Inhibition of Liposome-Induced Complement Activation by Incorporated Poly(Ethylene Glycol)-Lipids
| Autor: | Donald E. Brooks, Johan Janzen, Steven M. Ansell, Dana V. Devine, Amanda J. Bradley |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Biophysics
Biochemistry Polyethylene Glycols Classical complement pathway chemistry.chemical_compound In vivo PEG ratio Humans Complement Pathway Classical Particle Size Molecular Biology Complement Inactivator Proteins Drug Carriers Liposome Chemistry Complement C1q Phosphatidylethanolamines Complement system Molecular Weight Antibody opsonization Cholesterol Liposomes Drug carrier Ethylene glycol Protein Binding |
| Zdroj: | Archives of Biochemistry and Biophysics. 357:185-194 |
| ISSN: | 0003-9861 |
| DOI: | 10.1006/abbi.1998.0798 |
| Popis: | Complement activation causes opsonization of foreign particles leading to particle elimination from the blood. Complement-mediated opsonization of charged and large liposomes presents a fundamental problem in their use to deliver therapeutic agents in vivo. To prolong the circulation half-lives of such liposomes, complement activation must be curtailed. The aim of this study was to assess the ability of poly(ethylene glycol)-lipids (PEG-lipids) to inhibit the in vitro activation of the classical pathway of complement in human serum by anionic liposomes. Incorporation of cholesterol-PEG600 (CH-PEG600), cholesterol-PEG1000 (CH-PEG1000), or phosphatidylethanolamine-PEG2000 (PE-PEG2000) resulted in dose-dependent inhibition of C1q binding and complement activation. The dose of PEG-lipid at which complement activation was blocked was inversely related to the PEG chain length. Complement activation was strongly inhibited when 15 mole% of CH-PEG600, 10 mole% CH-PEG1000, or 5 mole% PE-PEG2000 was incorporated into 100-nm anionic liposomes. PEG-lipid incorporation into larger liposomes (240 nm) was also successful in blocking C1q binding and complement activation. Radiolabeled cholesterol-PEG approximately 1400 was prepared and used to determine both the percentage of CH-PEG incorporated into the liposomes and the percentage maintained in the liposomes in the presence of 50% human serum at 37 degrees C for up to 24 h. |
| Databáze: | OpenAIRE |
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