PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies
PEGylated nanomedicines are known to induce infusion reactions (IRs) that in some cases can be life-threatening. Herein, we report a case study in which a patient with rare mediastinal and intracardiac IgG4-related sclerosing disease received 8 treatments of intravenously administered PEGylated lipo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/3/558 |
| _version_ | 1819001085121003520 |
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| author | Yaelle Bavli Bing-Mae Chen Steve R. Roffler Marina A. Dobrovolskaia Eldad Elnekave Shifra Ash Yechezkel Barenholz Keren Turjeman |
| author_facet | Yaelle Bavli Bing-Mae Chen Steve R. Roffler Marina A. Dobrovolskaia Eldad Elnekave Shifra Ash Yechezkel Barenholz Keren Turjeman |
| author_sort | Yaelle Bavli |
| collection | DOAJ |
| description | PEGylated nanomedicines are known to induce infusion reactions (IRs) that in some cases can be life-threatening. Herein, we report a case study in which a patient with rare mediastinal and intracardiac IgG4-related sclerosing disease received 8 treatments of intravenously administered PEGylated liposomal methylprednisolone-succinate (NSSL-MPS). Due to the ethical requirements to reduce IRs, the patient received a cocktail of premedication including low dose of steroids, acetaminophen and H2 blockers before each infusion. The treatment was well-tolerated in that IRs, complement activation, anti-PEG antibodies and accelerated blood clearance of the PEGylated drug were not detected. Prior to the clinical study, an in vitro panel of assays utilizing blood of healthy donors was used to determine the potential of a PEGylated drug to activate complement system, elicit pro-inflammatory cytokines, damage erythrocytes and affect various components of the blood coagulation system. The overall findings of the in vitro panel were negative and correlated with the results observed in the clinical phase. |
| first_indexed | 2024-12-20T22:43:36Z |
| format | Article |
| id | doaj.art-a4a5ff46d1924662b5c3171c0b42336f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-20T22:43:36Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a4a5ff46d1924662b5c3171c0b42336f2022-12-21T19:24:25ZengMDPI AGMolecules1420-30492020-01-0125355810.3390/molecules25030558molecules25030558PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical StudiesYaelle Bavli0Bing-Mae Chen1Steve R. Roffler2Marina A. Dobrovolskaia3Eldad Elnekave4Shifra Ash5Yechezkel Barenholz6Keren Turjeman7Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 9112102, IsraelInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanNanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USADavidoff Cancer Institute, Rabin Medical Center, Petach Tikva 4941492, IsraelRina Zaizov Pediatric Hematology Oncology Division, Schneider Children’s Medical Center of Israel, Petach Tiqva, Tel Aviv University, Tel Aviv, Israel 4920235, IsraelLaboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 9112102, IsraelLaboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 9112102, IsraelPEGylated nanomedicines are known to induce infusion reactions (IRs) that in some cases can be life-threatening. Herein, we report a case study in which a patient with rare mediastinal and intracardiac IgG4-related sclerosing disease received 8 treatments of intravenously administered PEGylated liposomal methylprednisolone-succinate (NSSL-MPS). Due to the ethical requirements to reduce IRs, the patient received a cocktail of premedication including low dose of steroids, acetaminophen and H2 blockers before each infusion. The treatment was well-tolerated in that IRs, complement activation, anti-PEG antibodies and accelerated blood clearance of the PEGylated drug were not detected. Prior to the clinical study, an in vitro panel of assays utilizing blood of healthy donors was used to determine the potential of a PEGylated drug to activate complement system, elicit pro-inflammatory cytokines, damage erythrocytes and affect various components of the blood coagulation system. The overall findings of the in vitro panel were negative and correlated with the results observed in the clinical phase.https://www.mdpi.com/1420-3049/25/3/558pegylated nanodrugshypersensitive reactionsanti-peg antibodiescomplement activationliposomal steroidsigg4 related disease |
| spellingShingle | Yaelle Bavli Bing-Mae Chen Steve R. Roffler Marina A. Dobrovolskaia Eldad Elnekave Shifra Ash Yechezkel Barenholz Keren Turjeman PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies Molecules pegylated nanodrugs hypersensitive reactions anti-peg antibodies complement activation liposomal steroids igg4 related disease |
| title | PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies |
| title_full | PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies |
| title_fullStr | PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies |
| title_full_unstemmed | PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies |
| title_short | PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies |
| title_sort | pegylated liposomal methyl prednisolone succinate does not induce infusion reactions in patients a correlation between in vitro immunological and in vivo clinical studies |
| topic | pegylated nanodrugs hypersensitive reactions anti-peg antibodies complement activation liposomal steroids igg4 related disease |
| url | https://www.mdpi.com/1420-3049/25/3/558 |
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