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1.
J Pharm Sci ; 113(4): 1054-1060, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37863428

RESUMO

Producing solid-state formulations of biologics remains a daunting task despite the prevalent use of lyophilization and spray drying technologies in the biopharmaceutical industry. The challenges include protein stability (temperature stresses), high capital costs, particle design/controllability, shortened processing times and manufacturing considerations (scalability, yield improvements, aseptic operation, etc.). Thus, scientists/engineers are constantly working to improve existing methodologies and exploring novel dehydration/powder-forming technologies. Microglassification™ is a dehydration technology that uses solvent extraction to rapidly dehydrate protein formulations at ambient temperatures, eliminating the temperature stress experienced by biologics in traditional lyophilization and spray drying methods. The process results in microparticles that are spherical, dense, and chemically stable. In this study, we compared the molecular stability of a monoclonal antibody formulation processed by lyophilization to the same formulation processed using Microglassification™. Both powders were placed on stability for 3 months at 40 °C and 6 months at 25 °C. Both dehydration methods showed similar chemical stability, including percent monomer, charge variants, and antigen binding. These results show that Microglassification™ is viable for the production of stable solid-state monoclonal antibody formulations.


Assuntos
Produtos Biológicos , Química Farmacêutica , Humanos , Química Farmacêutica/métodos , Anticorpos Monoclonais/química , Desidratação , Liofilização/métodos , Estabilidade de Medicamentos , Pós
2.
J Pharm Sci ; 112(3): 820-829, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36336103

RESUMO

In the manufacturing of therapeutic monoclonal antibodies (mAbs), the final steps of the purification process are typically ultrafiltration/diafiltration (UF/DF), dilution, and conditioning. These steps are developed such that the final drug substance (DS) is formulated to the desired mAb, buffer, and excipient concentrations. To develop these processes, process and formulation development scientists often perform experiments to account for the Gibbs-Donnan and volume-exclusion effects during UF/DF, which affect the output pH and buffer concentration of the UF/DF process. This work describes the development of an in silico model for predicting the DS pH and buffer concentration after accounting for the Gibbs-Donnan and volume-exclusion effects during the UF/DF operation and the subsequent dilution and conditioning steps. The model was validated using statistical analysis to compare model predictions against experimental results for nine molecules of varying protein concentrations and formulations. In addition, our results showed that the structure-based in silico approach used to calculate the protein charge was more accurate than a sequence-based approach. Finally, we used the model to gain fundamental insights about the Gibbs-Donnan effect by highlighting the role of the protein charge concentration (the protein concentration multiplied with protein charge at the formulation pH) on the Gibbs-Donnan effect. Overall, this work demonstrates that the Gibbs-Donnan and volume-exclusions effects can be predicted using an in silico model, potentially alleviating the need for experiments.


Assuntos
Anticorpos Monoclonais , Ultrafiltração , Ultrafiltração/métodos , Anticorpos Monoclonais/química , Excipientes/química
3.
J Pharm Sci ; 111(8): 2172-2179, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35640732

RESUMO

Physical instability of aqueous drug solutions, such as precipitation upon storage, has so far been difficult to predict or model. Understanding the molecular basis of such phenomena can help mitigate by influencing the product composition and by providing a mechanistic basis of experimental and in silico investigations. In this study, inconsistent precipitation of a model drug, GNE-01 in aqueous solutions was investigated. Chromatographic analyses of the drug solution that showed precipitation upon storage versus the one that did not indicate lack of covalent modification or degradation of the drug, suggesting that the precipitation was a physical phenomenon. Molecular level investigations were conducted using surface tension measurement and nuclear magnetic resonance (NMR) spectroscopy. The studies revealed self-association of the weakly basic drug in solution at slightly acidic pH values which was strengthened by the presence of polyionic excipients. The role of polyionic excipients in facilitating drug precipitation on storage was indicative of shifting solution equilibria in favor of a lower solubility drug-excipient complex. This study highlighted the importance of molecular understanding in mitigating difficult to predict physical instability of self-associating drugs in solution.


