Application Of Polyethylene Glycol Research Articles

PEGylation in Pharmaceutical Development: Current Status and Emerging Trends in Macromolecular and Immunotherapeutic Drugs.

The purpose of the research is to examine the advantages and difficulties of target-site drug delivery methods, with an emphasis on the application of polyethylene glycol (PEG) to enhance drug solubility, bioavailability, and immune response characteristics. It has been demonstrated that this method lowers immunogenicity, enhances pharmacokinetics, and helps drugs pass the blood-brain barrier while reducing reticuloendothelial system clearance. PEG and its derivatives are being used more and more to alter therapeutic substances, offering an escape from some of the drawbacks of conventional medication formulations. In the review, different PEGylation tactics are examined, including cutting-edge methods for reversing multi-drug resistance in nanocarriers. PEGylation has a number of benefits, but there are still drawbacks, including the immunogenic reaction to PEG, which is sometimes referred to as "anti-PEG antibodies," and stability problems that call for the creation of countermeasures. The study devotes a large amount of its space to listing FDA-approved PEGylated medications, emphasizing their therapeutic advantages and clinical uses in a range of medical specialties. The research also explores the regulatory environment that surrounds PEG, closely examining its effectiveness and safety in medication compositions. The review goes beyond PEGylation and includes lipid-based nanocarriers, including liposomes, nanostructured lipid carriers (NLCs), and solid lipid nanoparticles (SLNs). Because these nanocarriers can target specific tissues or cells, improve bioavailability, and encapsulate pharmaceuticals, they are becoming more and more significant in drug delivery systems. The Target Product Profile (TPP) and Quality by Design (QbD) principles serve as the foundation for the creation and characterization of these lipid-based systems. These tools direct the methodical assessment of material properties and risk assessments during the formulation phase. This method guarantees that the finished product satisfies the appropriate requirements for efficacy, safety, and quality. The regulatory status and safety profile of nano lipid carriers are covered in the paper's conclusion, which emphasizes the importance of careful examination and oversight in bringing these cutting-edge products to market. Overall, this thorough analysis highlights the revolutionary potential of lipid-based nanocarriers and PEGylation in improving drug delivery and therapeutic efficacy, but it also draws attention to the continued difficulties and legal issues that need to be resolved in order to fully reap the benefits of these technologies in biomedicine.

Evaluation of the Effectiveness of Patient’s Position Change during the Withdrawal Phase of Colonoscopy from Left Lateral Decubitus to Supine Position on Increasing Adenoma Detection Rate: A Randomized Controlled Trial

Background: Improvement in adenoma detection rate (ADR) reduces colorectal cancer incidence by increasing the colonoscopy quality. Using dynamic patient position changes during the withdrawal phase has shown promise in increasing ADR. We conducted this study to assess the effectiveness of the supine position on the improvement of ADR to improve its feasibility and avoid frequent patient position changes, particularly in sedated patients. Methods: This was a randomized, single-blind, parallel-group, single-center study implemented in the Mehregan private in Babol. Inclusion criteria were 40 to 85 years old, 4 L application of polyethylene glycol from the day before the procedure, no history of inflammatory bowel disease, bowel surgery, musculoskeletal problems, and negative familial history of colorectal cancer. Patients were allocated in a 1:1 ratio to the supine or left lateral positions during the withdrawal phase. All colonoscopies were performed by a single physician using a Fujifilm colonoscope. A P-value of <0.005 was considered statistically significant. Results: A total of 880 patients were assessed for eligibility, of which 472 patients were included in the final analysis; 53.4% were female, the mean age of participants was 55.86±10.30 years old, 95.1% of patients had adequate bowel preparation, and adenomatous polyps were the most common histopathologic type (63.7%). Despite the intervention group’s higher rate of ADR and PDR (19.5% vs. 17.7% for ADR and 27.2% vs. 26.5% for PDR), no statistically significant difference in ADR or PDR was detected (P=0.613 and 0.866, respectively). Conclusion: No statistical significance was observed despite the increase in ADR when the supine position was used exclusively during the withdrawal phase. As a result, we recommend that the dynamic position change method be used if a position change is required. Nonetheless, additional research is required to determine a more effective alternative to dynamic position change in obese or heavily sedated patients.

