15. anti fouling surfaces
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Anti-Fouling/Non-Fouling Surfaces
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When is the non-specific adsoptionundesirable?
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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 polymersGas discharge deposited coating.
Tetraglyme, PEG Surfactants, Vinyl (EG)2
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Non-Fouling Surface CompositionsNatural 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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Non-Fouling Surface Compositions
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Where did the idea of PEGlyatingsurfaces come from?
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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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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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How does the PEGs Work?PEGylation increases the half-life of the biomolecule in the body via
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Reducing Kidney Filtration
•PEGylation significantly increases the apparent size of the conjugated drug compound
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Method for the activation of PEG molecules
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Conjugation Chemistry
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Conjugation Chemistry
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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
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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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Are There Special Properties to PEG That are Important to its ActionAs a Non-Fouling Surface Composition?
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DSC showing two endothermic peaksAfter 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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How to Immobilize PEG on Surfaces
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Nagaoka et al 1983
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Is there a critical MW below which PEG loses its anti-fouling character?
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Protein(Radius R)
Water
End-on attachedPEG chains(length l)
D
Model by Jeon et al.
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Gombotz and Hoffman 1993
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How can one get a high surface density of PEGs if they have anExcluded volume and repel each other?
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“Glyme” Coatings
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