Assuntos
Excipientes , Água , Excipientes/química , Solubilidade , Tensão Superficial
4.
Pharm Res ; 39(3): 563-575, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35277841

RESUMO

PURPOSE: Polysorbates (PS) contain polyoxyethylene (POE) sorbitan/isosorbide fatty acid esters that can partially hydrolyze over time in liquid drug products to generate degradants and a remaining intact PS fraction with a modified ester distribution. The degradants are composed of free fatty acids (FFAs) --primarily lauric acid for PS20 and oleic acid for PS80-- and POE head groups. We previously demonstrated that under IV bag agitation conditions, mAb1 (a surface-active IgG4) aggregation increased with increasing amounts of degradants for PS20 but not for PS80. The purpose of this work is to understand the mechanism behind this observation. METHODS: The surface tension of the remaining intact PS fraction without degradants was modeled and compared with that of enzymatically degraded PS solutions. Next, mAb1 aggregation in saline was measured in the presence of laurate and oleate salts during static storage. Lastly, colloidal and conformational stability of mAb1 in the presence of these salts was investigated through differential scanning fluorimetry and dynamic light scattering under IV bag solution conditions. RESULTS: The surface tension was primarily influenced by FFAs rather than the modified ester distribution of the remaining intact PS. MAb1 bulk aggregation increased in the presence of laurate but not oleate salts. Both salt types increased the melting temperature of mAb1 indicating FFA-mAb1 interactions. However, only laurate salt increased mAb1 self-association potentially explaining the higher aggregation propensity in its presence. CONCLUSION: Our results help explain the observed differences between hydrolytically degraded PS20 and PS80 in affecting mAb1 aggregation under IV bag agitation conditions.


Assuntos
Anticorpos Monoclonais , Polissorbatos , Ésteres , Ácidos Graxos não Esterificados , Hidrólise , Ácido Oleico , Polietilenoglicóis , Polissorbatos/metabolismo , Sais , Tensoativos
5.
Pharm Res ; 38(9): 1563-1583, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34495486

RESUMO

PURPOSE: To evaluate a modified high purity polysorbate 20 (RO HP PS20)-with lower levels of stearate, palmitate and myristate esters than the non-modified HP PS20-as a surfactant in biopharmaceutical drug products (DP). RO HP PS20 was designed to provide functional equivalence as a surfactant while delaying the onset of free fatty acid (FFA) particle formation upon hydrolytic degradation relative to HP PS20. METHODS: Analytical characterization of RO HP PS20 raw material included fatty acid ester (FAE) distribution, higher order ester (HOE) fraction, FFA levels and trace metals. Functional assessments included 1) vial and intravenous bag agitation; 2) oxidation via a placebo and methionine surrogate study; and 3) hydrolytic PS20 degradation studies to evaluate FFA particle formation with and without metal nucleation. RESULTS: Interfacial protection and oxidation propensity were comparable between the two polysorbates. Upon hydrolytic degradation, FFA particle onset was delayed in RO HP PS20. The delay was more pronounced when HOEs of PS20 were preferentially degraded. Furthermore, the hydrolytic degradants of RO HP PS20 formed fewer particles in the presence of spiked aluminum. CONCLUSION: This work highlights the criticality of having tighter control on long chain FAE levels of PS20 to reduce the occurrence of FFA particle formation upon hydrolytic degradation and lower the variability in its onset. By simultaneously meeting compendial PS20 specifications while narrowing the allowable range for each FAE and shifting its composition towards the shorter carbon chain species, RO HP PS20 provides a promising alternative to HP PS20 for biopharmaceutical DPs.


Assuntos
Ácidos Graxos não Esterificados/química , Polissorbatos/química , Produtos Biológicos/química , Química Farmacêutica/métodos , Ésteres/química , Hidrólise , Oxirredução , Tensoativos/química
6.
Biomacromolecules ; 22(8): 3386-3395, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34213889

RESUMO

There are 150 million people with diabetes worldwide who require insulin replacement therapy, and the prevalence of diabetes is rising the fastest in middle- and low-income countries. The current formulations require costly refrigerated transport and storage to prevent loss of insulin integrity. This study shows the development of simple "drop-in" amphiphilic copolymer excipients to maintain formulation integrity, bioactivity, pharmacokinetics, and pharmacodynamics for over 6 months when subjected to severe stressed aging conditions that cause current commercial formulation to fail in under 2 weeks. Further, when these copolymers are added to Humulin R (Eli Lilly) in original commercial packaging, they prevent insulin aggregation for up to 4 days at 50 °C compared to less than 1 day for Humulin R alone. These copolymers demonstrate promise as simple formulation additives to increase the cold chain resilience of commercial insulin formulations, thereby expanding global access to these critical drugs for treatment of diabetes.


