ABSTRACT
OBJECTIVES: Silicone oil (SO) is a commonly used intraocular tamponade in the treatment of rhegmatogenous retinal detachment (RRD). SO emulsification is a common complication after SO injection. This study aimed to investigate correlations between SO emulsification signs on ultrasound biomicroscopy (UBM) and the real number/size of SO droplets. METHODS: An observational, cross-sectional study. Thirty-five RRD patients (19 males; 35 eyes) who underwent pars plana vitrectomy and SO injection were enrolled in the study. SO emulsification signs on UBM (endothelial deposits, floating droplets, ghost images, hyperoleon, anterior chamber angle impregnation, anterior iris surface impregnation, posterior iris surface impregnation and ciliary body impregnation) were acquired and quantified two days before SO removal, while real number/size of the SO droplets with a diameter in 0.4-20â µm in the first 2â mL washout fluid collected intraoperatively during SO removal were assessed by Coulter counter. Then the correlations between these values were explored. RESULTS: The grade of tissue impregnation and hyperoleon area in the anterior chamber demonstrated significant correlations with the number of large (5-20â µm) SO droplets (r = 0.336; P = 0.048 and r = 0.350; P = 0.039, respectively); however, no significant correlations were observed with the total number of droplets (0.4-20â µm)or the number of small (0.4-5â µm) droplets (both P ï¼ 0.05). CONCLUSION: The UBM quantitative grade of tissue impregnation and hyperoleon area in the anterior chamber could provide a noninvasive overview of the actual degree of SO emulsification before SO removal surgery.
Subject(s)
Microscopy, Acoustic , Retinal Detachment , Silicone Oils , Vitrectomy , Humans , Silicone Oils/chemistry , Microscopy, Acoustic/methods , Male , Female , Retinal Detachment/surgery , Retinal Detachment/diagnostic imaging , Cross-Sectional Studies , Middle Aged , Aged , Emulsions , Adult , Eye/diagnostic imagingABSTRACT
This study investigates the impact of intravenous (IV) infusion protocols on the stability of Intravenous Immunoglobulin G (IVIG) and Rituximab, with a particular focus on subvisible particle generation. Infusion set based on peristaltic movement (Medifusion DI-2000 pump) was compared to a gravity-based infusion system (Accu-Drip) at different flow rates. The impacts of different diluents (0.9 % saline and 5.0 % dextrose) and plastic syringes with or without silicone oil (SO) were also investigated. The results from the aforementioned particular case demonstrated that peristaltic pumps generated high levels of subvisible particles (prominently < 25 µm), exacerbated by increasing flow rates, specifically in formulations lacking surfactants. Other factors, such as diluent type and syringe composition, also increased the number of subvisible particles. Strategies that can help overcome these complications include surfactant addition as well as the use of SO-free syringes and a gravity infusion system, which aid in reducing particle formation and preserving antibody monomer during administration. Altogether, these findings highlight the importance of the careful selection of formulations and infusion protocols to minimize particle generation during IV infusion both for patients' safety and treatment efficacy.
Subject(s)
Drug Stability , Immunoglobulins, Intravenous , Rituximab , Syringes , Rituximab/administration & dosage , Rituximab/chemistry , Infusions, Intravenous , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/chemistry , Infusion Pumps , Surface-Active Agents/chemistry , Silicone Oils/chemistry , Drug Packaging , Plastics/chemistry , Glucose/chemistry , HumansABSTRACT
STERIS and W.L. GORE collaborated on a case study testing the compatibility of a new prefilled syringe plunger design with VHP terminal sterilization. VHP chamber conditions require deep vacuum pulsing, which may represent challenges to prefilled syringe container integrity. The growing industry trend toward VHP sterilization is driven by the FDA search for alternative sterilization methods to EO and the recent publication of a VHP specific process standard. The purpose of the study is to test and report compatibility of the new 0.5 mL GORE IMPROJECT plunger, a silicone free syringe solution for ophthalmic application, with VHP sterilization. Various challenges have been reported when using conventional, siliconized, prefilled syringe systems for intravitreal injections such as subvisible particles, inflammation, silicone floaters, and intraocular pressure increases. The GORE plunger eliminates the need for silicone oil as a lubricant on the plunger and barrel, while meeting strict container closure and terminal sterilization requirements of ophthalmic applications. This case study presents successful results of deep vacuum VHP terminal sterilization process compatibility with the GORE plunger design and material composition. Test results include primary container integrity, stopper off-gassing/ingress, and visual inspection. Principles of VHP vacuum sterilization process, test cycle configuration, and its main parameters are presented.
