PEG for Drugs and Drug Delivery Systems

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Polyethylene Glycol (PEG) Drugs and Drug Delivery
Systems
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What is Polyethylene Glycol (PEG)
TABLE OF CONTENTS
PEG Synthesis Strategies
PEGylation Strategies
Quantitative Analysis Techniques for PEG
Application of PEGylation Derivatives
Marketed PEGylated Products
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What is Polyethylene Glycol (PEG) ?

• Definition
• Polyethylene glycol (PEG), a compound composed of
  repeated ethylene glycol units -(CH2CH2O)n, is
  also known as Macrogol.
• Characteristics
• High structure flexibility
• Biocompatibility
• Amphiphilicity
• Good moisture retention
• Excellent lubricity

Introduction of Polyethylene Glycol
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PEG Synthesis Strategies
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PEGylation Strategies
PEGylation of Peptides and Proteins The activated
PEG achieves coupling through chemical reactions
with the amino acid residues on the peptide or
protein molecules.
PEGylation of Small Molecule Drugs To date, many
organic small molecule drugs have gradually the
PEGylation technology, and certain progress has
been made.
PEGylation of Nanocarriers Due to differences in
the chemical make-up, strategies used for
PEGylation of nanocarriers can be broadly
classified as polymeric nanoparticles, liposomes,
micelles, and inorganic nanoparticles.
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PEGylation of Peptides and Proteins

• PEGylation of Peptide and Protein Strategies
• Site-selective PEGylation
• Enzymatic PEGylation
• Releasable and non-covalent PEGylation

Journal of Controlled Release. 2014, 192 6781.
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PEGylation of Nanocarriers
Due to differences in the chemical make-up,
strategies used for PEGylation of nanocarriers
can be broadly classified as polymeric
nanoparticles, liposomes, micelles, and inorganic
nanoparticles. Polymeric nanoparticles and
inorganic nanoparticles are promising tools for
controlled drug delivery or imaging in cancer
therapy and many other applications.
Progress in Natural Science Materials
International. 2019, 29(6) 612-616.
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PEGylation of Small Molecule Drugs

• Branched PEG
• The Umbrella-like structure provides more binding
  sites and a larger molecular volume.
• Forked PEG 
• Multiple proximal reactive groups are provided at
  one or both ends of the linear PEG chain to
  enhance the drug loading of PEG.
• Multi-armed PEG
• The star-like structure of multi-armed PEG and
  multiple hydroxyl groups greatly advance active
  sites for drug conjugation.

Progress in Polymer Science. 2013, 38 421444.
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Quantification Analytical Techniques for PEG
Method Analysis Content
High-Performance Liquid Chromatography (HPLC) The amount of PEG associated with colloidal carriers
Enzyme-linked Immunosorbent Assay (ELISA) The concentration of PEGylated proteins in serum samples
Colorimetric Assays The concentration and localization of PEG chains
Gas Chromatography (GC) The amount of attached PEG polymer
Mass Spectrometry (MS) The molecular mass of PEGylated species
Liquid Chromatography Mass Spectrometry (LC-MS) The molecular mass of PEGylated species
Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDIMS) The average molecular weight of PEGylated species and degree of PEGylation
Electrospray Ionization Mass Spectrometry (ESI-MS) The average molecular weight of PEGylated species and degree of PEGylation
X-Ray Photoelectron Spectroscopy (XPS) Changes in elemental composition on the conjugate surface before and after PEGylation
Raman Spectroscopy Determination of PEG content and conformation
Thermogravimetric Analysis (TGA) The content of PEG
Inductively Coupled Plasma Mass Spectrometry (ICP-MS) The quantitative measurement of metal-containing PEGylated pharmaceuticals or nanoparticles
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Application of PEGylation Derivatives
Example of PEG Conjugates of Low Molecular Weight
Anticancer Drugs

• Most of the PEG conjugates of low molecular
  weight drugs that have entered clinical trials
  are of the camptothecin family, namely
  camptothecin itself, SN38 and irinotecan.
• PEG-Camptothecin
• PEG-SN38
• PEG-Irinotecan
• PEG-Docetaxel
• PEG-Paclitaxel

Tissue Engineering
Drug Preparation
Drug Delivery
Imaging Diagnosis
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Marketed PEGylated Products
Brand Name Company Indication Comment
Adagen Enzon Severe combined immunodeficiency disease (SCID) PEGylated adenosine deaminase
Cimzia Nektar/UCB Pharma Rheumatoid arthritis and Crohn's disease PEGylated Fab' fragment of a humanized TNF inhibitor monoclonal antibody
Doxil/Caelyx Ortho Biotech/ Schering-Plough Cancer PEGylated liposome of doxorubicin
Macugen Pfizer Neovascular age-related macular degeneration Pegylated anti-vascular endothelial growth factor (VEGF) aptamer
Mircera Roche Anemia associated with chronic kidney disease PEGylated erythropoetin
Neulasta Amgen Chemotherapy-induced neutropenia PEGylated recombinant methionyl human granulocyte colony-stimulating factor
Omontys Affymax/Takeda Pharmaceuticals Anemia associated with chronic kidney disease PEGylated synthetic peptide analog of erythropoietin
Oncaspar Enzon Acute lymphoblastic leukemia PEGylated L-asparaginase
PEGASYS Hoffmann-La Roche Hepatitis B and hepatitis C PEGylated interferon alpha
Pegintron Schering-Plough/Enzon Hepatitis B and hepatitis C PEGylated interferon alpha
Pegloticase Savient Gout PEGylated uricase
Somavert Pfizer Acromegaly PEGylated human growth hormone mutein antagonist
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