Assuntos
Diabetes Mellitus , Insulina , Excipientes , Humanos , Insulina Regular Humana , Refrigeração
7.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34301872

RESUMO

The lifetime of bubbles, from formation to rupture, attracts attention because bubbles are often present in natural and industrial processes, and their geometry, drainage, coarsening, and rupture strongly affect those operations. Bubble rupture happens rapidly, and it may generate a cascade of small droplets or bubbles. Once a hole is nucleated within a bubble, it opens up with a variety of shapes and velocities depending on the liquid properties. A range of bubble rupture modes are reported in literature in which the reduction of a surface energy drives the rupture against inertial and viscous forces. The role of surface viscoelasticity of the liquid film in this colorful scenario is, however, still unknown. We found that the presence of interfacial viscoelasticity has a profound effect in the bubble bursting dynamics. Indeed, we observed different bubble bursting mechanisms upon the transition from viscous-controlled to surface viscoelasticity-controlled rupture. When this transition occurs, a bursting bubble resembling the blooming of a flower is observed. A simple modeling argument is proposed, leading to the prediction of the characteristic length scales and the number and shape of the bubble flower petals, thus paving the way for the control of liquid formulations with surface viscoelasticity as a key ingredient. These findings can have important implications in the study of bubble dynamics, with consequences for the numerous processes involving bubble rupture. Bubble flowering can indeed impact phenomena such as the spreading of nutrients in nature or the life of cells in bioreactors.


Assuntos
Simulação por Computador , Substâncias Viscoelásticas/química , Humanos , Propriedades de Superfície , Tensoativos
8.
Mol Pharm ; 18(4): 1656-1665, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33656340

RESUMO

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.


Assuntos
Anticorpos Monoclonais/química , Excipientes/química , Óleos de Silicone/química , Água/química , Adsorção , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Poloxâmero/química , Polissorbatos/química , Agregados Proteicos , Reologia , Tensão Superficial
9.
Pharm Res ; 38(3): 531-548, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33713012

RESUMO

PURPOSE: Enzymatic polysorbate (PS) degradation and resulting free fatty acid (FFA) particles are detrimental to biopharmaceutical drug product (DP) stability. Different types and grades of polysorbate have varying propensity to form FFA particles. This work evaluates the homogenous all-oleate (AO) PS80 alongside heterogeneous PS20 and PS80 grades in terms its propensity to form FFA particles and other important attributes like interfacial protection and oxidation susceptibility. METHODS: FFA particle formation rates were compared by degrading PS using non-immobilized hydrolases and fast degrading DP formulations. Interfacial protection of monoclonal antibodies (mAbs) was assessed by agitation studies in saline using non-degraded and degraded PS. Several antioxidants were assessed for their ability to mitigate AO PS80 oxidation and subsequent mAb oxidation by a 40°C placebo stability study and a 2, 2'-Azobis (2-amidinopropane) dihydrochloride stress model, respectively. RESULTS: Visible and subvisible particles were significantly delayed in AO PS80 formulations compared with heterogeneous PS20 and PS80 formulations. Non-degraded AO PS80 was less protective of mAbs against the air-water interface compared with heterogeneous PS20. Interfacial protection by AO PS80 improved upon degradation owing to high surface activity of FFAs. Diethylenetriaminepentaacetic acid (DTPA) completely mitigated AO PS80 oxidation unlike L-methionine and N-Acetyl-DL-Tryptophan. However, DTPA did not mitigate radical mediated mAb oxidation. CONCLUSION: AO PS80 is a promising alternative to reduce FFA particle formation compared with other PS types and grades. However, limitations observed here---such as lower protection against interfacial stresses and higher propensity for oxidation---need to be considered in assessing the risk/benefit ratio in using AO PS80.


