N-terminal PEGylation of human serum albumin and investigation of its pharmacokinetics and pulmonary microvascular retention

Zhao, Xiujian

doi:10.5582/bst.2012.v6.2.81

Cited by 10 publications

(11 citation statements)

References 31 publications

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“…PEG-INTRON® (Sylatron TM ), PEGASYS®, Mircera® are also examples of randomly PEGylated drugs (Table I), but in this case they are mixtures of mono-PEGylated positional isomers exhibiting extended half-lifes in comparison to the originator drugs. PEGylation reactions can be directed towards the formation of site-specific PEGylated conjugates by the optimization of reaction conditions (Veronese, 2001;Zhao et al, 2012;Da Silva Freitas, Mero, Pasut, 2013). An example of a site-specific PEGylated biobetter available in the market is Neulasta® (Table I), an N-terminally mono-PEGylated granulocytecolony stimulating factor (G-CSF).…”

Section: Pegylation Reaction Designmentioning

confidence: 99%

“…As mentioned above, most part of the purification processes for PEGylated proteins are based on chromatographic techniques, especially size exclusion chromatography (SEC) (Maiser et al, 2015) and ion exchange chromatography (IEX) (Zhao et al, 2012). SEC is a chromatographic method in which molecules in solution are separated by molecular weight (MW).…”

Section: Chromatographic Fractionation Platformsmentioning

confidence: 99%

“…The best protocol must be achieved case-by-case depending on the specific protein and type of PEGylation (Fee, Van Alstine, 2011). In the recent years, IEX has been the most used downstream technique for the separation of PEGylated conjugates ( Figure 10) (Abe et al, 2010;Moosmann et al, 2012;Zhao et al, 2012;Morgenstern et al, 2017). The major challenge of IEX refers to the fact that PEG chains sterically interfere in the interaction of the protein charged residues and the ionic exchange support, producing a masking effect of the charges (Fee, Van Alstine, 2011).…”

Section: Chromatographic Fractionation Platformsmentioning

confidence: 99%

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Protein PEGylation for the design of biobetters: from reaction to purification processes

Santos

Torres-Obreque

Meneguetti

et al. 2018

Braz. J. Pharm. Sci.

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The covalent attachment of polyethylene glycol (PEG) to therapeutical proteins is an important route to develop biobetters for biomedical, biotech and pharmaceutical industries. PEG conjugation can shield antigenic epitopes of the protein, reduce degradation by proteolytic enzymes, enhance long-term stability and maintain or even improve pharmacokinetic and pharmacodynamics characteristics of the protein drug. Nonetheless, correct information in terms of the PEGylation process from reaction to downstream processing is of paramount importance for the industrial application and processing scale-up. In this review we present and discuss the main steps in protein PEGylation, namely: PEGylation reaction, separation of the products and final characterization of structure and activity of the resulting species. These steps are not trivial tasks, reason why bioprocessing operations based on PEGylated proteins relies on the use of analytical tools according to the specific pharmaceutical conjugate that is being developed. Therefore, the appropriate selection of the technical and analytical methods may ensure success in implementing a feasible industrial process.

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Section: Pegylation Reaction Designmentioning

confidence: 99%

Section: Chromatographic Fractionation Platformsmentioning

confidence: 99%

Section: Chromatographic Fractionation Platformsmentioning

confidence: 99%

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Protein PEGylation for the design of biobetters: from reaction to purification processes

Santos

Torres-Obreque

Meneguetti

et al. 2018

Braz. J. Pharm. Sci.

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“…Covalently attaching PEG chains to the peptide improves enzymatic stability because of steric hindrance of proteolytic enzymes. This suppressed the immune response [132][133][134]. PEGylation has been shown to induce vacuolisation (formation of vacuoles within/adjacent to cells), but current research has focused on limiting this effect by using different carriers or shortening chain lengths [135][136][137].…”

Section: Therapeutic Applications Of Pyy Peptidesmentioning

confidence: 99%

Peptide hormones and lipopeptides: from self‐assembly to therapeutic applications

Hutchinson

Burholt

Hamley

2017

Journal of Peptide Science

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This review describes the properties and activities of lipopeptides and peptide hormones and how the lipidation of peptide hormones could potentially produce therapeutic agents combating some of the most prevalent diseases and conditions. The self‐assembly of these types of molecules is outlined, and how this can impact on bioactivity. Peptide hormones specific to the uptake of food and produced in the gastrointestinal tract are discussed in detail. The advantages of lipidated peptide hormones over natural peptide hormones are summarised, in terms of stability and renal clearance, with potential application as therapeutic agents. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

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“…Although not a conventional HBOC, SANGUINATE is designed to address these issues through the use of PEGylation [8,9] and carboxylation [10]. The modification of Hb with polyethylene glycol increases the effective molecular size, thereby preventing extravasation and the scavenging of NO.…”

Section: Introductionmentioning

confidence: 99%

Toxicology and Safety Determination for a Novel Therapeutic Dual Carbon Monoxide and Oxygen Delivery Agent

Newmark¹

2014

J Clin Toxicol

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Conditions in patients with hemoglobinopathies are far more complex and variable than in healthy humans due to the cascade of injury from hypoxia. Resulting complications can lead to tissue death, organ dysfunction and even death. Multi-faceted treatment is needed to address the array of complications. SANGUINATE ™ (PEGylated, bovine carboxyhemoglobin) has multiple mechanisms of action that may prove effective. It acts both as a carbon monoxidereleasing molecule and as an oxygen transfer agent and is designed to safely perfuse the microvasculature to oxygenate tissue. Designing toxicology studies must not only deal with ensuring the safety of its mechanisms but deal with the potential safety issues of using bovine hemoglobin for both acute and chronic administration. Similar products have previously been shown to have effects on inflammation, vasoactivity, cardiac toxicity and nephrotoxicity as well as pro-coagulant activity. Therefore, studies were designed to thoroughly address the potential of these effects in conjunction with the traditional toxicology and safety pharmacology studies.These toxicology and safety studies were designed to address the FDA's particular concerns of this novel drug candidate. There were several unique features to this preclinical program including a renal functional study, immunohistochemical and special staining of tissues, measurement of hemoglobin in the urine, measurement of troponin in the serum, inclusion of high dose/high volume groups, and analysis of interference for clinical pathology parameters. To address toxicity and safety concerns of its use as a single or repeating dose therapeutic, SANGUINATE was tested in pivotal studies using three species in repeating doses. There were no adverse effects identified for any doses and therefore, a no observed adverse effect level (NOAEL) was not determined even at dosage levels of 1200 mg/kg (monkey), 1600 mg/kg (pig) and 2400 mg/kg (rat). The completion of these studies permitted SANGUINATE to move into clinical trials.

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N-terminal PEGylation of human serum albumin and investigation of its pharmacokinetics and pulmonary microvascular retention

Cited by 10 publications

References 31 publications

Protein PEGylation for the design of biobetters: from reaction to purification processes

Protein PEGylation for the design of biobetters: from reaction to purification processes

Peptide hormones and lipopeptides: from self‐assembly to therapeutic applications

Toxicology and Safety Determination for a Novel Therapeutic Dual Carbon Monoxide and Oxygen Delivery Agent

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