On recycling earth pressure balance shield muck with residual foaming agent: defoaming and antifoaming investigations.

Earth pressure balance (EPB) shield is increasingly employed in metro tunnel construction, and causes a series of environmental, safety, and resource waste problems due to the disposal of a considerable amount of muck. In situ recycling of EPB shield muck is an effective solution, whereas the foam is generated by residual foaming agents used as the muck conditioning material during tunnelling, which often adsorbs clay particles and overflows the flocculation tank. To achieve defoaming and antifoaming during the reuse of muck, this study prepared novel eco-friendly silicone oil-polyether defoamers by condensation, compounding, and shear emulsification. Defoaming and antifoaming performances of different defoamers were tested using a modified Ross-Miles method and a scale model of field flocculation systems. The results indicated that a high efficiency in defoam and antifoam was characterized by chemical grafting of nano-SiO2 from silicone oils, uniform distribution and large size of grains, low viscosity, and surface tension. The defoamer dosage of 0.002-0.004 wt% near critical micelle concentration (CMC) for each defoamer is reasonable. Overall, the prepared hydroxyl silicone oil-glycerol polyoxypropylene ether (H-G) defoamer compared with other silicone oil-polyether defoamers and commercial defoamers presents the highest defoaming and antifoaming efficiency. Considering the effects of EPB shield muck, the H-G defoamer is least affected by the compound materials and increasing concentration of the commercial foaming agent. Nevertheless, the stability of the H-G emulsion system is weaker than that of the dimethyl silicone oil-glycerol polyoxypropylene ether (D-G) emulsion system after 1 month of sealed storage.

Characterizing Silicone Oil-Induced Protein Aggregation with Stimulated Raman Scattering Imaging.

Particles in biopharmaceutical products present high risks due to their detrimental impacts on product quality and safety. Identification and quantification of particles in drug products are important to understand particle formation mechanisms, which can help develop control strategies for particle formation during the formulation development and manufacturing process. However, existing analytical techniques such as microflow imaging and light obscuration measurement lack the sensitivity and resolution to detect particles with sizes smaller than 2 µm. More importantly, these techniques are not able to provide chemical information to determine particle composition. In this work, we overcome these challenges by applying the stimulated Raman scattering (SRS) microscopy technique to monitor the C-H Raman stretching modes of the proteinaceous particles and silicone oil droplets formed in the prefilled syringe barrel. By comparing the relative signal intensity and spectral features of each component, most particles can be classified as protein-silicone oil aggregates. We further show that morphological features are poor indicators of particle composition. Our method has the capability to quantify aggregation in protein therapeutics with chemical and spatial information in a label-free manner, potentially allowing high throughput screening or investigation of aggregation mechanisms.

Competitive Adsorption of a Monoclonal Antibody and Nonionic Surfactant at the PDMS/Water Interface.

Interfacial adsorption of monoclonal antibodies (mAbs) can cause structural deformation and induce undesired aggregation and precipitation. Nonionic surfactants are often added to reduce interfacial adsorption of mAbs which may occur during manufacturing, storage, and/or administration. As mAbs are commonly manufactured into ready-to-use syringes coated with silicone oil to improve lubrication, it is important to understand how an mAb, nonionic surfactant, and silicone oil interact at the oil/water interface. In this work, we have coated a polydimethylsiloxane (PDMS) nanofilm onto an optically flat silicon substrate to facilitate the measurements of adsorption of a model mAb, COE-3, and a commercial nonionic surfactant, polysorbate 80 (PS-80), at the siliconized PDMS/water interface using spectroscopic ellipsometry and neutron reflection. Compared to the uncoated SiO2 surface (mimicking glass), COE-3 adsorption to the PDMS surface was substantially reduced, and the adsorbed layer was characterized by the dense but thin inner layer of 16 Å and an outer diffuse layer of 20 Å, indicating structural deformation. When PS-80 was exposed to the pre-adsorbed COE-3 surface, it removed 60 wt % of COE-3 and formed a co-adsorbed layer with a similar total thickness of 36 Å. When PS-80 was injected first or as a mixture with COE-3, it completely prevented COE-3 adsorption. These findings reveal the hydrophobic nature of the PDMS surface and confirm the inhibitory role of the nonionic surfactant in preventing COE-3 adsorption at the PDMS/water interface.

