Immunogenicity and pharmacokinetic attributes of poly(ethylene glycol)-grafted immunoliposomes
| Autor: | Jennifer A. Harding, Samuel Zalipsky, Charles Engbers, Mary S. Newman, Neil I. Goldstein |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Biophysics Enzyme-Linked Immunosorbent Assay Biochemistry Antibodies Polyethylene Glycols Rats Sprague-Dawley chemistry.chemical_compound Immunoglobulin Fab Fragments Mice Drug Delivery Systems Pharmacokinetics Phosphatidylcholine Immunoliposome Tumor Cells Cultured Animals Humans Polyethylene glycol (PEG) Liposome biology Immunoliposomes Immunogenicity Phosphatidylethanolamines Antibodies Monoclonal Cell Biology Flow Cytometry Molecular biology Rats ErbB Receptors chemistry Polyclonal antibodies Drug delivery Liposomes biology.protein Ethylene glycol |
| Zdroj: | Biochimica et biophysica acta. 1327(2) |
| ISSN: | 0006-3002 |
| Popis: | Immunoliposomes composed of hydrogenated soy phosphatidylcholine, cholesterol, methoxypoly(ethylene glycol)-distearoyl phosphatidylethanolamine (mPEG-DSPE), and hydrazide-PEG-DSPE (mole ratio, 57:38:3.3:1.7) linked to periodate-oxidized chimerized mouse IgG (C225, anti-human epidermal growth factor receptor) were prepared by an optimized aggregation-free procedure. The antigen-binding activity of the immunoliposomes was well preserved. When injected intravenously into naive rats, the immunoliposomes (approximately 18 IgG per 100 nm liposome) exhibited long circulation times (MRT = 8.5 h, Cl = 0.2 ml/h). Subsequent injections of the immunoliposomes into the same animals resulted in rapid clearance (MRTor = 0.7 h, Clor = 7 ml/h), which was accompanied by a significant increase in anti-C225 specific titers. Upon repeated injection or coinjection with the parent liposomes free C225 consistently exhibited prolonged circulation without any increase in C225-specific antisera, but was cleared quickly when administered into animals that had been pretreated with the immunoliposomes. Screening of the immunoliposome induced antisera against human polyclonal IgG and C225-derived Fab' fragment revealed that the immune response was specifically triggered by the constant human region of C225. These results demonstrate that the preparations of PEG-grafted immunoliposomes are more immunogenic than the free IgG component, which is of profound importance to the antibody-mediated liposomal drug delivery effort. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|