Preparation of hydrophobic shaped core–shell phase change pellets and thermoregulation effect in buildings

The application of Polyethylene glycol (PEG)-based form-stable phase change materials (FSPCMs) in construction engineering is limited by two problems: poor water resistance and weak interface interaction with building materials. To solve these problems, in this study, a shell material (named SSHS FSPCM) with phase change functionality and hydrophobic properties was innovatively proposed for the encapsulation of PEG-based FSPCMs and was prepared using the melt blending method. Differential scanning calorimetry and X-ray diffractometry verified that SSHS FSPCM has a large storage enthalpy of up to 143.0 J/g and excellent crystallisation properties. More significantly, phase change pellets with superhydrophobic properties (contact angle of 167 °) were prepared for the first time, inspired by the core–shell structure and the bionic lotus leaf structure. Meanwhile, the hydrophobic nano-SiO2 on the surface of the phase change pellets can increase the interfacial shear strength between SSHS FSPCM and inorganic building materials by 225 %. Furthermore, the building thermoregulation test showed that phase change pellets can not only regulate the indoor temperature of building (by 9 °C during the heating phase) but also significantly control the temperature of that building, providing opportunities for its practical engineering application.

Rapid osmotic adjustment in leaf elongation zone during polyethylene glycol application: Evaluation of the imbalance between assimilation and utilization of carbohydrates

Rapid osmotic adjustment in leaf elongation zone during polyethylene glycol application: Evaluation of the imbalance between assimilation and utilization of carbohydrates

Rapid osmotic adjustment in leaf elongation zone during polyethylene glycol application: Evaluation of the imbalance between assimilation and utilization of carbohydrates

Rapid osmotic adjustment in leaf elongation zone during polyethylene glycol application: Evaluation of the imbalance between assimilation and utilization of carbohydrates

Overexpression of the potato StEPF2 gene confers enhanced drought tolerance in Arabidopsis

Epidermal patterning factor 2 (EPF2) is a negative regulator of stomatal development, and is essential for plant growth, development, and environmental stress responses. However, the role of EPF2 in potato (Solanum tuberosum) has not been investigated to date. Here, we cloned and characterized the potato EPF2-like gene (StEPF2). StEPF2 is predominantly intercellular space localized and its transcripts were rhythmically expressed, and showed the highest expression in apical unexpanded leaves. Expression of StEPF2 was markedly down-regulated in response to abscisic acid and sodium chloride treatments; however, upon the application of polyethylene glycol, the expression of StEPF2 peaked at 4 h and then decreased gradually. Overexpression of StEPF2 in Arabidopsis (OE) substantially reduced stomatal density and photosynthetic rate, but had little effects on plant growth. Under drought stress, OE lines maintained higher photosynthetic rates, photosystem II efficiency, and instantaneous water use efficiency than wild-type (WT) plants. Moreover, OE lines showed less water loss and hydrogen peroxide accumulation in detached leaves compared with WT plants. Thus, our results suggest that StEPF2 acts as a negative regulator of stomatal development in potato, indicating that the role of EPF2 is conserved across plant species. Overall, StEPF2 represents an important target for the development of drought-tolerant potato cultivars via genetic engineering.

Theranostics Based on Liposome: Looking Back and Forward.

Liposome is one of the oldest yet most successful nanomedicine platforms. Doxil®, PEGylated liposome loaded with doxorubicin (DOX), was approved by the FDA in 1995 for the treatment of AIDS-related Kaposi's sarcoma, and it was the first approval for nanomedicine. Since then, liposome-based therapeutics were approved for the treatment of various diseases and many clinical trials are underway. The success of the liposome-based therapeutics was due to following factors: (1) ease of synthesis, (2) biocompatibility, (3) the ability to load both hydrophilic and hydrophobic agents, and (4) long circulation property after application of polyethylene glycol (PEG). Recently, more functionalities are introduced to liposome platform, which are (1) in vivo imaging probes for optical, magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), (2) pH and temperature-sensitive lipid moiety, and (3) novel agents for photodynamic and photothermal therapies (PDT, PTT). These conventional and newly tested advantages make the liposome to be one of the most promising nanoplatforms for theranostics.