Subject(s)
Hydrogen Peroxide , Sterilization , Syringes , Sterilization/methods , Syringes/standards , Hydrogen Peroxide/chemistry , Equipment Design , Vacuum , Volatilization , Drug Packaging/standards , Technology, Pharmaceutical/methods , Technology, Pharmaceutical/instrumentation , Technology, Pharmaceutical/standards , Silicone Oils/chemistry , Intravitreal Injections/instrumentationABSTRACT
Silicone oil (SO) migration into the drug product of combination products for biopharmaceuticals during storage is a common challenge. As the inner barrel surface is depleted of SO the extrusion forces can increase compromising the container functionality. In this context we investigated the impact of different formulations on the increase in gliding forces in a spray-on siliconized pre-filled syringe upon storage at 2-8 °C, 25 °C and 40 °C for up to 6 months. We tested the formulation factors such as surfactant type, pH, and ionic strength in the presence of one monoclonal antibody (mAb) as well as compared three mAbs in one formulation. After 1 month at 40 °C, the extrusion forces were significantly increased due to SO detachment dependent on the fill medium. The storage at 40 °C enhanced the SO migration process but it could also be observed at lower storage temperatures. Regarding the formulation factors the tendency for SO migration was predominantly dependent on the presence and type of surfactant. Interestingly, when varying the mAb molecules, one of the proteins showed a rather stabilizing effect on the SO layer resulting into higher container stability. In contrast to the formulation factors, those different stability outcomes could not be explained by interfacial tension (IFT) measurements at the SO interface. Further characterization of the mAb molecules regarding interfacial rheology and conformational stability were not adequately able to explain the observed difference. Solely a hydrophobicity ranking of the molecules correlated to the stability outcome. Further investigations are needed to clarify the role of the protein in the SO detachment process and to understand the cause for the stabilization. However, the study clearly demonstrated that the protein itself plays a critical role in the SO detachment process and underlined the importance to include verum for container stability.
Subject(s)
Antibodies, Monoclonal , Biological Products , Drug Stability , Drug Storage , Silicone Oils , Surface-Active Agents , Biological Products/chemistry , Antibodies, Monoclonal/chemistry , Silicone Oils/chemistry , Surface-Active Agents/chemistry , Drug Packaging/methods , Temperature , Hydrogen-Ion Concentration , Chemistry, Pharmaceutical/methods , Syringes , Osmolar Concentration , Drug Combinations , Silicones/chemistryABSTRACT
Purpose: First- (monomers), second- (pre-gelated), and third- (in situ gelating after injection) generation hydrogels were previously introduced to replace the vitreous body after vitrectomy surgery. In this study, we evaluated the surgical, optical, and viscoelastic properties of vitreous body replacement hydrogels before and after an accelerated aging protocol previously applied to intraocular implants. Methods: Measurements of injection force, removal speed using a clinically established vitrectomy setup, as well as evaluation of forward light scattering and viscoelastic properties before and after an accelerated aging protocol were conducted. Results were compared to porcine and human vitreous bodies, as well as currently clinically applied lighter- and heavier-than-water silicone oils. Results: Removal speed of all tested hydrogels is substantially lower than the removal speed of porcine vitreous body (0.2 g/min vs. 2.7 g/min for the best performing hydrogel and porcine vitreous body, respectively). Forward light scattering in second-generation vitreous body replacement hydrogels was higher after the aging process than the straylight of the average 70-year-old vitreous body (9.4 vs. 5.5 deg2/sr, respectively). The viscoelastic properties of all hydrogels did not change in a clinically meaningful manner; however, trends toward greater stiffness and greater elasticity after aging were apparent. Conclusions: This study demonstrates surgical weaknesses of the hydrogels that need to be addressed before clinical use, especially low removal speed. Pre-linked hydrogels (second-generation) showed inferior performance regarding surgical properties compared to in situ gelating hydrogels (third-generation). Translational Relevance: This study highlights possible pitfalls regarding surgical and optical properties when applying vitreous replacement hydrogels clinically.
Subject(s)
Hydrogels , Silicone Oils , Vitrectomy , Vitreous Body , Vitreous Body/surgery , Animals , Hydrogels/chemistry , Silicone Oils/chemistry , Swine , Vitrectomy/methods , Viscosity , Humans , Elasticity , Aged , Aging/physiologyABSTRACT
Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography-tandem mass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13 ± 7.21 nm size and 26.45 ± 2.09 mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions were more likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.
[Box: see text].
Subject(s)
Cyclosporine , Emulsions , Etodolac , Rabbits , Animals , Emulsions/chemistry , Cyclosporine/pharmacokinetics , Cyclosporine/administration & dosage , Cyclosporine/chemistry , Etodolac/chemistry , Tissue Distribution , Particle Size , Dry Eye Syndromes/drug therapy , Castor Oil/chemistry , Cations/chemistry , Silicone Oils/chemistry , Olive Oil/chemistry , Cornea/drug effects , Cornea/metabolism , Ophthalmic Solutions/chemistry , Humans , Drug LiberationABSTRACT
Indwelling medical catheters are frequently utilized in medical procedures, but they are highly susceptible to infection, posing a vital challenge for both health workers and patients. In this study, the superhydrophobic micro-nanostructure surface was constructed on the surface of thermoplastic polyurethane (TPU) membrane using heavy calcium carbonate (CaCO3) template. To decrease the surface free energy, hydroxyl silicone oil was grafted onto the surface, forming a super-hydrophobic surface. The water contact angle (WCA) increased from 91.1° to 143 ± 3° when the concentration of heavy calcium CaCO3 was 20% (weight-to-volume (w/v)). However, the increased WCA was unstable and tended to decrease over time. After grafting hydroxyl silicone oil, the WCA rose to 152.05 ± 1.62° and remained consistently high for a period of 30 min. Attenuated total reflection infrared spectroscopy (ATR-FTIR) analysis revealed a chemical crosslinking between silicone oil and the surface of TPU. Furthermore, Scanning electron microscope (SEM) image showed the presence of numerous nanoparticles on the micro surface. Atomic force microscope (AFM) testing indicated a significant improvement in surface roughness. This method of creating a hydrophobic surface demonstrated several advantages, including resistance to cell, bacterial, protein, and platelet adhesion and good biosecurity. Therefore, it holds promising potential for application in the development of TPU-based medical catheters with antibacterial properties.
Subject(s)
Hydrophobic and Hydrophilic Interactions , Polyurethanes , Silicone Oils , Surface Properties , Polyurethanes/chemistry , Silicone Oils/chemistry , Calcium Carbonate/chemistry , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Mice , Water/chemistry , Temperature , Staphylococcus aureus/drug effects , Materials TestingABSTRACT
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.
Subject(s)
Antifoaming Agents , Polymers , Propylene Glycols , Silicone Oils , Antifoaming Agents/chemistry , Antifoaming Agents/pharmacology , Silicone Oils/chemistry , Emulsions/chemistry , Glycerol , Surface-Active Agents , EthersABSTRACT
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.
Subject(s)
Protein Aggregates , Silicone Oils , Silicone Oils/chemistry , Spectrum Analysis, Raman , Proteins/chemistry , Microscopy , Particle SizeABSTRACT
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.
Subject(s)
Antibodies, Monoclonal , Surface-Active Agents , Surface-Active Agents/chemistry , Adsorption , Antibodies, Monoclonal/chemistry , Silicon Dioxide , Silicone Oils/chemistry , Polysorbates/chemistry , DimethylpolysiloxanesABSTRACT
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.
Subject(s)
Antibodies, Bispecific , COVID-19 , Humans , Silicone Oils/chemistry , Surface-Active Agents/chemistry , Excipients/chemistry , Adsorption , Antibodies, Monoclonal/chemistry , LubricantsABSTRACT
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.
Subject(s)
Hydrodynamics , Syringes , Silicone Oils/chemistry , Rheology , WaterABSTRACT
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.
Subject(s)
Protein Aggregates , Silicone Oils , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Etanercept/chemistry , Female , Immunity, Innate , Immunoglobulins, Intravenous , Mice , Mice, Inbred C57BL , Silicone Oils/chemistryABSTRACT
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.
Subject(s)
Carbon , Silicone Oils , Carbon/chemistry , Cobalt/chemistry , Hydroxides , Silicone Oils/chemistryABSTRACT
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.
Subject(s)
Oils , Silicone Oils , Emulsions , Humans , Silicone Oils/chemistry , Surface Tension , ViscosityABSTRACT
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 surfacesâa continuously wet lubricating coating retained on a solid surface by capillary forcesâhas 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.
Subject(s)
Biofilms/growth & development , Dimethylpolysiloxanes/chemistry , Silicone Oils/chemistry , Biofilms/drug effects , Biomass , Dimethylpolysiloxanes/pharmacology , Hydrophobic and Hydrophilic Interactions , Porosity , Pseudomonas aeruginosa/physiology , Staphylococcus epidermidis/physiology , Surface Properties , WettabilityABSTRACT
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.
Subject(s)
Antibodies, Monoclonal/pharmacology , Chemistry Techniques, Analytical/methods , Protein Aggregates , Silicone Oils/chemistry , Biological Products/pharmacology , Biological Products/standards , Humans , Immersion , Liposomes , Machine Learning , Microscopy/methods , Neural Networks, Computer , Particle SizeABSTRACT
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.
Subject(s)
Antibodies, Monoclonal/chemistry , Surface-Active Agents/chemistry , Chemistry, Pharmaceutical , Chromatography, Gel , Circular Dichroism , Dynamic Light Scattering , Hydrophobic and Hydrophilic Interactions , Silicone Oils/chemistry , TemperatureABSTRACT
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.
Subject(s)
Fluorocarbons/chemistry , Oils/chemistry , Silicone Elastomers/chemistry , Hydrophobic and Hydrophilic Interactions , Materials Testing , Permeability , Silicone Oils/chemistry , Steam , Surface Properties , Water/chemistryABSTRACT
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.