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 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.
Competing Interests: Yechezkel Barenholz is an inventor of two patents on NSSL-MPS owned by Yissum TTO of the Hebrew University. Yechezkel Barenholz, Yaacov Naparstek, Yuval Avnir and Rina Ulmansky: “The use of Liposomal Glucocorticoids for Treating Inflammatory States.” US Patent 7,744,920, 2010, June 29, 2010 and Yechezkel Barenholz, Alberto A. Gabizon and Yuval Avnir: “Liposomal Compositions of Glucocorticoid and Glucocorticoid Derivatives”. US Patent 8,932,627, January 13, 2015. These 2 granted patents were not yet licensed.The other authors declare no competing interests.