Christine Moresoli

In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials

The in vitro uptake and release behaviour of cromolyn sodium, ketotifen fumarate, ketorolac tromethamine and dexamethasone sodium phosphate with silicon-containing (lotrafilcon and balafilcon) and p-HEMA-containing (etafilcon, alphafilcon, polymacon, vifilcon and omafilcon) hydrogel contact lenses indicated that both drug and material affected the uptake and release behaviour. Rapid uptake and release (within 50 min) was observed for all drugs except ketotifen fumarate which was more gradual taking approximately 5h. Furthermore, the maximum uptake differed significantly between drugs and materials. The highest average uptake (7879+/-684 microg/lens) was cromolyn sodium and the lowest average uptake (67+/-13 microg/lens) was dexamethasone sodium phosphate. Partial release of the drug taken up was observed for all drugs except dexamethasone sodium phosphate where no release was detected. Sustained release was demonstrated only by ketotifen fumarate. Drug uptake/release appeared to be a function of lens material ionicity, water and silicon content. The silicon-containing materials released less drug than the p-HEMA-containing materials. The lotrafilcon material demonstrated less interactions with the drugs than the balafilcon material which can be explained by their different bulk composition and surface treatment.

Identifying fouling events in a membrane-based drinking water treatment process using principal component analysis of fluorescence excitation-emission matrices

The identification of key foulants and the provision of early warning of high fouling events for drinking water treatment membrane processes is crucial for the development of effective countermeasures to membrane fouling, such as pretreatment. Principal foulants include organic, colloidal and particulate matter present in the membrane feed water. In this research, principal component analysis (PCA) of fluorescence excitation-emission matrices (EEMs) was identified as a viable tool for monitoring the performance of pre-treatment stages (in this case biological filtration), as well as ultrafiltration (UF) and nanofiltration (NF) membrane systems. In addition, fluorescence EEM-based principal component (PC) score plots, generated using the fluorescence EEMs obtained after just 1hour of UF or NF operation, could be related to high fouling events likely caused by elevated levels of particulate/colloid-like material in the biofilter effluents. The fluorescence EEM-based PCA approach presented here is sensitive enough to be used at low organic carbon levels and has potential as an early detection method to identify high fouling events, allowing appropriate operational countermeasures to be taken.

Reversible and irreversible low-pressure membrane foulants in drinking water treatment: Identification by principal component analysis of fluorescence EEM and mitigation by biofiltration pretreatment

With the increased use of membranes in drinking water treatment, fouling--particularly the hydraulically irreversible type--remains the main operating issue that hinders performance and increases operational costs. The main challenge in assessing fouling potential of feed water is to accurately detect and quantify feed water constituents responsible for membrane fouling. Utilizing fluorescence excitation-emission matrices (EEM), protein-like substances, humic and fulvic acids, and particulate/colloidal matter can be detected with high sensitivity in surface waters. The application of principal component analysis to fluorescence EEMs allowed estimation of the impact of surface water constituents on reversible and irreversible membrane fouling. This technique was applied to experimental data from a two year bench-scale study that included thirteen experiments investigating the fouling potential of Grand River water (Ontario, Canada) and the effect of biofiltration pre-treatment on the level of foulants during ultrafiltration (UF). Results showed that, although the content of protein-like substances in this membrane feed water (=biofiltered natural water) was much lower than commonly found in wastewater applications, the content of protein-like substances was still highly correlated with irreversible fouling of the UF membrane. In addition, there is evidence that protein-like substances and particulate/colloidal matter formed a combined fouling layer, which contributed to both reversible and irreversible fouling. It is suggested that fouling transitions from a reversible to an irreversible regime depending on feed composition and operating time. Direct biofiltration without prior coagulant addition reduced the protein-like content of the membrane feed water which in turn reduced the irreversible fouling potential for UF membranes. Biofilters also decreased reversible fouling, and for both types of fouling higher biofilter contact times were beneficial.

Assessing the role of feed water constituents in irreversible membrane fouling of pilot-scale ultrafiltration drinking water treatment systems.

