Size-dependent release of carboxyfluorescein from cetylmannoside-modified liposomes in human plasma.
The interaction of liposomes with human plasma was investigated using 6(5)-carboxyfluorescein (CF) as an aqueous phase marker of cetylmannoside-modified multilamellar vesicles (Man-MLVs) of various sizes. The release of CF decreased with increasing liposome concentration. The time courses of the CF release from Man-MLVs were monitored continuously and were analysed kinetically. The curves were characterized by two phases, the first-order release process and the maximum release, which represent the rate and the extent of CF release, respectively. The increase of liposome size increased the rate of release by 42% and the extent of release by 121%, respectively. These effects of liposome size on the release processes were suggested to result from the size-dependent affinities of liposomes to the human complement system. The assay system of liposomally bound fragments of complement component 3 (C3), such as C3b and/or iC3b, was developed by applying a sandwich enzyme-linked immunospecific assay. The percentage of C3 fragments to total proteins bound to liposomes increased with the size of liposomes and there was a good correlation between the extent of CF release and the percentage of C3 fragments bound. These results indicated that Man-MLVs released entrapped CF via activating the human complement system and the affinity of Man-MLV to complement increased with the size of Man-MLVs in human plasma. These in vitro results suggest the role of complement as an opsonin in the disposition of Man-MLVs in humans.
Faculty of Pharmaceutical Sciences, The University of Tokushima, Japan.
A J
AJ
Ferdous
T
T
Ishida
M
M
Shinohara
H
H
Harashima
H
H
Kiwada
D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005069:Evaluation Studies as Topic; D005452:Fluoresceins / Q000008:administration & dosage*; D005456:Fluorescent Dyes; D006801:Humans; D008081:Liposomes; D008362:Mannosides; D008657:Metabolic Clearance Rate; D010316:Particle Size; D010587:Phagocytosis
D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D008362:Mannosides; C024098:6-carboxyfluorescein; C069589:cetylmannoside