Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties

S.M. Moghimi, J. Szebeni

Research output: Contribution to journalArticle

Abstract

his article critically examines and evaluates the likely mechanisms that contribute to prolonged circulation times of sterically protected nanoparticles and liposomes. It is generally assumed that the macrophage-resistant property of sterically protected particles is due to suppression in surface opsonization and protein adsorption. However, recent evidence shows that sterically stabilized particles are prone to opsonization particularly by the opsonic components of the complement system. We have evaluated these phenomena and discussed theories that reconcile complement activation and opsonization with prolonged circulation times. With respect to particle longevity, the physiological state of macrophages also plays a critical role. For example, stimulated or newly recruited macrophages can recognize and rapidly internalize sterically protected nanoparticles by opsonic-independent mechanisms. These concepts are also examined. PEG Poly(ethylene glycol) mPEG Methoxypoly(ethylene glycol) RES Reticuloendothelial system SDS Sodium dodecyl sulfate PAGE Polyacrylamide gel electrophoresis RBC Red blood cell PC Phosphatidylcholine PE Phosphatidylethanolamine HSPC Hydrogenated soy phosphatidylcholine DPPC Dipalmitoylphosphatidylcholine DPPE Dipalmitoylphosphatidylethanolamine DSPE Distearoylphosphatidylethanolamine HIC Hydrophobic interaction chromatography PLA2 Phospholipase A2
Original languageEnglish
Pages (from-to)463-478
Number of pages16
JournalProgress in Lipid Research
Volume42
Issue number6
Publication statusPublished - Nov 2003

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