Physical Stability of Albinterferon-α2b in Aqueous Solution: Effects of Conformational Stability and Colloidal Stability on Aggregation

2012 ◽  
Vol 101 (8) ◽  
pp. 2702-2719 ◽  
Author(s):  
Danny K. Chou ◽  
Rajesh Krishnamurthy ◽  
Mark Cornell Manning ◽  
Theodore W. Randolph ◽  
John F. Carpenter
Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1646
Author(s):  
Jordan Bye ◽  
Kiah Murray ◽  
Robin Curtis

A common strategy to increase aggregation resistance is through rational mutagenesis to supercharge proteins, which leads to high colloidal stability, but often has the undesirable effect of lowering conformational stability. We show this trade-off can be overcome by using small multivalent polyphosphate ions, adenosine triphosphate (ATP) and tripolyphosphate (TPP) as excipients. These ions are equally effective at suppressing aggregation of ovalbumin and bovine serum albumin (BSA) upon thermal stress as monitored by dynamic and static light scattering. Monomer loss kinetic studies, combined with measurements of native state protein–protein interactions and ζ-potentials, indicate the ions reduce aggregate growth by increasing the protein colloidal stability through binding and overcharging the protein. Out of three additional proteins studied, ribonuclease A (RNaseA), α-chymotrypsinogen (α-Cgn), and lysozyme, we only observed a reduction in aggregate growth for RNaseA, although overcharging by the poly-phosphate ions still occurs for lysozyme and α-Cgn. Because the salts do not alter protein conformational stability, using them as excipients could be a promising strategy for stabilizing biopharmaceuticals once the protein structural factors that determine whether multivalent ion binding will increase colloidal stability are better elucidated. Our findings also have biological implications. Recently, it has been proposed that ATP also plays an important role in maintaining intracellular biological condensates and preventing protein aggregation in densely packed cellular environments. We expect electrostatic interactions are a significant factor in determining the stabilizing ability of ATP towards maintaining proteins in non-dispersed states in vivo.


2021 ◽  
Vol 8 (2) ◽  
pp. 40-49
Author(s):  
Nazir Kizzie-Hayford ◽  
Jerry Ampofo-Asiama ◽  
Susann Zahn ◽  
Doris Jaros ◽  
Harald Rohm

Tiger nut milk (TNM) shows limited colloidal stability, which affects consumer acceptability in many parts of the world where tiger nut is cultivated. In this study, addition of proteins and hydrocolloids was used for improving the stability, and the impact on physical properties and consumer acceptance is reported. Enriching TNM by 3 g/100 g sodium caseinate and 0.1 g/100 g xanthan gum successfully impeded creaming and serum formation and resulted in a decrease of the instability index from 0.408 ± 0.023 to 0.015 ± 0.00 after applying forced sedimentation at 3000 x g for 2 h. After TNM enrichment, the viscosity of TNM increased from 3.0 ± 0.10 mPa.s to 285 ± 18 mPa.s which remained stable at elevated storage temperature. Flash profiling of TNM resulted in emerging descriptors namely sweet, sediment, watery, raw. Hedonic assessment by 82 consumers showed that plain TNM had the lowest rating concerning particular sensory attributes and acceptance. Enrichment resulted in more viscous, sweet and thick TNM products, leading to higher consumer ratings of attributes and acceptability. Thus, enriching TNM by sodium caseinates and xanthan gum is promising for improving the dispersion stability and consumer acceptance.


2019 ◽  
Vol 58 (11) ◽  
pp. 4479-4486 ◽  
Author(s):  
Taiheng Yin ◽  
Zihao Yang ◽  
Meiqin Lin ◽  
Juan Zhang ◽  
Zhaoxia Dong

2015 ◽  
Vol 4 (2) ◽  
Author(s):  
Neus Bernat ◽  
Maite Cháfer ◽  
Amparo Chiralt ◽  
Chelo González-Martínez