Probing Molecular Interactions of Antibody Drugs, Silicone Oil, and Surfactant at Buried Interfaces In Situ.

Antibody drugs have been rapidly developed to cure many diseases including COVID-19 infection. Silicone oil is commonly used as a lubricant coating material for devices used in the pharmaceutical industry to store and administer antibody drug formulations. However, the interaction between silicone oil and antibody molecules could lead to the adsorption, denaturation, and aggregation of antibody molecules, impacting the efficacy of antibody drugs. Here, we studied the molecular interactions between antibodies and silicone oil in situ in real time. The effect of the surfactant on such interactions was also investigated. Specifically, the adsorption dynamics of a bispecific antibody (BsAb) onto a silicone oil surface without and with different concentrations of the surfactant PS80 in antibody solutions were monitored. Also the possible lowest effective PS80 concentrations that can prevent the adsorption of BsAb as well as a monoclonal antibody (mAb) onto silicone oil were measured. It was found that different concentrations of PS80 are required for preventing the adsorption of different antibodies. Both BsAB and mAB denature on silicone oil without a surfactant. However, for a low surfactant concentration in the solution, although the surfactant could not completely prevent the antibody from adsorption, it could maintain the native structures of adsorbed BsAb and mAb antibodies on silicone oil. This is important knowledge, showing that to prevent antibody aggregation on silicone oil it is not necessary to add surfactant to a concentration high enough to completely minimize protein adsorption.

The air entrainment and hydrodynamic shear of the liquid slosh in syringes.

Understanding the interface motion and hydrodynamic shear induced by the liquid sloshing during the insertion stage of an autoinjector can help improve drug product administration. We perform experiments to investigate the interfacial motion and hydrodynamic shear due to the acceleration and deceleration of syringes. The goal is to explore the role of fluid properties, air gap size, and syringe acceleration on the interface dynamics caused by autoinjector activation. We used a simplified autoinjector platform to record the syringe and liquid motion without any view obstruction. Water and silicone oil with the same viscosity are used as the model fluids. Particle Image Velocimetry (PIV) is employed to measure the velocity field. Simultaneous shadowgraph visualization captures the air entrainment. Our in-house PIV and image processing algorithms are used to quantify the hydrodynamic stress and interfacial area to investigate the effects of various autoinjector design parameters and fluid types on liquid sloshing. The results indicate that reducing the air gap volume and syringe acceleration/deceleration mitigate the interface area and effective shear. Moreover, the interfacial area and induced hydrodynamic stress decrease with the Fr=U/aD, where U is the interface velocity, a is the maximum syringe acceleration, and D is the syringe diameter.

Enhanced protein aggregation suppressor activity of N-acetyl-l-arginine for agitation-induced aggregation with silicone oil and its impact on innate immune responses.

Previously, N-acetyl-l-arginine (NALA) suppressed the aggregation of intravenous immunoglobulins (IVIG) more effectively and with a minimum decrease in transition temperature (Tm) than arginine monohydrochloride. In this study, we performed a comparative study with etanercept (commercial product: Enbrel®), where 25 mM arginine monohydrochloride (arginine) was added to the prefilled syringe. The biophysical properties were investigated using differential scanning calorimetry (DSC), dynamic light scattering (DLS), size-exclusion chromatography (SEC), and flow-imaging microscopy (FI). NALA retained the transition temperature of etanercept better than arginine, where arginine significantly reduced the Tm by increasing its concentration. End-over-end rotation was applied to each formulation for 5 days to accelerate protein aggregation and subvisible particle formation. Higher monomeric content was retained with NALA with a decrease in particle level. Higher aggregation onset temperature (Tagg) was detected for etanercept with NALA than arginine. The results of this comparative study were consistent with previous study, suggesting that NALA could be a better excipient for liquid protein formulations. Agitated IVIG and etanercept were injected into C57BL/6J female mice to observe immunogenic response after 24 h. In the presence of silicone oil, NALA dramatically reduced IL-1 expression, implying that decreased aggregation was related to reduced immunogenicity of both etanercept and IVIG.

Efficient and stable electrorheological fluids based on chestnut-like cobalt hydroxide coupled with surface-functionalized carbon dots.