Study of print paste composition for natural and synthetic textiles. Part 1: Printing of cellulosic fabrics

Reactive dyes have proven to be one of the most commonly applied classes of modern synthetic dyes. Unlike other dye classes for cellulosic textiles dyeing and printing, the reactive dyes provide excellent wash-fastness for a very wide shade gamut. One of the most important components of print paste, especially for reactive dye printing of cellulosic textiles, is urea. Despite urea’s great importance in adjustment of dye distribution in the paste, it can cause environmental problems. In this study, the application of polyethylene glycol (PEG) (10, 30 and 50 g/100 g) was examined for urea’s replacement in reactive dye print paste. The optimal concentration of sodium bicarbonate, as pH buffer, was found. Testing results of colour fastness and colour measurements approved PEG application possibility.

Physicochemical characterization of PEG-modified PbO2 coatings electrodeposited from a methanesulfonate bath

This study explores the preparation and application of polyethylene glycol (PEG)-modified PbO2 electrodes. The PEG-modified PbO2 coatings were electrodeposited on a Ti/SnO2-Sb substrate from a methanesulfonate electrolytic bath containing different amounts of PEG. Structural and morphologic characterization was carried out for the deposited electrodes. The presence of PEG in the deposition bath represses the nucleation process and grain growth process in PbO2 deposition. Increasing PEG addition results in an increased [Formula: see text]-PbO2 content and decreased crystallite size. At a limited PEG addition [Formula: see text]4 g/L, a rough and pyramidal surface morphology is presented in the PbO2 coatings. A higher PEG addition at 6 g/L leads to a dense and smooth coating surface yet with less uniformity. Electrochemical characterization reveals a great electrocatalytic activity for the modified PbO2 electrodes when the PEG addition is [Formula: see text]4 g/L.

Functional and Anatomical Outcomes of Facial Nerve Injury With Application of Polyethylene Glycol in a Rat Model.

Functional and anatomical outcomes after surgical repair of facial nerve injury may be improved with the addition of polyethylene glycol (PEG) to direct suture neurorrhaphy. The application of PEG has shown promise in treating spinal nerve injuries, but its efficacy has not been evaluated in treatment of cranial nerve injuries. To determine whether PEG in addition to neurorrhaphy can improve functional outcomes and synkinesis after facial nerve injury. In this animal experiment, 36 rats underwent right facial nerve transection and neurorrhaphy with addition of PEG. Weekly behavioral scoring was done for 10 rats for 6 weeks and 14 rats for 16 weeks after the operations. In the 16-week study, the buccal branches were labeled and tissue analysis was performed. In the 6-week study, the mandibular and buccal branches were labeled and tissue analysis was performed. Histologic analysis was performed for 10 rats in a 1-week study to assess the association of PEG with axonal continuity and Wallerian degeneration. Six rats served as the uninjured control group. Data were collected from February 8, 2016, through July 10, 2017. Polyethylene glycol applied to the facial nerve after neurorrhaphy. Functional recovery was assessed weekly for the 16- and 6-week studies, as well as motoneuron survival, amount of regrowth, specificity of regrowth, and aberrant branching. Short-term effects of PEG were assessed in the 1-week study. Among the 40 male rats included in the study, PEG addition to neurorrhaphy showed no functional benefit in eye blink reflex (mean [SEM], 3.57 [0.88] weeks; 95% CI, -2.8 to 1.9 weeks; P = .70) or whisking function (mean [SEM], 4.00 [0.72] weeks; 95% CI, -3.6 to 2.4 weeks; P = .69) compared with suturing alone at 16 weeks. Motoneuron survival was not changed by PEG in the 16-week (mean, 132.1 motoneurons per tissue section; 95% CI, -21.0 to 8.4; P = .13) or 6-week (mean, 131.1 motoneurons per tissue section; 95% CI, -11.0 to 10.0; P = .06) studies. Compared with controls, neither surgical group showed differences in buccal branch regrowth at 16 (36.9 motoneurons per tissue section; 95% CI, -14.5 to 22.0; P = .28) or 6 (36.7 motoneurons per tissue section; 95% CI, -7.8 to 18.5; P = .48) weeks or in the mandibular branch at 6 weeks (25.2 motoneurons per tissue section; 95% CI, -14.5 to 15.5; P = .99). Addition of PEG had no advantage in regrowth specificity compared with suturing alone at 16 weeks (15.3% buccal branch motoneurons with misguided projections; 95% CI, -7.2% to 11.0%; P = .84). After 6 weeks, the number of motoneurons with misguided projections to the mandibular branch showed no advantage of PEG treatment compared with suturing alone (12.1% buccal branch motoneurons with misguided projections; 95% CI, -8.2% to 9.2%; P = .98). In the 1-week study, improved axonal continuity and muscular innervation were not observed in PEG-treated rats. Although PEG has shown efficacy in treating other nervous system injuries, PEG in addition to neurorraphy was not beneficial in a rat model of facial nerve injury. The addition of PEG to suturing may not be warranted in the surgical repair of facial nerve injury. NA.