Fluorescence excitation-emission matrix (EEM) approach together with principal component analysis (PCA) was used for assessing hydraulically irreversible fouling of three pilot-scale ultrafiltration (UF) systems containing full-scale and bench-scale hollow fiber membrane modules in drinking water treatment. These systems were operated for at least three months with extensive cycles of permeation, combination of back-pulsing and scouring and chemical cleaning. The principal component (PC) scores generated from the PCA of the fluorescence EEMs were found to be related to humic substances (HS), protein-like and colloidal/particulate matter content. PC scores of HS- and protein-like matter of the UF feed water, when considered separately, showed reasonably good correlations with the rate of hydraulically irreversible fouling for long-term UF operations. In contrast, comparatively weaker correlations for PC scores of colloidal/particulate matter and the rate of hydraulically irreversible fouling were obtained for all UF systems. Since, individual correlations could not fully explain the evolution of the rate of irreversible fouling, multi-linear regression models were developed to relate the combined effect of HS-like, protein-like and colloidal/particulate matter PC scores to the rate of hydraulically irreversible fouling for each specific UF system. These multi-linear regression models revealed significant individual and combined contribution of HS- and protein-like matter to the rate of hydraulically irreversible fouling, with protein-like matter generally showing the greatest contribution. The contribution of colloidal/particulate matter to the rate of hydraulically irreversible fouling was not as significant. The addition of polyaluminum chloride, as coagulant, to UF feed appeared to have a positive impact in reducing hydraulically irreversible fouling by these constituents. The proposed approach has applications in quantifying the individual and synergistic contribution of major natural water constituents to the rate of hydraulically irreversible membrane fouling and shows potential for controlling UF irreversible fouling in the production of drinking water.

Modeling flux behavior for membrane filtration of apple juice

The flux behavior of ceramic membranes with different pore sizes (0.2, 0.1 and 0.02 μm) was examined during dead-end membrane filtration of depectinized control (CTJ) and ascorbic acid treated (AAJ) apple juices. A new model based on an expanded exponential relationship was developed. The model represented the flux with precision over the entire filtration process for both juice types and all membrane pore sizes. Two parameters, A and B, provided a measure of the rate of flux decline. The same approach was used to model the permeate flux of CTJ for various 0.2 μm pore size polymeric membrane materials operated in a dead-end mode, and for tubular ultrafiltration membranes of different pore sizes (9, 20 and 100 kDa) operated in crossflow mode.

Ciprofloxacin interaction with silicon-based and conventional hydrogel contact lenses

Purpose. Hydrogel contact lenses can be used as bandage lenses to protect the corneal surface after injury. The use of novel silicon-based hydrogel lens materials as bandage lenses has not gained widespread acceptance. As a first step toward advocating their usefulness as bandage lenses, their interaction with ocular pharmaceuticals must be understood because topical agents are often administered in conjunction with bandage lenses. Methods. The in vitro uptake and release of ciprofloxacin from silicone-based hydrogel (SH) and conventional pHEMA-based (CH) hydrogel contact lenses was examined by spectrophotometric evaluation of the drug concentration in saline solution. Results. The hydrogel contact lenses tested showed similar drug uptake (average 1800 &mgr;g/lens) but different levels of drug release. Multiphoton laser microscopy indicated that ciprofloxacin was distributed throughout the lens thickness, with higher levels of drug at the surface owing to drug precipitation. The drug adsorption onto the lenses was partially reversible. The SH lenses released a lower amount of drug than CH lenses (72 vs. 168 &mgr;g/lens). Ionic lenses released less drug than non-ionic lenses (127 vs. 151 &mgr;g/lens). Conclusions. The differences in ciprofloxacin uptake and release between SH and CH materials may not be clinically significant because the amount of drug released from all lenses would be above the MIC90 of ciprofloxacin for common ocular pathogens. These results indicate that material properties have a significant impact on drug-lens interactions.

