Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions
Abstract Polysorbate 80 for injection (TW80) is a common excipient used for injection whose macromolecular impurities, including those that cause anaphylactoid reactions, are frequently ignored. The main aim of this study was to prove that the macromolecular impurities in the excipient are an import...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | BMC Pharmacology and Toxicology |
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| Online Access: | https://doi.org/10.1186/s40360-022-00591-5 |
| _version_ | 1828329329715576832 |
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| author | Yue Li Jinlian Duan Heng Xia Yongkun Li Bin Shu Weigang Duan |
| author_facet | Yue Li Jinlian Duan Heng Xia Yongkun Li Bin Shu Weigang Duan |
| author_sort | Yue Li |
| collection | DOAJ |
| description | Abstract Polysorbate 80 for injection (TW80) is a common excipient used for injection whose macromolecular impurities, including those that cause anaphylactoid reactions, are frequently ignored. The main aim of this study was to prove that the macromolecular impurities in the excipient are an important cause of anaphylactoid reactions. Component A (containing macromolecules > 100 kDa), Component B (containing macromolecules from 10 to 100 kDa), and Component C (containing substances < 10 kDa) were prepaired from the original TW80 using ultrafilters. The original TW80 contained numerous substances with molecular weights > 10kD. The original TW80 and Components A and B caused strong anaphylactoid reactions in both guinea pigs and rabbits by intravenous administration. Moreover, the original TW80 and Components A and B even caused strong passive cutaneous anaphylactoid (PCA) reactions and pulmonary capillary permeability. The PCA reaction and increased permeability were partly prevented by cromolyn sodium. Additionally, the original TW80 and Components A and B caused vasodilation and severe hemolysis in vitro. The anaphylactoid reactions were associated with histamine release but not with mast cell degranulation. Nevertheless, Component C almost caused no anaphylactoid reactions or hemolysis and was weaker in the few reactions that ocurred. Taken together, these results suggest that macromolecular substances are one of the main risk factors responsible for anaphylactoid reactions and hemolysis caused by TW80. |
| first_indexed | 2024-04-13T20:22:55Z |
| format | Article |
| id | doaj.art-4a88013b0a874315b3b5899753740df7 |
| institution | Directory Open Access Journal |
| issn | 2050-6511 |
| language | English |
| last_indexed | 2024-04-13T20:22:55Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pharmacology and Toxicology |
| spelling | doaj.art-4a88013b0a874315b3b5899753740df72022-12-22T02:31:28ZengBMCBMC Pharmacology and Toxicology2050-65112022-07-0123111210.1186/s40360-022-00591-5Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactionsYue Li0Jinlian Duan1Heng Xia2Yongkun Li3Bin Shu4Weigang Duan5School of Basic Medicine, Yunnan University of Traditional Chinese MedicineSchool of Basic Medicine, Yunnan University of Traditional Chinese MedicineSchool of Basic Medicine, Yunnan University of Traditional Chinese MedicineSchool of Traditional Chinese Medicine, Yunnan University of Traditional Chinese MedicineJiangsu Center for Safety Evaluation of Drugs, Nanjing Tech UniversitySchool of Basic Medicine, Yunnan University of Traditional Chinese MedicineAbstract Polysorbate 80 for injection (TW80) is a common excipient used for injection whose macromolecular impurities, including those that cause anaphylactoid reactions, are frequently ignored. The main aim of this study was to prove that the macromolecular impurities in the excipient are an important cause of anaphylactoid reactions. Component A (containing macromolecules > 100 kDa), Component B (containing macromolecules from 10 to 100 kDa), and Component C (containing substances < 10 kDa) were prepaired from the original TW80 using ultrafilters. The original TW80 contained numerous substances with molecular weights > 10kD. The original TW80 and Components A and B caused strong anaphylactoid reactions in both guinea pigs and rabbits by intravenous administration. Moreover, the original TW80 and Components A and B even caused strong passive cutaneous anaphylactoid (PCA) reactions and pulmonary capillary permeability. The PCA reaction and increased permeability were partly prevented by cromolyn sodium. Additionally, the original TW80 and Components A and B caused vasodilation and severe hemolysis in vitro. The anaphylactoid reactions were associated with histamine release but not with mast cell degranulation. Nevertheless, Component C almost caused no anaphylactoid reactions or hemolysis and was weaker in the few reactions that ocurred. Taken together, these results suggest that macromolecular substances are one of the main risk factors responsible for anaphylactoid reactions and hemolysis caused by TW80.https://doi.org/10.1186/s40360-022-00591-5Polysorbate 80 for injectionAnaphylactoid reactionsMacromolecular impuritiesCapillary permeabilityPassive cutaneous anaphylactoid reaction |
| spellingShingle | Yue Li Jinlian Duan Heng Xia Yongkun Li Bin Shu Weigang Duan Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions BMC Pharmacology and Toxicology Polysorbate 80 for injection Anaphylactoid reactions Macromolecular impurities Capillary permeability Passive cutaneous anaphylactoid reaction |
| title | Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions |
| title_full | Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions |
| title_fullStr | Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions |
| title_full_unstemmed | Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions |
| title_short | Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions |
| title_sort | macromolecules in polysorbate 80 for injection an important cause of anaphylactoid reactions |
| topic | Polysorbate 80 for injection Anaphylactoid reactions Macromolecular impurities Capillary permeability Passive cutaneous anaphylactoid reaction |
| url | https://doi.org/10.1186/s40360-022-00591-5 |
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