Applications of Polyethyleneimine in the Biopharmaceutical Industry
Time：2024-03-12 Hits：163
Polyethyleneimine (PEI), also referred to as polyaziridine, is a water-soluble and highly charged polymer composed of monomer chains (-CH2CH2NH-). The surface of PEI is rich in amino groups and carries positive charges in nearly neutral solutions. Its surface can undergo various chemical modifications such as acetylation, carboxylation, hydroxylation, polyethylene glycol (PEG) conjugation, oligosaccharide attachment, fluorescent labeling, and more, resulting in a diversified range of functions.
PEI exhibits two structural forms: linear and branched. Linear PEI, derived from the acidic hydrolysis of polyoxazolines, features only secondary amines, making it challenging to obtain low-molecular-weight linear PEI. Both primary and secondary amines in PEI are active, with strong nucleic acid binding capabilities, serving as essential components in targeting reagents, drugs, etc. On the other hand, tertiary amines, while having weaker binding abilities, act as buffering agents in acidic conditions. Notably, dendritic PEI is typically in liquid form, while linear PEI is solid at room temperature and insoluble in cold water, phenol, ethyl ether, and other solvents. Its solubility increases in hot water and organic solvents such as methanol, ethanol, and chloroform.
Key Characteristics:
High Adhesion and Adsorption: Amino groups in PEI can form hydrogen bonds with carboxyl groups and react to create ionic or covalent bonds. With both hydrophilic (amino group) and hydrophobic (vinyl group) components, PEI can bind extensively to different substances. This characteristic finds applications in adhesives, inks, coatings, and various adhesive-related fields.
High Cationicity: In water, PEI exists as a polymer cation, capable of neutralizing and adsorbing anionic substances and chelating heavy metal ions. Its high cationicity makes it valuable in papermaking, water treatment, electroplating solutions, and as dispersants.
High Reactivity: PEI features highly reactive primary and secondary amines that readily react with epoxy, acids, isocyanate compounds, and acidic gases. This reactivity makes PEI suitable for applications such as an epoxy resin modifier, aldehyde adsorbent, and color-fixing agent.
Application Resolutions:
Branched PEI is widely utilized, while linear PEI primarily serves as a eukaryotic cell gene transfection vector.
Synthesis of Branched PEI: Ethyleneimine is the primary raw material used to synthesize branched polyethyleneimine.
Synthesis of Linear PEI: Oxazole derivatives serve as raw materials in the synthesis of linear polyethyleneimine.
Polyethyleneimine (PEI), as an engineering plastic, finds widespread applications across diverse industries such as electronic appliances, automobiles, aerospace, machinery, the food industry, medical equipment, papermaking, water treatment, detergents, adhesives, cosmetics, and particularly in the biopharmaceutical field with a focus on non-viral gene vectors.
1) Application in Gene Carriers:
PEI serves as a polycationic non-viral gene carrier, leveraging its unique molecular structure with protonatable amino nitrogen atoms. The "proton sponge effect" allows PEI to absorb protons in acidic endosome environments, increasing osmotic pressure, causing membrane instability, and facilitating the escape of engulfed complexes to prevent DNA degradation. PEI, a significant polymer transfection reagent, exhibits enhanced transfection efficiency with higher molecular weights (typically above 20,000), although cytotoxicity also increases. Strategies such as linking linear or multi-branched PEI to biodegradable bonds, like ester, carbon-nitrogen double, or disulfide bonds, mitigate cytotoxicity while maintaining transfection activity. Grafting small molecule PEI onto polymer skeletons further enhances transfection efficiency and reduces cytotoxicity. Incorporating targeting substances, such as ligands, carbohydrates, and antibodies, allows for cell-specific gene delivery.
2) Application in Immobilized Enzymes:
PEI, with numerous amino groups along its macromolecular chain, acts as a positively charged polyelectrolyte suitable for immobilized enzyme technology. By bonding to a carrier, PEI provides amino covalent enzyme points and electrostatically adsorbs negatively charged enzymes, facilitating their immobilization. Using PEI as a functional branch carrier enhances the interaction between enzymes and carriers, increasing adsorption capacity, binding force, and adsorption stability. This ensures that the immobilized enzymes maintain high catalytic activity for repeated use.
3) Application in Drug Delivery:
PEI's multi-level amine structure enables effective compression and encapsulation of proteins or genetic drugs, making it a gold standard for evaluating transfection effects in polymer drug carriers. The positive surface charge of PEI facilitates interactions with cell membranes, aiding in the delivery of proteins or genes into cells.
4) Application in Immune Adjuvants:
PEI exhibits strong adjuvant activity, making it a potential vaccine adjuvant to enhance the effects of traditional vaccines against infections and tumors. Certain vaccines based on PEI have progressed to clinical research stages, requiring careful selection of PEI types, antigens, construction strategies, and immune pathways.
5) Application in Protein Separation:
As a positively charged polymer, PEI binds to negatively charged macromolecules, such as acidic proteins and nucleic acids, forming a PEI network structure that precipitates as a complex for rough separation.
6) Application in Biomarkers:
Conjugating PEI with imaging agents allows it to function as a biomarker reflecting specific cellular or subcellular information, including cell migration, under specific conditions.
PEI and Derivative Products:
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Product name
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Molecular weight
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Package
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Linear polyethylenimine
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25000,4000
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100mg, 500mg
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Polyethylenimine, Linear
|
||
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Polyethyleneimine-polyethylene glycol
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PEG：1000,2000,3400,5000,10k
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100mg, 500mg
|
|
PEI-PEG
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PEI: 600, 1800, 3000, 10k, 25k, 70k
|
|
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Polyethyleneimine-polyethylene glycol-azide
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PEG：1000,2000,3400,5000,10k
|
100mg, 500mg
|
|
PEI-PEG-N3
|
||
|
Polyethyleneimine-polyethylene glycol-mercapto
|
PEG：1000,2000,3400,5000,10k
|
100mg, 500mg
|
|
PEI-PEG-SH
|
||
|
Polyethyleneimine-polyethylene glycol-maleimide
|
PEG：1000,2000,3400,5000,10k
|
100mg, 500mg
|
|
PEI-PEG-MAL
|
||
|
Methoxypolyethylene glycol-polyethyleneimine
|
PEG：1000,2000,5000
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500mg,1g
|
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mPEG-PEI
|
||
|
Polyethylenimine-polyethylene glycol-biotin
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PEG：1000,2000, 3400,5000,10k
|
100mg, 500mg
|
|
PEI-PEG-Biotin
|
||
|
Polyethylenimine-polyethylene glycol-fluorescein
|
PEG：1000,2000, 3400,5000,10k
|
100mg, 500mg
|
|
PEI-PEG-FITC
|
||
|
Polyethylenimine-hyaluronic acid
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HA：2000,3000,5000,7000,10k
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100mg, 500mg
|
|
PEI-Hyaluronate
|
||
|
Polyethyleneimine polylactic acid glycolic acid copolymer
|
PEI branched chain type, MW:800
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100mg, 500mg
|
|
PEI-PLGA,PLGA 50/50
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PLGA:5000,30000,6000
|
|
|
Dipalmitoylphosphatidylethanolamine-polyethylenimine
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PEI: 1200,1800,2000,3400,5000,25k
|
100mg, 500mg
|
|
DSPE-PEI
|
||
|
Polyethylene imine polyethylene glycol phospholipid
|
PEG：1000,2000, 3400,5000,10k
|
100mg, 500mg
|
|
PEI-PEG-DSPE
|
||
|
polyethyleniminepolylysine
|
|
100mg, 500mg
|
|
PEI-PLL
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