of 22 trabeculums in the monotherapy group and only 1 of 5 specimens from the primary surgery group were abnormal. In rats, preserved timolol and benzalkonium similarly showed infiltrates together with toxic histopathologic changes as compared to the nonpreserved timolol and control groups. CONCLUSIONS: These two combined studies confirmed histopathologic effects of antiglaucomatous drugs on the conjunctiva and showed similar effects in the trabecular meshwork. The experimental study showed that benzalkonium chloride is at least, to a large part, responsible for these toxic or immunoinflammatory effects or both on the ocular structures.

Administration, Topical↗
PubMed2002

Development of viral disinfectant assays for duck hepatitis B virus using cell culture/PCR.

Human hepatitis B virus (HBV) is a worldwide public health problem with chronic carriers at risk for developing cirrhosis and hepatocellular carcinoma. Accidental nosocomial infections from inadequately disinfected equipment or exposure to blood and body fluids from patients are major routes. To solve such problems, disinfectants to inactivate HBV must be validated. Duck hepatitis B virus (DHBV) is accepted as a surrogate for HBV, due to their similar sensitivities to disinfectants and its safety. Ducklings are used for disinfectant efficacy assays; however, the same virus titer is obtained using duck embryonic hepatocytes. Viral titration in disinfectant efficacy assay is conducted using Southern hybridization of infected duck serum. However, this test requires radioisotopes. Therefore, disinfectant assessment protocols were developed using duck embryonic hepatocytes with polymerase chain reaction (PCR) or nested PCR. The ease of handling, lowered cost and enhanced sensitivity make PCR desirable. Chicken embryonic hepatocytes were applied to DHBV disinfectant efficacy assay. Results were consistent and could be used under certain conditions. The virucidal activities of two quaternary ammonium chloride disinfectants, n-alkyl dimethyl benzyl ammonium chloride and alkyl dimethyl benzyl ammonium chloride (10C-12C) were compared and effective concentrations were 1200 and 1800 ppm, respectively. Efficacies of these disinfectants were validated using real-time quantitative PCR. Results confirmed that the efficacy of n-alkyl dimethyl benzyl ammonium chloride was higher than alkyl dimethyl benzyl ammonium chloride (10C-12C). This assay was useful for rapid discrimination of killing potentials of disinfectants. In conclusion, these assays can be applied to other viruses that are unable to cause CPE in cell cultures and broadened the utility of DHBV as animal model for HBV.

Animals↗
PubMed2001

Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies.

Serum amyloid P component (SAP) binds in vitro Ca(2+)-dependently to several ligands including oligosaccharides with terminal mannose and galactose. We have earlier reported that SAP binds to human influenza A virus strains, inhibiting hemagglutinin (HA) activity and virus infectivity in vitro. These studies were extended to comprise five mouse-adapted influenza A strains, two swine influenza A strains, a mink influenza A virus, a ferret influenza A reassortant virus, a influenza B virus and a parainfluenza 3 virus. The HA activity of all these viruses was inhibited by SAP. Western blotting showed that SAP bound to HA trimers, monomers and HA1 and HA2 subunits of influenza A virus. Binding studies indicated that galactose, mannose and fucose moieties contributed to the SAP reacting site(s). Intranasal administration of human SAP to mice induced no demonstrable toxic reactions, and circulating antibodies against SAP were not detected. Preincubation of virus (A/Japan/57) with SAP prevented primary infection of mice and development of antiviral antibodies. After a single intranasal administration of SAP (40 microg) 1 h before primary infection with virus (2LD(50)), nine out of 10 mice survived on day 10 and these mice approached normal body weight, whereas control mice (one out of five surviving on day 10) died. The data provide evidence of the potential of intranasally administered SAP for prophylactic treatment of influenza A virus infections in humans.

Animals↗