Green solvents in organoselenium chemistry

Organoselenium chemistry involves unique methods for the preparation of reaction intermediates and biologically relevant compounds. However, common methods frequently have drawbacks such as the use of halogenated volatile solvents, expensive catalysts systems and sophisticated experimental fittings. Therefore, sustainable organoselenium chemistry is developing. Here, we review green solvent alternatives in organoselenium chemistry. We present the application of the ionic liquids and deep eutectic solvents in the synthesis of seleno-functionalized molecules under mild reaction conditions; the application of polyethylene glycol, glycerol and ethanol as solvents; and the use of organoselenium compounds as starting materials for the preparation of ionic liquids.

High Light Acclimated Developing Primary Leaves of Wheat Seedlings Generate Signal for Stress Adaptation through Super Oxide Dismutase

Wheat seedlings grown in petri dishes were acclimated to high light during their development and subsequently were subjected to osmotic stress by application of polyethylene glycol (PEG). The photochemical efficiency of photosystem II (PS II) of the acclimated seedlings was found to be higher than that of non-acclimated ones under osmotic stress during senescence. The damage of the photosynthetic apparatus seems to be mediated by reactive oxygen species. The higher level of lutein (Lut) and superoxide dismutase (SOD) activity in acclimated seedlings suggest their involvement in the protective mechanism. The senescing leaves, although in a deteriorating phase, exhibit tolerance to osmotic stress due to the adaptation potential acquired earlier during high light (HL) acclimation.

Nonaqueous Biphasic Hydroformylation of Long Chain Alkenes Catalyzed by Water Soluble Phosphine Rhodium Catalyst with Polyethylene Glycol Instead of Water

The application of polyethylene glycol (donated as PEG), as an environmentally benign solvent instead of water, in rhodium catalyzed hydroformylation of long chain alkenes by using water soluble phosphine BISBIS or TPPTS (TPPTS: sodium salt of sulfonated triphenylphosphine, BISBIS: sodium salt of sulfonated 2,2′-bis(diphenylphosphinomethyl)-1,1′-biphenyl) is herein reported. The conversion of long chain alkenes in PEG-200 could reach above 95.0% after a short reaction time (15 min). In addition, an efficient phase separation and recycling of PEG-200 and catalyst were achieved. The leaching of rhodium into product phase detected by ICP-AES was less than 0.06 wt% of the initial amount.

Versatility of polyethylene glycol (PEG) in designing solid–solid phase change materials (PCMs) for thermal management and their application to innovative technologies

A review focussed on the preparation methods and applications of polyethylene glycol (PEG) based solid–solid phase change materials (PCMs).

Gene transcription and steviol glycoside accumulation in Stevia rebaudiana under polyethylene glycol-induced drought stress in greenhouse cultivation.

Stevia rebaudiana is a sweet herb of the Astraceae family, which is cultivated for the natural sweeteners it contains. The aim of this study was to assess the effect of drought, simulated by the application of polyethylene glycol (5%, 10%, and 15% w/v), on the content of steviol glycosides (SVglys) and transcription levels of six genes involved in the biosynthesis of these natural sweeteners. The transcription levels of ent‐kaurene synthase, ent‐kaurene oxidase, ent‐kaurenoic acid hydroxylase, and three UDP‐dependent glycosyltransferases, UGT85C2,UGT74G1 and UGT76G1 were downregulated under polyethylene glycol treatment. Polyethylene glycol treatment significantly decreased the amount of stevioside, rebaudioside A, B, C and F, steviolbioside, dulcoside A, rubusoside, and total SVglys. These results strongly suggest a close relationship of SVglys content with the transcription of genes involved in the SVglys biosynthesis pathway. Comparing the observations of the present study with other reports provided the knowledge that the Stevia response to drought stress can be influenced by different environmental and experimental factors, in addition to intensity of drought stress. In conclusion, these results strongly suggest that polyethylene glycol‐induced drought stress has a negative effect on the content of SVglys and transcription of SVglys biosynthetic genes and that this should be investigated further. We recommend that sufficient irrigation of Stevia is required to obtain a high content of SVglys.