Intrinsically polarized electrorheological fluids (ERFs) have better thermal stability than ERFs with polar molecules, so they have a broader application prospect. However, the electrorheological efficiency of the common intrinsically polarized ERF is still lower than 1500, which is related to the poor wettability between polarized materials and the continuous phase. Carbon dots (CDs) exhibit good stability, semiconductor properties and low toxicity. We prepared biomimetic chestnut-like cobalt hydroxide coupled with surface-functionalized CD particles (Co(OH)2@CDs) by a simple hydrothermal method. Then we prepared an ERF by mixing Co(OH)2@CDs with silicone oil and studied the effect of CDs on its rheology and electrorheology properties. The synergistic effect of the lipophilic groups on the surface of CDs and the biomimetic chestnut-like structure makes Co(OH)2@CDs exhibit good wettability with silicone oil, and the optimal zero-field viscosity of Co(OH)2@CDs-ERF is only 0.46 Pa s (particle mass fraction of 40%). Exceptional electrorheological efficiency (about 10 000, shear rate 0.1 s-1, 5 kV mm-1) and dynamic shear stress stability of optimal Co(OH)2@CDs-ERF can be attributed to the dielectric enhancement of the biomimetic chestnut-like structure coupled with the semiconductor properties of CDs. In addition, Co(OH)2@CDs-ERF has excellent anti-settling performance, outstanding thermal stability and low current density.

Physicochemical Properties of Explanted Silicone Oil After Use as an Intraocular Tamponade.

PURPOSE: We studied the effects of exposure to biological media within the eye, such as contamination with lipophilic and amphiphilic substances, on the physicochemical parameters of silicone oil used as an intraocular tamponade. METHODS: We removed silicone oil with visible emulsification from 15 patients and measured each sample for shear viscosity and surface tension. We induced in vitro emulsification with balanced salt solution. Using the zeta-potential, we evaluated the emulsion droplet's electrochemical stability. We repeated all experiments in a control group of unused oil. Electrochemical stability and viscosity were additionally measured in oils with high-molecular-weight components. RESULTS: We recovered silicone oils implanted between 30 and 506 days (mean, 196 days). Viscosity did not differ between explanted and control groups. Surface tension and zeta potential remained unchanged (P = 0.61 and P = 0.84, respectively). All oils showed a significant correlation of viscosity with temperature (P < 0.01 for all). Oils with added high-molecular-weight components showed a lower emulsion stability. CONCLUSIONS: Prolonged contact to hydrophilic biological media does not alter high-viscosity silicone oil's physicochemical parameters. During typical durations of intraocular use, lipophilic and amphiphilic molecules had no deleterious effect. The addition of high-molecular-weight components might decrease the silicone oil's electrochemical emulsion stability, possibly easing the confluence of emulsion droplets. TRANSLATIONAL RELEVANCE: Although the physicochemical parameters of silicone oils are not altered after clinically relevant durations within the eye, emulsion stability significantly differs between oil types.

Slippery Liquid-Like Solid Surfaces with Promising Antibiofilm Performance under Both Static and Flow Conditions.

Biofilms are central to some of the most urgent global challenges across diverse fields of application, from medicine to industries to the environment, and exert considerable economic and social impact. A fundamental assumption in anti-biofilms has been that the coating on a substrate surface is solid. The invention of slippery liquid-infused porous surfaces─a continuously wet lubricating coating retained on a solid surface by capillary forces─has led to this being challenged. However, in situations where flow occurs, shear stress may deplete the lubricant and affect the anti-biofilm performance. Here, we report on the use of slippery omniphobic covalently attached liquid (SOCAL) surfaces, which provide a surface coating with short (ca. 4 nm) non-cross-linked polydimethylsiloxane (PDMS) chains retaining liquid-surface properties, as an antibiofilm strategy stable under shear stress from flow. This surface reduced biofilm formation of the key biofilm-forming pathogens Staphylococcus epidermidis and Pseudomonas aeruginosa by three-four orders of magnitude compared to the widely used medical implant material PDMS after 7 days under static and dynamic culture conditions. Throughout the entire dynamic culture period of P. aeruginosa, SOCAL significantly outperformed a typical antibiofilm slippery surface [i.e., swollen PDMS in silicone oil (S-PDMS)]. We have revealed that significant oil loss occurred after 2-7 day flow for S-PDMS, which correlated to increased contact angle hysteresis (CAH), indicating a degradation of the slippery surface properties, and biofilm formation, while SOCAL has stable CAH and sustainable antibiofilm performance after 7 day flow. The significance of this correlation is to provide a useful easy-to-measure physical parameter as an indicator for long-term antibiofilm performance. This biofilm-resistant liquid-like solid surface offers a new antibiofilm strategy for applications in medical devices and other areas where biofilm development is problematic.

