What’s new in the controversy on the renal/tissue toxicity of starch solutions?

Lameire, Norbert; Hoste, Eric

doi:10.1007/s00134-013-3191-6

Cited by 6 publications

(6 citation statements)

References 14 publications

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“…While HES was commonly used as a volume expander for patients with severe blood loss, currently the safety of HES is under controversy. On the scale used for fluid therapy, HES has been shown to accumulate in the liver, kidney, and bone marrow, leading to increased risk of kidney injury and death for critically ill patients . While HESylated proteins exhibit good pharmacokinetic properties, the side effects associated with the repeated use of HES may be a hindrance to their adoption as conjugates for all patient populations.…”

Section: Alternatives To Peg In Developmentmentioning

confidence: 99%

Therapeutic Protein–Polymer Conjugates: Advancing Beyond PEGylation

2014

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Protein-polymer conjugates are widely used as therapeutics. All Food and Drug Administration (FDA)-approved protein conjugates are covalently linked to poly(ethylene glycol) (PEG). These PEGylated drugs have longer half-lives in the bloodstream, leading to less frequent dosing, which is a significant advantage for patients. However, there are some potential drawbacks to PEG that are driving the development of alternatives. Polymers that display enhanced pharmacokinetic properties along with additional advantages such as improved stability or degradability will be important to advance the field of protein therapeutics. This perspective presents a summary of protein-PEG conjugates for therapeutic use and alternative technologies in various stages of development as well as suggestions for future directions. Established methods of producing protein-PEG conjugates and new approaches utilizing controlled radical polymerization are also covered.

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Section: Alternatives To Peg In Developmentmentioning

confidence: 99%

Therapeutic Protein–Polymer Conjugates: Advancing Beyond PEGylation

2014

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“…For instance, hydroxyethyl starch has been extensively used for the preparation of protein conjugates with increased half-lives, but may accumulate in some organs increasing risk of death for critically ill patients. [18,19] To address this need, we recently described stabilizing polymers with polyester backbones. [17] Specifically, polycaprolactone was prepared with zwitterionic and trehalose side chains.…”

Section: Doi: 101002/marc201700652mentioning

confidence: 99%

“…Hydrolytically or enzymatically degradable alternatives have been used, but some present problems such as undesired biological side effects or difficulty in attaching protein‐reactive units. For instance, hydroxyethyl starch has been extensively used for the preparation of protein conjugates with increased half‐lives, but may accumulate in some organs increasing risk of death for critically ill patients . To address this need, we recently described stabilizing polymers with polyester backbones .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of a Degradable Trehalose Glycopolymer Prepared by RAFT Polymerization

Lau

Pelegri-O’Day

Maynard

2017

Macromol. Rapid Commun.

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There is a significant need for new biodegradable protein stabilizing polymers. Herein, the synthesis of a polymer with trehalose side chains and hydrolytically degradable backbone esters and its evaluation for protein stabilization and cytotoxicity are described. Specifically, an alkene-containing parent polymer is synthesized by reversible addition-fragmentation chain transfer polymerization, and thiolated trehalose is installed using a radical-initiated thiol-ene reaction. The stabilizing properties of the polymer are investigated by thermally stressing granulocyte colony-stimulating factor (G-CSF), which is expressed and purified using a custom-designed G-CSF fusion protein with a polyhistidine-tagged maltose binding protein. The degradable polymer is shown to stabilize G-CSF to 66% after heating at 40 °C. Poly(5,6-benzo-2-methylene-1,3-dioxepane (BMDO)-co-butyl methacrylate-trehalose) is degraded and its cellular compatibility is investigated. While the polymer is noncytotoxic, cytotoxic effects are observed from the degraded products in fibroblasts and murine myeloblasts. These data provide important information for future use of BMDO-containing trehalose glycopolymers for biomedical applications.

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“…Colloids, at least theoretically, should enable faster and more effective intravascular volume expansion than colloids, with less risk of volume overload as long as the glycocalix is not significantly damaged. Thus, in early volume resuscitation and hemodynamic instability which is not sufficiently treatable with crystalloids, colloids may be the only alternative to stabilize patients [ 61 ].…”

Section: Acute Kidney Injurymentioning

confidence: 99%