This document discusses non-fouling surfaces, specifically those using polyethylene glycol (PEG) polymers. It describes how PEGylation of drug molecules can increase their circulation time in the body by reducing kidney filtration. PEG is effective because its hydrophilic and flexible properties help form a hydration layer around coated surfaces that prevents non-specific protein adsorption. However, achieving high surface densities of PEG requires methods to overcome the excluded volume effect between tethered polymer chains. The document provides several examples of PEGylated protein drugs that have been approved for medical use.

1. Anti-Fouling/Non-Fouling Surfaces
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3. When is the non-specific adsoption
undesirable?
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7. Non-Fouling Surface Compositions
Synthetic Hydrophilic Surfaces
PEG Polymers, Hydrogels and Adsorbed
Surfactants
PEG, PEG-HG, PEG-PU, Pluronics.
Neutral Polymers: PHEMA; PVP etc.
Phosphoryl Choline Polymers.
Zwitterion polymers
Gas discharge deposited coating.
Tetraglyme, PEG Surfactants, Vinyl (EG)2
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8. Non-Fouling Surface Compositions
Natural Hydrophilic Surfaces
Passivating Protein Monolayers:
Eg: Albumin, Casein.
Polysaccharides:
Eg: Dextran, Hyaluronic Acid.
Glycoproteins:
Eg: Mucins.
Phosphoryl Choline Polymers.
Zwitterion polymers
Liposaccharides:
Eg: Gangliosides. Used as Stealth Liposomes
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9. Non-Fouling Surface Compositions
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10. Where did the idea of PEGlyating
surfaces come from?
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13. The need for PEGylation
The Novel Proteins and Peptides have become important
new drugs with advent of a revolution in Biotechnology.
More than 80 Poly Peptide Drugs are marketed in The
U.S.
More than 350 Proteins and Peptides are
undergoing clinical trails right now.
About a third of Drug candidates in clinical trails are
Poly peptides.
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14. The purpose of PEGylation
To Improve drug solubility
To Reduce dosage frequency, without diminished efficacy with
potentially reduced toxicity
To Extend circulating life
To Increase drug stability
 To Enhance protection from proteolytic degradation
Opportunities for new delivery formats and dosing regimens
 To Extend patent life of previously approved drugs
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15. How does the PEGs Work?
PEGylation increases the half-life of the biomolecule in the body via
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16. Reducing Kidney Filtration
•PEGylation significantly increases the apparent size of the conjugated
drug compound
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17. Method for the activation of PEG molecules
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18. Conjugation Chemistry
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19. Conjugation Chemistry
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20. In Protein Drug Delivery:
 PEGASYS: PEGylated alpha-interferons for use in the treatment of
chronic hepatitis C and hepatitis-B(Hoffman-La Rochen)
ADAGEN: receivedapproval for the treatment of severe combined
immunodeficiency(SCID), a disease associated with an inherited
deficiency of adenosine deaminase36.
 PEG-Intron: PEGylated alpha-interferons for use in the treatment of
chronic hepatitis C and hepatitis B(Schering-Plough / Enzon)
Oncaspar: PEGylated L-asparaginase for the treatment of acute
lymphoblastic leukemia in patients who are hypersensitive to the native
unmodified form of L-asparaginase (Enzon).
 Neulasta: PEGylated recombinant methionyl human granulocyte
colony stimulating factor for severe cancer chemotherapy-induced
neutropenia(Amgen)
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21. Pegfilgrastim (Neulasta), which was approved in 2002, is a pegylated
form of the earlier drug filgrastim (Neupogen). Both contain
recombinant methionyl human G-CSF,which is known as filgrastim.
The drugs stimulate the production of the infection fighting white
blood cells (neutrophils) that are depleted by cancer chemotherapy.
Whereas filgrastim requires daily injections for about 14 days,
pegfilgrastim requires one injection per chemotherapy cycle.
A pegylated form of human growth hormone antagonist called
pegvisomant (Somavert) is being developed for the treatment of
ACROMEGALY.
Pegvisomant has been approved in Europe, and is awaiting FDA
approval in the US.
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22. Are There Special
Properties to PEG That are
Important to its Action
As a Non-Fouling Surface
Composition?
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24. DSC showing two endothermic peaks
After freezing and slowly thawing.
Note that the peaks are sensitive to
The MW of PEG.
Poly(Ethylene Glycol) chemistry:
Biotechnical and Biomedical
Applications, J. M. Harris, Ed., Plenum,
New York, 1992
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25. How to Immobilize PEG on Surfaces
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27. Nagaoka et al 1983
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28. Is there a critical MW below which PEG loses its
anti-fouling character?
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29. Protein
(Radius R)
Water
End-on attached
PEG chains
(length l)
D
Model by Jeon et al.

30. Gombotz and Hoffman 1993
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31. How can one get a high surface
density of PEGs if they have an
Excluded volume and repel
each other?
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35. “Glyme” Coatings
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