Towards quantification and differentiation of protein aggregates and silicone oil droplets in the low micrometer and submicrometer size range by using oil-immersion flow imaging microscopy and convolutional neural networks.

Biopharmaceutical product characterization benefits from the quantification and differentiation of unwanted protein aggregates and silicone oil droplets to support risk assessment and control strategies as part of the development. Flow imaging microscopy is successfully applied to differentiate the two impurities in the size range larger than about 5 µm based on their morphological appearance. In our study we applied the combination of oil-immersion flow imaging microscopy and convolutional neural networks to extend the size range below 5 µm. It allowed to differentiate and quantify heat stressed therapeutic monoclonal antibody aggregates from artificially generated silicone oil droplets with misclassification rates of about 10% in the size range between 0.3 and 5 µm. By comparing the misclassifications across the tested size range, particles in the low submicron size range were particularly difficult to differentiate as their morphological appearance becomes very similar.

Rapid aggregation of therapeutic monoclonal antibodies by bubbling induced air/liquid interfacial and agitation stress at different conditions.

Degradation of therapeutic monoclonal antibodies (mAb) due to interfacial agitation through air bubbling was investigated. Samples containing mAb in phosphate buffered saline were subjected to rapid bubbling by using a peristaltic pump at an air flow rate of 11.5 mL/min. Samples were analyzed by visual observation, UV-Vis, fluorescence, circular dichroism and infrared spectroscopy, size-exclusion chromatography (SEC), dynamic light scattering, microscopy, and cell-based activity assays. The stressed samples showed increasing turbidity with bubbling time, with mAb1 showing a protein loss of 53% in the supernatant at the latest time point (240 min), indicating formation of sub-visible and visible aggregates. Aggregate rich samples exhibited altered secondary structure and higher hydrophobicity with 40% reduction in activity. The supernatants of the stressed samples showed unchanged secondary and tertiary structure without the presence of any oligomers in SEC. Furthermore, the impact of various factors that could affect aggregation was investigated and it was found that the extent of aggregation was affected by protein concentration, sample volume, presence of surfactants, temperature, air flow rate, and presence of silicone oil. In conclusion, exposure to air/liquid interfacial stress through bubbling into liquid mAb samples effectively generated sub-visible and visible aggregates, making air bubbling an attractive approach for interfacial stress degradation studies of mAbs.

Bioinspired Oil-Infused Slippery Surfaces with Water and Ion Barrier Properties.

Encapsulation materials play an important role in many applications including wearable electronics, medical devices, underwater robotics, marine skin tagging system, food packaging, and energy conversation and storage devices. To date, all the encapsulation materials, including polymer layers and inorganic materials, are solid materials. These solid materials suffer from limited barrier lifetimes due to pinholes, cracks, and nanopores or from complicated fabrication processes and limited stretchability for interfacing with complex 3D surfaces. This paper reports a solution to this material challenge by demonstrating bioinspired oil-infused slippery surfaces with excellent waterproof property for the first time. A water vapor transmission test shows that locking a thin layer of oil on the silicone elastomer improves the water vapor barrier performance by three orders of magnitude. Accelerated lifetime tests suggest robust water barrier characteristics that approach 226 days at 37 °C even under severe mechanical damage. A combination of temperature- and thickness-dependent experimental measurements and reaction-diffusion modeling reveals the key waterproof property. In addition to serving as a barrier to water, the oil-infused surface demonstrates an attractive ion barrier property. All these exceptional properties suggest the potential applications of slippery surfaces as encapsulation materials for medical devices, underwater electronics, and many others.

Adsorption and Aggregation of Monoclonal Antibodies at Silicone Oil-Water Interfaces.