Assuntos
Anticorpos Monoclonais/química , Portadores de Fármacos/química , Ácidos Graxos não Esterificados/química , Ácido Oleico/química , Polissorbatos/química , Composição de Medicamentos , Estabilidade de Medicamentos , Hidrólise , Metionina/química , Oxirredução , Estresse Oxidativo , Tamanho da Partícula , Triptofano/análogos & derivados , Triptofano/química
10.
J Pharm Sci ; 110(4): 1687-1692, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33141046

RESUMO

The use of monoclonal antibodies (mAbs) for the treatment of a variety of diseases is rapidly growing each year. Many mAbs are administered intravenously using i.v. bags containing 0.9% NaCl (normal saline). We studied the aggregation propensity of these antibody solutions in saline and compared it with a low ionic strength formulation buffer. The mAb studied in this work is prone to aggregate, and is known to form a viscoelastic network at the air-solution interface. We observed that this interfacial elasticity increased when formulated in saline. In the bulk, the mAbs exhibited a tendency to self-associate that was higher in saline. We also studied the aggregation of the mAbs in the presence of polysorbate-20, typically added to formulations to mitigate interfacial aggregation. We observed that with surfactants, the presence of salt in the buffer led to a greater mAb adsorption at the interface and resulted in the formation of more particulate aggregates. Our results show that the addition of salt to the buffer led to differences in the interfacial aggregation in mAb formulations, showing that stress studies used to screen for mAb aggregation intended for i.v. administration should be performed in conditions representative of their intended route of administration.


Assuntos
Anticorpos Monoclonais , Solução Salina , Adsorção , Polissorbatos , Tensoativos
11.
Colloids Surf B Biointerfaces ; 195: 111257, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32712549

RESUMO

The wetting and adsorption properties for two glycoproteins, recombinant human lubricin and bovine submaxillary mucins (BSM) were evaluated on hydrophilic and hydrophobic glass dome surfaces in a simplified in vitro tear film model. We show that both recombinant human lubricin (rh-lubricin) and BSM solutions render surfaces hydrophilic and when the fluid films reach 500 nm or less, the fluids resist evaporation-driven breakup through a volumetric flux across the surface, which we believe is due to evaporation-driven solutocapillary flows. rh-Lubricin was able to maintain a wet film without spontaneous breakup for longer periods of time than BSM at lower concentrations, which we attribute to differences in adsorption properties, measured by QCM-D, that result from surface charge and structural differences (confirmed by zeta potential, DLS, and SAXS measurements).


Assuntos
Mucinas , Adsorção , Animais , Bovinos , Glicoproteínas , Humanos , Espalhamento a Baixo Ângulo , Propriedades de Superfície , Difração de Raios X
12.
J Colloid Interface Sci ; 576: 252-263, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32422449

RESUMO

HYPOTHESIS: The properties of oil-in-water emulsions are influenced by the rheology of the aqueous phase (continuous phase) and the rheology of the oil-water interfaces. The bulk and interfacial rheological parameters can be tuned by incorporating nanoparticles (NPs) featuring different surface chemistries and polymers with different chemical or physical structures. Therefore, NPs and polymers can be used to formulate emulsions with different properties. EXPERIMENTS: The viscoelasticity at the oil-(aqueous phase) interface and the bulk viscoelasticity of aqueous phase were investigated in the presence of different fumed silica NPs (i.e., hydrophilic, hydrophobic, and slightly hydrophobic) and polymers with two different molecular weights. Bulk and interfacial viscoelastic properties were investigated, employing oscillatory rheological techniques. Furthermore, morphology and stability of the oil-in-(aqueous nanofluid) emulsions were explored utilizing bulk emulsification and single drop coalescence experiments. FINDINGS: Introducing polymers into the aqueous nanofluids had opposite effects on bulk and interfacial viscoelasticity. Despite the significant increase in bulk viscoelasticity upon addition of polymers into the aqueous nanofluids, the interfacial viscoelasticity and emulsion stability considerably decreased. The slightly hydrophobic NP nanofluids without polymers showed no bulk viscoelasticity, but displayed the highest interfacial viscoelasticity and emulsion stability. This provided us a unique opportunity to unravel the importance of bulk and interfacial viscoelasticity on oil-in-water emulsification and proved the dominant role of interfacial viscoelasticity over bulk viscoelasticity on emulsion stability.

