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Polyethylene Glycol (PEG ) Drugs and Drug Delivery
Systems
TABLE OF CONTENTS What is Polyethylene Glycol (PEG) PEG Synthesis Strategies
PEGylation Strategies
04 02 03 01
05
Quantitative Analysis Techniques for PEG
Application of PEGylation Derivatives
06 Marketed PEGylated Products
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
PEG Synthesis Strategies
PEGylation Strategies
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 Peptides and Proteins
The activated PEG achieves coupling through chemical reactions with the amino acid residues on the peptide or protein molecules.
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.
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: 67–81.
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.
Nanoparticles
Nanoparticles reserved various
advantages for drug delivery, such as controlled release and targeting. The introduction of PEG will not only affect the biodegradation behavior of
nanoparticles but also the release and
distribution of drugs in the body.
Progress in Natural Science: Materials International. 2019, 29(6): 612-616.Liposomes
Liposome is an ideal drug delivery carrier due to its targeted properties, longer blood retention time, and higher organ distribution selectivity, which can improve the efficacy of drugs and reduce toxic side effects.
Micelles
Micelles are frequently the preferred choice for anticancer drug delivery. Preparation of PEGylated micelles mostly utilizes PEGylated polymers or lipids through synthetic
approaches.
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, 38:421–444.
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 (MALDI–MS) 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
Application of PEGylation Derivatives
Drug Delivery Imaging
Diagnosis
Tissue Engineering Drug
Preparation 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
Example of PEG Conjugates of Low Molecular
Weight Anticancer Drugs
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
