Table 3. Examples of PEG alternatives and their immunological properties.
Common immunological responses to PEG alternatives include allergy, hypersensitivity reactions and immunogenicity. The information in the table is based on references [61, 267–276, 278–283, 286–288, 294–298]. HSR = hypersensitivity reaction; CARPA = complement activation related pseudoallergy; APTT = activated partial thromboplastin time; HIT = heparin-induced thrombocytopenia; PF4 = platelet factor 4; DC = dendritic cells;
| Polymer | Type of response | Mechanism |
|---|---|---|
| Poly(vinylpyrrolidone) | Anaphylaxis; inhibition of blood coagulation | IgE-mediated activation and degranulation of mast cells’ Prolongation of APTT; inhibition of coagulation factor VIII; |
| Poly(sorbate) | HSR; anaphylactoid reactions (CARPA); true anaphylaxis | Complement activation; IgE-mediated mast cell degranulation; basophil activation |
| Poly(glycerol) | Allergic contact dermatitis | unknown |
| Poly(docanol) | Allergic contact dermatitis, skin sensitization | unknown |
| Poly(oxazoline) | Inhibition of blood coagulation | Prolongation of APTT |
| Poly(2-methyl-2-oxazoline) (PMOXA) | Pseudoallergy; increased uptake by phagocytes | Complement activation; opsonization; induction of polymer-specific IgM |
| Poly(acrylamide) | Contact dermatitis to monomer components | unknown |
| Poly(N-acryloyl morpholine) | Skin sensitization by monomers | unknown |
| Poly(sialic) acid | Immunogenicity Monomers inhibit complement and phagocytosis Monomers enhance allergy |
Unknown Binding to complement factor H Mast cell degranulation |
| Pro, Ala and Ser (PAS) polypeptide | Potential immunogenicity | Tendency to aggregate |
| Poly(glutamic acid) | Late onset anaphylaxis Adjuvanticity | Polymer specific IgE DC maturation |
| Poly-(carboxybetaine) | Inflammation | Cytokine induction |
| Ala, Asp, Gly, Pro, Ser, and Thr polypeptide (XTEN) | Potential immunogenicity | Tendency to aggregate (though at a less degree than PAS) |
| Heparin | Inhibition of blood coagulation; immunogenicity; HIT; delayed anaphylaxis | Prolongation of APTT; inhibition of coagulation factors; type II antigen; formation of complex with the chemokine PF4 resulting in an irreversible aggregation and depletion of blood platelets |
| Hyaluronic acid | Delayed type hypersensitivity, anaphylaxis and vascular thrombosis | Unknown; in some cases development of these reactions were preceded by viral infections |