TY - JOUR
T1 - PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients
T2 - A correlation between in vitro immunological and in vivo clinical studies
AU - Bavli, Yaelle
AU - Chen, Bing Mae
AU - Roffler, Steve R.
AU - Dobrovolskaia, Marina A.
AU - Elnekave, Eldad
AU - Ash, Shifra
AU - Barenholz, Yechezkel
AU - Turjeman, Keren
N1 - Publisher Copyright:
© 2020 by the authors.
PY - 2020/1/28
Y1 - 2020/1/28
N2 - 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.
AB - 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.
KW - Anti-PEG antibodies
KW - Complement activation
KW - Hypersensitive reactions
KW - IgG4 related disease
KW - Liposomal steroids
KW - PEGylated nanodrugs
UR - http://www.scopus.com/inward/record.url?scp=85078738730&partnerID=8YFLogxK
U2 - 10.3390/molecules25030558
DO - 10.3390/molecules25030558
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C2 - 32012928
AN - SCOPUS:85078738730
SN - 1420-3049
VL - 25
JO - Molecules
JF - Molecules
IS - 3
M1 - 558
ER -