Probiotics in almond-based matrices were considered as a means of obtaining fermented products which would cover both the current demand for health-promoting foods and for alternatives to standard yoghurts. Firstly, the combined effect of high pressure homogenisation (HPH) and heat treatment on the physical stability of almond “milk” was studied. The beverage was homogenised by applying 62, 103 and 172 MPa (MF1, MF2 and MF3 respectively); MF3 was also combined with two different heat treatments (85 ºC-30 min (LH) and 121 ºC-15 min (HH)). Both microstructure and colloidal stability were analysed in all the processed samples to select the most suitable treatment with which to obtain a stable product. The selected almond milk was then fermented with probiotic Lactobacillus reuteri and Streptococcus thermophilus and the final product was characterised throughout cold storage time (28 days) as to pH, acidity, serum retention and starter viability. A sensory evaluation and probiotic survival to in vitro digestion was also conducted. The results showed that the physical and structural almond-milk properties were affected by both HPH and heat treatments, obtaining the greatest stability in MF3-LH samples. The fermented milk permitted probiotic survivals above the level suggested as minimum for ensuring health benefits during the entire controlled time and, hence, can be considered as a functional food. No differences in the sensory acceptability of the product were found between 1 and 28 storage days. Therefore, a new, functional, fermented product was developed, which was suitable for targeted groups, such as the lactose-intolerant and cow-milk-protein allergic populations.


2016 ◽  
Vol 21 (8) ◽  
pp. 842-850 ◽  
Author(s):  
Jensen J. H. Wong ◽  
Sara K. Wright ◽  
Irene Ghozalli ◽  
Rajni Mehra ◽  
Kenji Furuya ◽  
...  

Technologies to improve the throughput for screening protein formulations are continuously evolving. The purpose of this article is to highlight novel applications of a molecular rotor dye, 4-(4-(dimethylamino)styryl)- N-methylpyridinium iodide (DASPMI) in screening for the conformational stability, colloidal stability, and subtle pretransition dynamics of protein structures during early formulation development. The measurement of the apparent unfolding temperature (Tm) for a monoclonal antibody in the presence of Tween 80 was conducted and data were compared to the results of differential scanning calorimetry (DSC) measurements. Additionally, measuring the fluorescence intensity of DASPMI as a function of protein concentration shows consistent correlation to the diffusion interaction parameter (kD) for two distinct monoclonal antibody formulations measured by DLS. Lastly, due to the sensitivity of the molecular rotor dye to changes in microviscosity (ηmicro), subtle pretransition dynamics were discernable for two monoclonal antibody formulations that correlate with findings by red-edge excitation shift (REES) experiments. This novel application of molecular rotor dyes offers a valuable and promising approach for streamlining the early formulation development process due to low material consumption and rapid analysis time in a 96-well plate format.


2003 ◽  
Vol 12 (5) ◽  
pp. 903-913 ◽  
Author(s):  
Eva Y. Chi ◽  
Sampathkumar Krishnan ◽  
Brent S. Kendrick ◽  
Byeong S. Chang ◽  
John F. Carpenter ◽  
...  

Polymers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1627 ◽  
Author(s):  
Jun Zhong ◽  
Ranjith Kumar Kankala ◽  
Shi-Bin Wang ◽  
Ai-Zheng Chen

Recently, metal-organic frameworks (MOFs) have garnered enormous attention from researchers owing to their superior physicochemical properties, which are of particular interest in various fields such as catalysis and the diverse areas of biomedicine. Despite their position in the utilization for various applications compared to other innovative nanocarriers such as dendrimers and mesoporous silica nanoparticles (MSNs), in terms of advantageous physicochemical attributes, as well as attractive textural properties, ease of characterization, and abundant surface chemistry for functionalization and other benefits, MOFs yet suffer from several issues such as poor degradability, which might lead to accumulation-induced biocompatibility risk. In addition, some of the MOFs suffer from a shortcoming of poor colloidal stability in the aqueous solution, hindering their applicability in diverse biomedical fields. To address these limitations, several advancements have been made to fabricate polymeric nanocomposites of MOFs for their utility in various biomedical fields. In this review, we aim to provide a brief emphasis on various organic polymers used for coating over MOFs to improve their physicochemical attributes considering a series of recently reported intriguing studies. Finally, we summarize with perspectives.


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