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Effect of mannose density on mannose receptor-mediated cellular uptake of mannosylated O/W emulsions by macrophages.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2006 Aug 28; Vol. 114 (2), pp. 193-201. Date of Electronic Publication: 2006 May 09. - Publication Year :
- 2006
-
Abstract
- Carbohydrate grafted emulsions are one of the most promising cell-specific targeting systems for lipophilic drugs. We have previously reported that mannosylated (Man-) emulsions composed of soybean oil, EggPC and cholesten-5-yloxy-N-(4-((1-imino-2-d-thiomannosylethyl)amino)alkyl)formamide (Man-C4-Chol) with a ratio of 70:25:5 were significantly delivered to liver non-parenchymal cells (NPC) via mannose receptor-mediated mechanism after intravenous administration in mice. Since the efficient targeting through a receptor-mediated mechanism is largely controlled by ligand-receptor interaction, the effect of mannose density on Man-emulsions was studied with regard to both the disposition in vivo in mice and the uptake in vitro, using elicited macrophages which express a number of mannose receptors. After intravenous injection, Man-emulsions with 5.0% (Man-5.0-emulsions) and 7.5% (Man-7.5-emulsions) of Man-C4-Chol were rapidly eliminated from the blood circulation and preferentially accumulated in the liver-NPC compared with Man-emulsions with 2.5% of Man-C4-Chol (Man-2.5-emulsions) and bare emulsions (Bare-emulsions). The in vitro study showed increased internalization of Man-5.0- and Man-7.5-emulsions and significant inhibition of uptake in the presence of mannan. The enhanced uptake of Man-emulsions was related to the increasing of Man-C4-Chol content that corresponded to confocal microscopy study. These results suggest that the mannose density of Man-emulsions plays an important role in both cellular recognition and internalization via a mannose receptor-mediated mechanism.
- Subjects :
- Animals
Area Under Curve
Chemical Phenomena
Chemistry, Physical
Dose-Response Relationship, Drug
Emulsions
Injections, Intravenous
Liver cytology
Liver metabolism
Mannose Receptor
Mice
Mice, Inbred ICR
Microscopy, Confocal
Lectins, C-Type chemistry
Macrophages metabolism
Mannose chemistry
Mannose pharmacokinetics
Mannose-Binding Lectins chemistry
Receptors, Cell Surface chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0168-3659
- Volume :
- 114
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 16876282
- Full Text :
- https://doi.org/10.1016/j.jconrel.2006.04.010