Molecular origins of surfactant-mediated stabilization of protein drugs

Lee, Hyo Jin; McAuley, Arnold; Schilke, Karl F.; McGuire, Joseph

doi:10.1016/j.addr.2011.06.015

Cited by 199 publications

(174 citation statements)

References 60 publications

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“…They act as a protein stabilizer (usually small ions, low polarizability), and as polar water-structure makers Detergents: Surfactants can stabilize proteins by two major mechanisms: (a) by settling at an interface, and preventing protein adsorption and associated surface activity loss and/or surface-induced aggregation or (b) by binding to hydrophobic patches of proteins and thus preventing a close approach and aggregation. Some surfactants may function according to only one of these mechanisms, whereas others may function according to both [3] Ligands, inhibitors, etc. : Can stabilize the protein structure Aggregation destabilizing (Chaotropic) agents.…”

Section: Protein Environmentmentioning

confidence: 99%

Production of prone‐to‐aggregate proteins

Lebendiker¹,

Danieli²

2013

FEBS Letters

129

102

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a b s t r a c tExpression of recombinant proteins in Escherichia coli (E. coli) remains the most popular and costeffective method for producing proteins in basic research and for pharmaceutical applications. Despite accumulating experience and methodologies developed over the years, production of recombinant proteins prone to aggregate in E. coli-based systems poses a major challenge in most research applications. The challenge of manufacturing these proteins for pharmaceutical applications is even greater. This review will discuss effective methods to reduce and even prevent the formation of aggregates in the course of recombinant protein production. We will focus on important steps along the production path, which include cloning, expression, purification, concentration, and storage.

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Section: Protein Environmentmentioning

confidence: 99%

Production of prone‐to‐aggregate proteins

Lebendiker¹,

Danieli²

2013

FEBS Letters

129

102

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“…Figure 5 is a representation of the assumed filgrastim adsorption process on infusion sets. 26) Unlike sorption, drug adsorption to the infusion set surface is monomolecular adsorption. 27) Therefore, the adsorption no longer produces it if the infusion set surface is saturated with an adsorbed drug.…”

Section: Resultsmentioning

confidence: 99%

Comparison of the Adsorption of Original and Biosimilar Preparations of Filgrastim on Infusion Sets and the Inhibition of Adsorption by Polysorbate 80

Tange

Matsumoto

Yoshida

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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The purpose of the study was to evaluate the adsorption of filgrastim on infusion sets (comprising infusion bag, line and filter) and to compare the adsorption of the original filgrastim preparation with biosimilar preparations using HPLC. The inhibitory effect of polysorbate 80 on this adsorption was also evaluated. Filgrastim was mixed with isotonic sodium chloride solution or 5% (w/v) glucose solution in the infusion fluid. Filgrastim adsorption on infusion sets was observed with all preparations and with both types of infusion solution. The adsorption ratio was about 30% in all circumstances. Filgrastim adsorption on all parts of the infusion set (bag, line and filter) was dramatically decreased by the addition of polysorbate 80 solution at concentrations at or over its critical micelle concentration (CMC). The filgrastim adsorption ratio was highest at a solution pH of 5.65, which is the isoelectric point (pI) of filgrastim. This study showed that the degree of filgrastim adsorption on infusion sets is similar for original and biosimilar preparations, but that the addition of polysorbate 80 to the infusion solution at concentrations at or above its CMC is effective in preventing filgrastim adsorption. The addition of a total-vitamin preparation with a polysorbate 80 concentration over its CMC may be an effective way of preventing filgrastim adsorption on infusion sets. Key words filgrastim; adsorption; infusion set; polysorbate 80The Japanese government now actively promotes the use of generic drugs in order to reduce national medical expenditure.1) As part of the drive to reduce health costs, biosimilar preparations are also beginning to be used in clinical practice in place of original biologicals. However, there are growing concerns about switching from the original preparation to biosimilar preparations in clinical practice.2) In contrast to generic preparations, it is widely considered to be impossible to make biosimilar preparations with identical biophysical properties to the original preparations. The uptake of biosimilar preparations has not been as rapid as the change to generic preparations as switching to a biosimilar preparation does not result in as much cost savings as switching to a generic preparation, bio-pharmaceuticals also being covered by high-cost illness insurance.Filgrastim is a granulocyte colony-stimulating factor used to treat neutropenia. Generally, filgrastim is administered subcutaneously but in patients with a known bleeding disorder, intravenous infusions may be required. In previous reports, original and biosimilar preparations of filgrastim have been shown to have similar clinical effects. [3][4][5] In previous reports, it has been demonstrated that protein preparations, such as insulin, adsorb to infusion sets, 6-8) and filgrastim adsorption on infusion sets has also been reported.9-13) Thus, it is possible that the actual dose of filgrastim infused will be smaller than the theoretical dose predicted. Yagi and Kawa have also found that differences in flow rate affect the ...

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“…2 For example, the conventional surfactants used in protein formulations are typically small non-ionic surfactants that either occupy the interface by direct competition with the protein, form surfactant-protein complexes that are less surface-interactive and thus remain in solution, or a combination of both. 38 Non-ionic surfactants from the polysorbate class, such as PS80 (also known as Tween Ò 80), are common excipients used in formulations of therapeutic proteins. Typically, surfactants have been added to protect against mechanical stresses, namely freeze-thaw and shake.…”

Section: Discussionmentioning

confidence: 99%

Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

Morar-Mitrica

Puri

Sassi

et al. 2015

mAbs

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The physical and chemical integrity of a biopharmaceutical must be maintained not only during long-term storage but also during administration. Specifically for the intravenous (i.v.) delivery of a protein drug, loss of stability can occur when the protein formulation is compounded with i.v. bag diluents, thus modifying the original composition of the drug product. Here we present the challenges associated with the delivery of a low-dose, highly potent monoclonal antibody (mAb) via the i.v. route. Through parallel in-use stability studies and conventional formulation development, a drug product was developed in which adsorptive losses and critical oxidative degradation pathways were effectively controlled. This development approach enabled the i.v. administration of clinical doses in the range of 0.1 to 0.5 mg total protein, while ensuring liquid drug product storage stability under refrigerated conditions.

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Molecular origins of surfactant-mediated stabilization of protein drugs

Cited by 199 publications

References 60 publications

Production of prone‐to‐aggregate proteins

Production of prone‐to‐aggregate proteins

Comparison of the Adsorption of Original and Biosimilar Preparations of Filgrastim on Infusion Sets and the Inhibition of Adsorption by Polysorbate 80

Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

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