Monoclonal antibody (mAb) therapies are rapidly growing for the treatment of various diseases like cancer and autoimmune disorders. Many mAb drug products are sold as prefilled syringes and vials with liquid formulations. Typically, the walls of prefilled syringes are coated with silicone oil to lubricate the surfaces during use. MAbs are surface-active and adsorb to these silicone oil-solution interfaces, which is a potential source of aggregation. We studied formulations containing two different antibodies, mAb1 and mAb2, where mAb1 aggregated more when agitated in the presence of an oil-water interface. This directly correlated with differences in surface activity of the mAbs, studied with interfacial tension, surface mass adsorption, and interfacial rheology. The difference in interfacial properties between the mAbs was further reinforced in the coalescence behavior of oil droplets laden with mAbs. We also looked at the efficacy of surfactants, typically added to stabilize mAb formulations, in lowering adsorption and aggregation of mAbs at oil-water interfaces. We showed the differences between poloxamer-188 and polysorbate-20 in competing with mAbs for adsorption to interfaces and in lowering particulate and overall aggregation. Our results establish a direct correspondence between the adsorption of mAbs at oil-water interfaces and aggregation and the effect of surfactants in lowering aggregation by competitively adsorbing to these interfaces.

High particle variability across siliconized and oil-free syringes and needles from the same lots.

Previous studies have reported silicone oil (SO) applied to needles and syringes in the vitreous of patients after intravitreal injections. We evaluated four syringes (SR 1-mL insulin, Saldanha-Rodrigues; BD 1-mL Tuberculin Slip Tip, Becton-Dickinson; BD Ultra-Fine 0.3 mL, HSW Norm-Ject Tuberculin, Henke Sass Wolf) and 10 needles (BD PrecisionGlide 27- and 30-gauge (G); BD Eclipse and JBP Nanoneedle 27-, 30-, 33- and 34-G; TSK Invisible Needle and 27 and 30-G Steriject Control Hub). The protein-free buffer samples injected into the syringes and needles under study were collected in an Eppendorf tube and taken to Flow imaging microscopy, that characterized the concentration and morphology of the microsized particles. The number of particles was analyzed. The coefficients of variation (CV) were the primary outcome. The Feltz and Miller test compared the CVs. The significance level was 5%. Numerous particles and high CVs were associated with both devices, needles and syringes; the comparisons among them did not reach significance. The BD Ultrafine 0.3 mL syringe (149.7%) had the highest CV and the SO-free HSW Norm-Ject (66.4%) syringe the lowest, and the TSK Invisible needle (149.5%) had the highest and the BD Precision Glide 30G needle (35.9%) needle the lowest. In conclusion, particle release, including those with SO morphology, varied greatly among instruments, even from the same lots, which is relevant considering that fewer particles are injected into some eyes compared with others.

Oil-Immersion Flow Imaging Microscopy for Quantification and Morphological Characterization of Submicron Particles in Biopharmaceuticals.

Flow imaging microscopy (FIM) is widely used to analyze subvisible particles starting from 2 µm in biopharmaceuticals. Recently, an oil-immersion FIM system emerged, the FlowCam Nano, designed to enable the characterization of particle sizes even below 2 µm. The aim of our study was to evaluate oil-immersion FIM (by using FlowCam Nano) in comparison to microfluidic resistive pulse sensing and resonant mass measurement for sizing and counting of particles in the submicron range. Polystyrene beads, a heat-stressed monoclonal antibody formulation and a silicone oil emulsion, were measured to assess the performance on biopharmaceutical relevant samples, as well as the ability to distinguish particle types based on instrument-derived morphological parameters. The determination of particle sizes and morphologies suffers from inaccuracies due to a low image contrast of small particles and light-scattering effects. The ill-defined measured volume impairs an accurate concentration determination. Nevertheless, FlowCam Nano in its current design complements the limited toolbox of submicron particle analysis of biopharmaceuticals by providing particle images in a size range that was previously not accessible with commercial FIM instruments.

Immobilized Droplet Arrays in Thermosetting Oil for Dynamic Proteolytic Assays of Single Cells.

Matrix metalloproteinases (MMPs) play an important role in tumor progression. The study of dynamic MMPs activity at the single-cell level can dissect tumor heterogeneity in the time domain and facilitate finding out more efficient clinical solutions for tumor treatment. Due to the fluidity of the carrier oil, the existing droplet-based methods for single-cell MMP analysis rarely have the capability to track proteolytic assays in droplets continuously. Therefore, we describe a thermosetting oil for real-time monitoring of MMP assays in droplets, which can immobilize droplets by transforming into solid after droplet generation. The solidification of this oil can be accomplished in 33 min at 37 °C, basing on the hydrosilation of vinyl silicone oil and hydrosilicone oil without other inducers (e.g. UV, Ca2+). Through monitoring the MMP assays of single cells, the reaction rates can be calculated according to real-time fluorescent curves, showing significant cell heterogeneity in MMP activity. Moreover, the dynamic MMP activity reveals that some of the A549 cells transiently secrete MMP. In conclusion, the thermosetting oil enables immobilize droplets to achieve real-time monitoring of single-cell proteolytic activity without impairing the flexibility of droplet microfluidics and has a potential in other cell-based assays for providing dynamic information at high resolutions.