Isolation and purification of Echinococcus granulosus antigen B from hydatid cyst fluid using three different methods.

Hydatid cyst, the larval stage of cestodes Echinococcus spp., is recognized as a zoonotic infection in the world. The World Health Organization (WHO) has recently classified echinococcosis in a group of neglected tropical diseases. The prevalence of Echinococcus granulosus infection is high in Iran due to the presence of various intermediate hosts in this country. Considering the rising trend of this zoonotic parasitic disease based on national epidemiological studies, diagnosis is of great significance. WHO has suggested the use of specific antigens, especially antigen B (AgB) for serological diagnostic tests. In general, AgB is a polymeric lipoprotein, which disintegrates into 8.12, 16, and 20.24 kDa subunits. In the present study, we applied three different methods for AgB isolation from hydatid cyst fluid (HCF) and compared their efficacy in AgB isolation. Finally, the protein concentration of this antigen was measured by Bradford assay and confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results showed that the application of polyethylene glycol (PEG 4000) as a thickener agent beside purification of HCF in dialysis bag and filtering and also dialysis against acetate buffer leading to the best quantity in purified antigen B.

Norway spruce embryogenesis: changes in carbohydrate profile, structural development and response to polyethylene glycol.

Two unrelated, geographically distinct, highly embryogenic lines of Norway spruce (Picea abies (L.) Karst.) were analysed to identify metabolic traits characteristic for lines with good yields of high-quality embryos. The results were compared with corresponding characteristics of a poorly productive line (low embryo yield, scarce high-quality embryos). The following carbohydrate profiles and spectra during maturation, desiccation and germination were identified as promising characteristics for line evaluation: a gradual decrease in total soluble carbohydrates with an increasing sucrose : hexose ratio during maturation; accumulation of raffinose family oligosaccharides resulting from desiccation and their rapid degradation at the start of germination; and a decrease in sucrose, increase in hexoses and the appearance of pinitol with proceeding germination. We propose that any deviation from this profile in an embryonic line is a symptom of inferior somatic embryo development. We further propose that a fatty acid spectrum dominated by linoleic acid (18 : 2) was a common feature of healthy spruce somatic embryos, although it was quite different from zygotic embryos mainly containing oleic acid (18 : 1). The responses of the lines to osmotic stress were evaluated based on comparison of control (without osmoticum) and polyethylene glycol (PEG)-exposed (PEG 4000) variants. Although genetically distinct, both highly embryogenic lines responded in a very similar manner, with the only difference being sensitivity to high concentrations of PEG. At an optimum PEG concentration (3.75 and 5%), which was line specific, negative effects of PEG on embryo germination were compensated for by a higher maturation efficiency so that the application of PEG at an appropriate concentration improved the yield of healthy germinants per gram of initial embryonal mass and accelerated the process. Polyethylene glycol application, however, resulted in no improvement of the poorly productive line.

Application of polyethylene glycol, cetrimide, chitosan and their mixtures on cotton muslin fabric to improve rot resistance, antimicrobial property and its salt-free reactive dyeing

In the present work, cotton muslin fabric is treated with eco-friendly antimicrobial agents in order to observe the effect of those chemicals on the rot resistance properties, physical appearance, important textile-related mechanical properties and dyeability with reactive dyes. The cotton fabric has been treated with polyethylene glycol (PEG 200), cetrimide and chitosan individually and their blends, in the presence of citric acid and sodium hydrogen phosphate as mixed catalyst to investigate the effect of such treatment on fabric properties of treated cotton mentioned above. Amongst all individual and combined applications of above said chemicals, it is observed that treatment with a mixture of chitosan and PEG is showing good result in terms of improvement in rot resistance performance and an optimum balance in other textile-related mechanical and appearance properties indicating lowest degradation against microbial attack. A series of experiments were undertaken with varying percentage of both the chemicals to arrive at the optimum ratio of mixture of PEG and chitosan and compared with such effect for treatment with conventional quaternary ammonium compound EPTAC. This treatment shows much balance results and also creates a newer provision of salt-free reactive dyeing of such treated/cationized cotton muslin fabric by unconventional reactive dyeing in acid bath after such chemical treatment/modifications.

