title: Modulating antibody pharmacokinetics using hydrophilic polymers.
abstract: BACKGROUND
  The use of hydrophilic polymers as a substitute for the Fc-domain in immuno- or non-immuno-based binding proteins is accelerating. Chemical PEGylation has led the way and is still the most advanced and clinically-approved approach. Hydrophilic polymers act by maintaining a flexible conformation and hydrogen bonding to a network of water molecules to acquire a larger hydrodynamic volume and apparent mass than their actual molecular mass suggest. The benefits are increased blood half-life and bioavailability, stability and reduced immunogenicity. In the case of PEG, there is also evidence of enhanced targeting and reduced side effects, but drawbacks include the fact that PEG is non-biodegradable.
  
  
  METHODS
  This report reviews the state of the art for antibody PEGylation in terms of approaches and effects. Additionally, non-biological (such as N-(2-hydroxypropyl)methacrylamide) and potentially superior biological alternatives (such as polysialylation) are described, ending with recombinant approaches (such as hydrophilic peptides and glyco-engineering), which promise to circumvent the need for chemical modification altogether.
  
  
  CONCLUSIONS
  The emergence of many small, antibody fragment-like mimics will drive the need for such technologies, and PEGylation is still the choice polymer due to its established use and track record. However, there will be a place for many alternative technologies if they can match the pharmacokinetics of PEG-conjugates and bring addition beneficial features such as easier production.
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, UK.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Antony
authors.initials: A
authors.lastname: Constantinou
authors.forename: Mahendra
authors.initials: M
authors.lastname: Deonarain
mesh_terms: D000178:Acrylamides / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D006031:Glycosylation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D012794:Sialic Acids / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000178:Acrylamides; D000911:Antibodies, Monoclonal; D003911:Dextrans; D007128:Immunoglobulin Fragments; D011108:Polymers; D011994:Recombinant Proteins; D012794:Sialic Acids; D011092:Polyethylene Glycols; C032976:N-(2-hydroxypropyl)methacrylamide