Calcium Interacts with Antifreeze Proteins and Chitinase from Cold-Acclimated Winter Rye

During cold acclimation, winter rye (Secale cereale) plants accumulate pathogenesis-related proteins that are also antifreeze proteins (AFPs) because they adsorb onto ice and inhibit its growth. Although they promote winter survival in planta, these dual-function AFPs proteins lose activity when stored at subzero temperatures in vitro, so we examined their stability in solutions containing CaCl2, MgCl2, or NaCl. Antifreeze activity was unaffected by salts before freezing, but decreased after freezing and thawing in CaCl2 and was recovered by adding a chelator. Ca2+ enhanced chitinase activity 3- to 5-fold in unfrozen samples, although hydrolytic activity also decreased after freezing and thawing in CaCl2. Native PAGE, circular dichroism, and Trp fluorescence experiments showed that the AFPs partially unfold after freezing and thawing, but they fold more compactly or aggregate in CaCl2. Ruthenium red, which binds to Ca2+-binding sites, readily stained AFPs in the absence of Ca2+, but less stain was visible after freezing and thawing AFPs in CaCl2. We conclude that the structure of AFPs changes during freezing and thawing, creating new Ca2+-binding sites. Once Ca2+ binds to those sites, antifreeze activity, chitinase activity and ruthenium red binding are all inhibited. Because free Ca2+ concentrations are typically low in the apoplast, antifreeze activity is probably stable to freezing and thawing in planta. Ca2+ may regulate chitinase activity if concentrations are increased locally by release from pectin or interaction with Ca2+-binding proteins. Furthermore, antifreeze activity can be easily maintained in vitro by including a chelator during frozen storage.

Survey of bandage lens use in North America, October-December 2002.

Purpose. The purpose of this work was to report the findings of a survey of current modes of bandage lens (BL) use by optometrists and ophthalmologists in Canada and the United States in 2002. Methods. Two thousand voluntary surveys were sent to ophthalmic practitioners across the United States and Canada. The survey contained a questionnaire with 15 questions about the practitioner’s background and BL-prescribing trends and views. It also contained a 10-patient list with parameters such as patient profile, BL type, and pharmaceutical use. Results. Seventy-two percent of those opthalmic practitioners who returned surveys have prescribed soft contact lenses for therapeutic purposes. BLs are most often used for corneal wound healing and for managing postoperative complications. Pharmaceuticals are concomitantly administered in more than 81% of the patients treated with BLs. The most commonly prescribed pharmaceuticals are antibiotics (47.5% of patients) and antiinflammatory drugs (42% of patients). ACUVUE and Focus Night & Day lenses are the most popular choices for BLs. Most respondents (93%), regardless of whether they routinely prescribed BLs, would be interested in a BL that could deliver a topical pharmaceutical drug. Conclusions. The results from the survey indicated that BL use is prevalent across North America. The BL-prescribing habits of North American practitioners indicate that there is a strong interest and need for a drug-delivering therapeutic soft contact lens.

Acquiring reproducible fluorescence spectra of dissolved organic matter at very low concentrations

A method that would allow for fast and reliable measurements of dissolved organic matter (DOM), both at low and high concentration levels would be a valuable tool for online monitoring of DOM. This could have applications in a variety of areas including membrane treatment systems for drinking water applications which is of interest to our group. In this study, the feasibility of using fluorescence spectroscopy for monitoring DOM at very low concentration levels was demonstrated with an emphasis on optimizing the instrument parameters necessary to obtain reproducible fluorescence signals. Signals were acquired using a cuvette or a fibre optic probe assembly, the latter which may have applications for on-line or in-line monitoring. The instrument parameters such as photomultiplier tube (PMT) voltage, scanning rate and slit width were studied in detail to find the optimum parameter settings required. The results showed that larger excitation and emission slit widths were preferred, over larger PMT voltage or lower scanning rates, to obtain reproducible and rapid measurements when measuring very low concentration levels of DOM. However, this approach should be implemented with caution to avoid any reduction of the signal resolution.

Experimental verification of the shear-induced hydrodynamic diffusion model of crossflow microfiltration, with consideration of the transmembrane pressure axial variation

Abstract A model based on the shear-induced hydrodynamic diffusion theory, with the consideration of the axial variation of the transmembrane pressure drop, was developed for a hollow fiber crossflow microfiltration module. The model predictions agreed closely with experimental data obtained for a commercial hollow fiber microfiltration module used for a monodisperse latex particle suspension forming a stagnant particle layer at the membrane surface. The pressure drop across the stagnant particle layer and the membrane, the permeate flux and the stagnant particle layer profile predicted by the proposed model were compared with the predictions of the previous model of Romero and Davis, adapted for an hollow-fiber geometry and of the previous model of Zydney and Colton. The results indicated that the proposed model could predict a decrease in the stagnant particle layer thickness at the exit of the fiber that has been observed experimentally.