Application of polyethyleneglycol (PEG) functionalized ionic liquids for the rhodium-catalyzed hydrosilylation reaction of alkenes

Rh(PPh3)3Cl–polyethyleneglycol (PEG) functionalized ionic liquids with various anions were used as a catalytic system for the hydrosilylation reaction of alkenes. The influence of the anion of the ionic liquid has been investigated. It was found that the anion has an impact on the catalytic activity and selectivity. [PEG400DIL][PF6]-[Rh(PPh3)3Cl] shows an improved catalytic performance towards the hydrosilylation reaction of alkenes. The scope of alkenes and recycling of the catalytic system have been investigated.

Neutralization of polyethylene glycol on ocular surface toxicity induced by benzalkonium chloride-preserved latanoprost

Background Reducing ocular surface toxicity induced by topical antiglaucoma medications,and thus improving the therapeutic compliance of glaucomatous patients to treating drug become an urgent issue in the long-term antiglaucomatous therapies.Whether polyethylene glycol,a new type of artificial tear,can play a protective role from ocular surface toxicity induced by topical antiglaucoma medications remains further study.Objective The present study was to investigate the protective effect of polyethylene glycol on ocular surface toxicity induced by prolonged use of benzalkonium chloride-preserved latanoprost eye drops.Methods Thirty adult female New Zealand rabbits were randomly divided into normal control group,phosphate buffer solution (PBS) group and polyethylene glycol eye drops group.PBS with 0.005％ latanoprost was topically administered for consequent 60 days in the PBS group,and 0.005％ latanoprost with polyethylene glycol eye drops was used at the same way in the polyethylene glycol group.Schirmer Ⅰ test,fluorescein and rose bengal staining of cornea and conjunctiva,conjunctiva impression cytology specimens collecting were performed before experiment as well as 31 and 61 days after administration of drug.Histomorphological and ultrastructural changes of cornea and conjunctiva were observed under the light microscopy,scanning and transmission electron microscopy on day 61.Results The score of corneal fluorescine staining was significantly different among the control group,PBS group and polyethylene glycol group (H =25.265,P＜0.001 ;H=29.426,P＜0.001) on day 31 and day 61.Significant difference also was found in the score of rose bengal staining of cornea and conjunctiva (H=26.167,P＜0.001 ;H =29.212,P＜0.001),Schirmer Ⅰ test value (F=4.746,P＜0.05) and conjunctival goblet cell density (F=18.055,P＜0.001).Compared with the control group,corneal fluorescein scores [0(0,1.0) vs.3 (2.0,3.0)] and rose bengal scores [0(0,1) vs.2(2,3)] were significantly increased (both P＜0.001),and Schirmer Ⅰ test value scores and conjunctival goblet cell density were decreased ((5.18±0.46/)mm vs.(9.43±0.57)mm;(53.04±2.98)/HP vs.(87.73±2.34)/HP) (both P＜0.01)on day 61.Impaired microvilli and organelles of the corneal and conjunctival epithelial cells were observed.Compared with PBS-treated group,PEG-treated group showed decrease in fluorescein [3(2.0,3.0) vs.1 (0.5,1.0)] and rose bengal scores [2 (2,3) vs.1 (0,1)] (both P＜0.001),increase in Schirmer Ⅰ test value scores [(7.00±0.71)mm vs.(5.18±0.46) mm,P＜0.05],increase in goblet cell density ((63.88±3.32)/HP vs.(53.04±2.98)/HP,P＜0.05) and improvement of grading scores of conjunctival epithelium on day 61.In addition,complete mierovilli and cell organelles were found in the corneal and conjunctival epithelial cells in the polyethylene glycol group.Conclusions Topical application of polyethylene glycol can decrease the ocular surface toxicity induced by benzalkonium chloride-preserved latanoprost. Key words: Polyethylene glycol; Latanoprost; Benzalkonium chloride; Ocular surface toxicity