13.
Soft Matter ; 16(21): 5094, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32432604

RESUMO

Correction for 'Viscoelastic interfaces comprising of cellulose nanocrystals and lauroyl ethyl arginate for enhanced foam stability' by Agnieszka Czakaj et al., Soft Matter, 2020, 16, 3981-3990, DOI: .

14.
J Colloid Interface Sci ; 575: 298-305, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32387738

RESUMO

The dynamics of air bubbles spreading on the underside of solid substrates is an important scientific problem with numerous applications. This work explores the spreading of bubbles against an ultra-thin, porous ultra-high-molecular-weight polyethylene (UHMWPE) film. This polymer film can be used in applications where a solid-liquid-gas interface is involved, like froth flotation for mineral processing, underwater methane capture, to prevent foaming in bioreactors, and in degassing in microfluidics. When an air bubble is released underneath such a film, the bubble bounces against the film, makes contact after the liquid film dewets, spreads against the film and shrinks in size as the gas within the bubble permeates through the pores of the film. In our work, these events were recorded using a high-speed camera. The effect of different surface-active species like surfactants, which exhibit interfacial mobility and proteins, which form a viscoelastic interfacial network, was also studied. The adsorption of these surface-active molecules led to profound differences in the interaction of the bubbles and their ultimate removal through the film. Importantly, the permeation flux of the bubbles was lower in the presence of these molecules, affected in part by a lower capillary driving force and also because of the decreased film permeability. This ultra-thin film offers a high permeation flux, which makes it a promising candidate for the aforementioned applications. Furthermore, the effect of surface-active species such as surfactants and proteins encountered in these environments is elucidated.

15.
Soft Matter ; 16(16): 3981-3990, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32250379

RESUMO

Stable aqueous foams composed of oppositely charged nanoparticles and surfactants have recently gained attention. We studied the draining of thin liquid films and the foam stability of aqueous mixtures of food grade cellulose nanocrystals (CNCs) and an oppositely charged surfactant - lauroyl ethyl arginate (LAE). Dynamic fluid film interferometry experiments with the bubble approaching the air/solution interface revealed a two-fold increase of the initial bubble film thickness and a maximum in drainage time at the optimal stoichiometry of LAE and CNC. The temporal evolution of the fluid film shape indicated a large contribution of structural forces to the film stability. The results of single liquid film drainage time and coalescence time experiments were partially correlated with bulk foam stability. With a further increase of LAE concentration, aggregation-induced foam destruction was observed. In the presence of a cationic surfactant, anisotropic and initially hydrophilic cellulose nanocrystals became partially hydrophobized and self-assembled at the interface. Cellulose nanocrystal shape anisotropy and wetting behaviour which have their origins in OH-exposed and buried crystalline planes are the sources of capillary interactions that promote CNC aggregation at planar and curved liquid/air interfaces. Dilatational and shear interfacial rheology experiments confirmed the formation of a highly elastic surfactant-nanoparticle interfacial layer. To the best of our knowledge, this is the first report on foaming properties for this system with fast adsorption kinetics influenced by CNC.

16.
J Colloid Interface Sci ; 550: 128-138, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31055138

RESUMO

Monoclonal antibodies (mAbs) are therapeutic proteins used in the treatment of many diseases due to their specificity in binding targets. Aggregation of these molecules is a major challenge in their formulation development. MAbs spontaneously adsorb onto air-solution interfaces and experience interfacial stresses, which is one of the major causes of aggregation. This work studies the effect of pharmaceutically relevant surfactants like polysorbate-20, poloxamer-188 and polyethylene glycol in controlling the aggregation and interfacial behavior of a mAb prone to interfacial aggregation. Agitation-induced aggregation was characterized using size-exclusion chromatography, flow cytometry and light obscuration. The addition of surfactants reduced the formation of aggregates. In the presence of surfactants competitively adsorbing to the interface, the number of soluble aggregates (size < 100 nm) depended on the amount of mAb adsorbed. On the other hand, the number of insoluble aggregates was governed not by the surface concentration, but by the ability of the adsorbed mAbs to interact and form a cohesive network. To correlate the aggregation in these mAb-surfactant mixtures with their interfacial behavior, studies on the drainage of a fluid film sandwiched between two mAb-surfactant laden interfaces were performed. The amount of fluid entrained depended on different governing mechanisms - interfacial rheology, surface tension and surface tension gradients for different surfactants. The surface tension gradients further resulted in an instability and local thickening in the sandwiched fluid film, which was affected by the presence of mAbs. Understanding the aggregation propensities of different mAb-surfactant mixtures and linking them to the interfacial behavior will greatly aid in understanding the aggregation mechanism and in mitigating aggregate formation by optimizing surfactant type and concentration in the formulation.


Assuntos
Anticorpos Monoclonais/química , Agregados Proteicos/efeitos dos fármacos , Tensoativos/química , Adsorção , Animais , Linhagem Celular , Cricetulus , Composição de Medicamentos/métodos , Feminino , Ovário/citologia , Tamanho da Partícula , Reologia/métodos , Propriedades de Superfície , Tensão Superficial , Viscosidade , Água/química
17.
Langmuir ; 34(2): 630-638, 2018 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-29251942

RESUMO

Monoclonal antibodies (mAbs) are proteins that uniquely identify targets within the body, making them well-suited for therapeutic applications. However, these amphiphilic molecules readily adsorb onto air-solution interfaces where they tend to aggregate. We investigated two mAbs with different propensities to aggregate at air-solution interfaces. The understanding of the interfacial rheological behavior of the two mAbs is crucial in determining their aggregation tendency. In this work, we performed interfacial stress relaxation studies under compressive step strain using a custom-built dilatational rheometer. The dilatational relaxation modulus was determined for these viscoelastic interfaces. The initial value and the equilibrated value of relaxation modulus were larger in magnitude for the mAb with a higher tendency to aggregate in response to interfacial stress. We also performed single-bubble coalescence experiments using a custom-built dynamic fluid-film interferometer (DFI). The bubble coalescence times also correlated to the mAbs aggregation propensity and interfacial viscoelasticity. To study the influence of surfactants in mAb formulations, polyethylene glycol (PEG) was chosen as a model surfactant. In the mixed mAb/PEG system, we observed that the higher aggregating mAb coadsorbed with PEG and formed domains at the interface. In contrast, for the other mAb, PEG entirely covered the interface at the concentrations studied. We studied the mobility of the interfaces, which was manifested by the presence or the lack of Marangoni stresses. These dynamics were strongly correlated with the interfacial viscoelasticity of the mAbs. The influence of competitive destabilization in affecting the bubble coalescence times for the mixed mAb/PEG systems was also studied.

18.
Sci Rep ; 5: 10522, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-26041686

RESUMO

The discovery of graphene has led to a rising interest in seeking quasi two-dimensional allotropes of several elements and inorganic compounds. Boron, carbon's neighbour in the periodic table, presents a curious case in its ability to be structured as graphene. Although it cannot independently constitute a honeycomb planar structure, it forms a graphenic arrangement in association with electron-donor elements. This is exemplified in magnesium diboride (MgB2): an inorganic layered compound comprising boron honeycomb planes alternated by Mg atoms. Till date, MgB2 has been primarily researched for its superconducting properties; it hasn't been explored for the possibility of its exfoliation. Here we show that ultrasonication of MgB2 in water results in its exfoliation to yield few-layer-thick Mg-deficient hydroxyl-functionalized nanosheets. The hydroxyl groups enable an electrostatically stabilized aqueous dispersion and create a heterogeneity leading to an excitation wavelength dependent photoluminescence. These chemically modified MgB2 nanosheets exhibit an extremely small absorption coefficient of 2.9 ml mg(-1) cm(-1) compared to graphene and its analogs. This ability to exfoliate MgB2 to yield nanosheets with a chemically modified lattice and properties distinct from the parent material presents a fundamentally new perspective to the science of MgB2 and forms a first foundational step towards exfoliating metal borides.

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