Characterization of a mannosylphospholipid liposome system for drug targeting to alveolar macrophages

Abstract

The potential that mannose receptors on alveolar macrophages (AMs) may be targeted using mannose-conjugated liposomes for intracellular drug delivery to AMs was investigated. A mannosylphospholipid was synthesized via the reaction of α-d-mannopyranosylphenylisothiocyanate with dipalmitoyl phosphatidylethanolamine, and the product was identified using thin-layer chromatography and nuclear magnetic resonance spectroscopy. Liposomes containing this mannosylated phospholipid were made using a high-pressure homogenization method and analyzed using freeze-etch electron transmission microscopy. These liposomes were shown to exhibit unilamellar structure with a mean diameter of 140 ± 59 nm. The uptake of liposomes by rat alveolar macrophages, by measurement of internalized, liposome-encapsulated fluorescein, was found to be both dose and time dependent. The uptake of liposomes containing 40% mannosylphospholipid was 3.6-fold higher than that of liposomes without the mannosylated lipid (16% to 4.5%). Fluorescein in solution was not internalized by AMs. The enhancement of uptake by conjugation of mannose onto the liposome surface was markedly inhibited by the addition of free mannose at various concentrations, indicating an uptake process involving mannose receptor—mediated endocytosis.