Enhanced electrorheological activity of porous chitosan particles.

Novel porous filler for electrorheological fluids was fabricated from chitosan via freeze drying technique. An exceptional electrorheological effect was discovered in suspensions of polydimethylsiloxane (silicone oil) filled by highly porous chitosan particles. The electrorheological activity was studied by rotational rheometry and visualized by optical microscopy. High porosity of the filler allows preparing highly efficient electrorheological fluids at rather low (< 1 wt%) concentration of dispersed phase. The mechanism of chain-like structure formation was considered. The electrorheological behavior of suspensions and the filler structural organization at different concentration were comprehended in terms of dielectric properties. The rheological data were approximated by Bingham and Cho-Choi-Jhon equations. The sedimentation stability of chitosan suspensions in polydimethylsiloxane was significantly affected by particles porosity.

LABORATORY EVALUATION OF INTRAOCULAR SILICONE OIL REMOVED AFTER 23 YEARS IN SITU.

PURPOSE: To report the clinicopathologic correlation and biochemical analysis of silicone oil removed after 23 years in an eye. METHODS: A 63-years-old man with a history of HIV/AIDS and cytomegalovirus retinitis, status post retinal detachment repair with silicone oil at the age of 39 years, presented with several weeks of worse vision. He was found to have a shallow fovea-off tractional retinal detachment. After the silicone oil was removed during retinal detachment repair, it was analyzed by Fourier-transform infrared spectroscopy and gas chromatography with mass spectrometry. RESULTS: In addition to cyclic and linear silicone oil, cholesterol was found in the removed silicone oil, which was not present in unused silicone oil samples. No other chemical alterations were identified in the extracted silicone oil. CONCLUSION: Silicone oil left inside an eye over an extended period may extract lipophilic substances from adjacent tissue, with possible pathophysiologic effects. However, no other major potentially toxic substance was identified from the long-standing silicone oil sample, suggesting relative chemical stability of the tamponade agent over time.

PARTICULATE MATTER FROM SYRINGES USED FOR INTRAVITREAL INJECTIONS.

BACKGROUND: Syringes containing anti-vascular endothelial growth factor drugs to treat retinal diseases are prepared in different ways by various parties with syringe selection, preparation, and storage conditions affecting the risk of injecting particles into the vitreous. This study examines particle loads from various syringes over time. METHODS: Four syringes were studied: two plastic transfer syringes lubricated with silicone oil or oleamide, a glass syringe with baked-on silicone, and a lubricant-free polymer syringe. Syringes were rinsed with water or filled with buffer and analyzed over time; particles were quantified by flow imaging. Particle formation in a bevacizumab formulation was also characterized. RESULTS: Insulin syringes consistently showed very high particle counts. Oleamide-lubricated syringes had substantially fewer particles, but showed appreciable increases over time (leading to visible particles). Baked-on silicone glass syringes and lubricant-free polymer syringes both showed low particle levels ≥10 µm. Lubricant-free syringes showed the lowest particle levels ≥1 µm and the lowest particle levels with bevacizumab agitation. CONCLUSION: Syringes have different intrinsic particle loads which can contribute to particle loads in the delivered drug. Oleamide-lubricated transfer syringes, commonly used for bevacizumab repackaging, have time-dependent particle loads and are associated with the formation of visible particles beyond 30 days of storage.

Silicone oil in vitreoretinal surgery: indications, complications, new developments and alternative long-term tamponade agents.

Silicone oil (SO) has been used as a long-term tamponade agent in the treatment of complicated vitreoretinal diseases for about half a century, during which time many advances in surgical techniques and technologies have been made. This review summarizes the chemical and physical properties of SO, its indications and complications, including particularly emulsification. The mechanisms and risk factors for emulsification are discussed, as well as novel strategies for its effective removal. Finally, the review focuses on new improved formulations of SO, including research into slow-release pharmacological agents within SO and provides an overview of alternatives to SO for the purpose of long-term tamponade that are being developed.