PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies

Autor: Bing-Mae Chen, Marina A. Dobrovolskaia, Yechezkel Barenholz, Eldad Elnekave, Shifra Ash, Yaelle Bavli, Steve R. Roffler, Keren Turjeman
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Drug
Male
media_common.quotation_subject
Pharmaceutical Science
Pharmacology
hypersensitive reactions
Intracardiac injection
Article
Analytical Chemistry
Polyethylene Glycols
lcsh:QD241-441
03 medical and health sciences
0302 clinical medicine
IgG4 related disease
lcsh:Organic chemistry
In vivo
Drug Discovery
medicine
Humans
Immunologic Factors
Methylprednisolone Hemisuccinate
liposomal steroids
Physical and Theoretical Chemistry
anti-PEG antibodies
030304 developmental biology
media_common
030203 arthritis & rheumatology
Inflammation
0303 health sciences
complement activation
biology
business.industry
Organic Chemistry
Complement System Proteins
In vitro
Complement system
Acetaminophen
Chemistry (miscellaneous)
Liposomes
biology.protein
PEGylated nanodrugs
Molecular Medicine
Premedication
Female
Disease Susceptibility
Antibody
business
Biomarkers
medicine.drug
Zdroj: Molecules
Volume 25
Issue 3
Molecules, Vol 25, Iss 3, p 558 (2020)
ISSN: 1420-3049
DOI: 10.3390/molecules25030558
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: