Effects of Excipient Interactions on the State of the Freeze-Concentrate and Protein Stability

Jena, Sampreeti; Horn, Jacqueline; Suryanarayanan, Raj; Frieß, Wolfgang; Aksan, Alptekin

doi:10.1007/s11095-016-2078-y

Cited by 31 publications

(18 citation statements)

References 92 publications

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“…64,65 More recent studies show that low concentrations may be necessary and even beneficial, 66,67 with interesting recent hypotheses on the use of heavy isotopes for increasing human longevity. 68 Finally, there is some interest in the use of D 2 O as an excipient 52,69 because of the observation that D 2 O can stabilize vaccines. 70 Understanding the effects of isotopic waters is key to understanding biology, including protein folding.…”

Section: O Affects Many Biological Processesmentioning

confidence: 99%

Enthalpic stabilization of an SH3 domain by D₂O

Stadmiller

Pielak

2018

Protein Science

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The stability of a protein is vital for its biological function, and proper folding is partially driven by intermolecular interactions between protein and water. In many studies, H O is replaced by D O because H O interferes with the protein signal. Even this small perturbation, however, affects protein stability. Studies in isotopic waters also might provide insight into the role of solvation and hydrogen bonding in protein folding. Here, we report a complete thermodynamic analysis of the reversible, two-state, thermal unfolding of the metastable, 7-kDa N-terminal src-homology 3 domain of the Drosophila signal transduction protein drk in H O and D O using one-dimensional F NMR spectroscopy. The stabilizing effect of D O compared with H O is enthalpic and has a small to insignificant effect on the temperature of maximum stability, the entropy, and the heat capacity of unfolding. We also provide a concise summary of the literature about the effects of D O on protein stability and integrate our results into this body of data.

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Section: O Affects Many Biological Processesmentioning

confidence: 99%

Enthalpic stabilization of an SH3 domain by D₂O

Stadmiller

Pielak

2018

Protein Science

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“…Unfortunately, due to the structural flexibility and susceptibility to environmental stressors, the increasing use of therapeutic proteins also poses an important challenge related to their instability, which not only leads to decreased bioactivity, but may also potentially elicit undesired immunological responses . At present, lyophilization or freeze‐drying is the most widely used approach to stabilize these proteins, although elevated temperature and moisture (even trace amount) still need to be avoided during protein storage in dry state . Apart from solid forms, a large portion of therapeutic proteins today is formulated as aqueous solutions in a ready‐to‐use form, especially for patients in resource‐limited settings and requiring rapid administration.…”

Section: Introductionmentioning

confidence: 99%

Metal‐Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics

Wang

Sudlow

Wang

et al. 2018

Adv Healthcare Materials

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Protein therapeutics are prone to lose their structure and bioactivity under various environmental stressors. Herein, we report a facile approach using a nanoporous material, zeolitic imidazolate framework-8 (ZIF-8), as an encapsulant for preserving the prototypic protein therapeutic, insulin, against different harsh conditions that may be encountered during storage, formulation and transport, including elevated temperatures, mechanical agitation and organic solvent. Both immunoassay and spectroscopy analysis demonstrate the preserved chemical stability and structural integrity of insulin offered by the ZIF-8 encapsulation. Biological activity of ZIF-8 preserved insulin after storage under accelerated degradation conditions (i.e. 40°C) was evaluated in vivo using a diabetic mouse model, and showed comparable bioactivity to refrigeration-stored insulin (−20°C). We also demonstrate that ZIF-8 preserved insulin had low cytotoxicity in vitro and did not cause side effects in vivo. Furthermore, ZIF-8 residue can be completely removed by a simple purification step before insulin administration. This biopreservation approach is potentially applicable to diverse protein therapeutics, thus extending the benefits of advanced biologics to resource-limited settings and underserved populations/regions.

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“…4,7,9 A rapid heating rate is known to not only delay devitrication during warming but also reduces extent of recrystallization. 68 Thus, rapid warming produced the most pronounced effect in samples that were cooled below the glass transition temperature and vitried. Interestingly, thawing rate did not affect the tertiary structure of albumin at all (Table 4) indicating that tertiary unfolding of albumin occurred during the slow cooling stage itself.…”

Section: Resultsmentioning

confidence: 98%

Effect of high DMSO concentration on albumin during freezing and vitrification

Jena

Aksan

2017

RSC Adv.

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Effects of Excipient Interactions on the State of the Freeze-Concentrate and Protein Stability

Abstract: The API and other excipients, in a concentration-dependent manner, influenced the physical state of the freeze concentrate as well as the stability of the API.

Cited by 31 publications

References 92 publications

Enthalpic stabilization of an SH3 domain by D₂O

Enthalpic stabilization of an SH3 domain by D₂O

Metal‐Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics

Effect of high DMSO concentration on albumin during freezing and vitrification

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Effects of Excipient Interactions on the State of the Freeze-Concentrate and Protein Stability

Abstract: The API and other excipients, in a concentration-dependent manner, influenced the physical state of the freeze concentrate as well as the stability of the API.

Cited by 31 publications

References 92 publications

Enthalpic stabilization of an SH3 domain by D2O

Enthalpic stabilization of an SH3 domain by D2O

Metal‐Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics

Effect of high DMSO concentration on albumin during freezing and vitrification

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Product

Resources

About

Enthalpic stabilization of an SH3 domain by D₂O

Enthalpic stabilization of an SH3 domain by D₂O