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over 5000 supplements on sale at professional muscle store
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over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store

PEGylation

ElvisTerence

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May 31, 2010
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Many biopharmaceuticals suffer from performance problems due to short half lives, immunogenicity, and poor solubility and stability. Clinically proven Advanced Pegylation, the technology of polyethylene glycol (PEG) conjugation, holds significant promise in maintaining effective plasma concentrations of systemically administered drugs that might otherwise be hampered in vivo by a number of factors, such as rapid elimination by the kidneys. Mobile, nontoxic PEG chains can be conjugated to biotherapeutics, increasing their hydrodynamic volume, which can in turn prolong their plasma retention time, increase their solubility, and shield antigenic determinants on the drug from detection by the immune system. Attaching PEG molecules for optimal pharmacokinetics without obstructing the active sites that are essential for drug efficacy is a major challenge in pegylation. Current pegylation technology uses linkerless conjugation methods to produce coupling without added toxicity or immunogenicity, and may keep the innate surface charge of the pegylated molecule intact. In addition to controlling the size and complexity of PEG molecules, the attachment site can be manipulated to avoid steric hindrance of the drug's active receptor-recognition or substrate-interaction site. A few pegylated drugs have been engineered to have an improved pharmacokinetic profile with preserved bioactivity. They often have prolonged steady plasma concentrations in vivo, thereby making a reduced number of doses possible. Other interesting effects have also emerged, such as the self-regulating pharmacokinetics of pegfilgrastim, a pegylated version of the granulocyte colony-stimulating factor filgrastim that is administered for management of chemotherapy-induced neutropenia.
PEGylation can improve performance and dosing convenience of peptides, proteins, antibodies, oligonucleotides and many small molecules by optimizing pharmacokinetics, increasing bioavailability, and decreasing immunogenicity and dosing frequency. PEGylation also can increase therapeutic efficacy by enabling increased drug concentration, improved biodistribution, and longer dwell time at the site of action. As a result, therapeutic drug concentrations can be achieved with less frequent dosing—a significant benefit to patients who are taking injected drugs.
When attached to a drug, polyethylene glycol (PEG) polymer chains can sustain bioavailability by protecting the drug molecules from immune responses and other clearance mechanisms. In an aqueous medium, the long, chain-like PEG molecule is heavily hydrated and in rapid motion. This motion causes the PEG to sweep out a large volume and prevent the interference of other molecules.

The improved dosing schedule, with longer intervals between administrations of the pegylated agents, will improve compliance and quality of life in patients with chronic disease.

The downside of working with the lowest bidder however is that PEGylation of proteins is known for its suboptimal yields; losses of 20-40% of precious protein and PEG-agent are not uncommon. Comapnies with cutting edge but more expensive technology can help to significantly improve the yield of PEGylation processes in a fast and efficient manner. However with the growin demand for such technology, its takes a long time to get an order back.
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